Novel PAR-2 inhibitor

Abstract

The present invention provides novel compounds of formula (I) and pharmaceutical compositions containing these compounds. The compounds of formula (I) can act as PAR-2 inhibitors, whereby these compounds are very advantageous for use in therapy, particularly in the treatment or prevention of pain, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, central nervous system disorders, spinal cord injuries, metabolic disorders, gastrointestinal disorders, cardiovascular disorders, fibrotic disorders, respiratory disorders, skin disorders, allergic disorders, or cancer. TIFF2025520183000592.tif47114

Description

Technical Field

[0001] The present invention provides novel compounds of formula (I) and pharmaceutical compositions containing these compounds. The compounds of formula (I) can act as PAR-2 inhibitors, whereby these compounds are very advantageous for use in therapy, particularly in the treatment or prevention of pain, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, central nervous system disorders, spinal cord injuries, metabolic disorders, gastrointestinal disorders, cardiovascular disorders, fibrotic disorders, respiratory disorders, skin disorders, allergic disorders, or cancer.

Background Art

[0002] Protease-activated receptor (PAR) family G protein-coupled receptors (GPCRs) form the largest family of human membrane proteins (about 800 members) and are involved in many physiological processes. Compounds targeting GPCRs also account for approximately 27% of the global therapeutic drug market (Hauser et al., Nat. Rev. Drug Discov., 2017, 16(12):829-842).

[0003] Two percent of the human genome encodes proteases (also called proteinases), suggesting their importance in the proper functioning of the body (Hollenberg et al., Br. J. Pharmacol., 2014, 171(5):1180 - 94). Indeed, certain soluble and membrane - bound proteinases have been shown to regulate cell function by cleaving GPCRs at the cell surface, activating or inactivating receptors such as protease - activated receptors (PARs). The PAR family consists of four members (PAR - 1, PAR - 2, PAR - 3 and PAR - 4) and belongs to the class A GPCR receptor subfamily (Macfarlane et al., Pharmacological Reviews, 2001, 475(7357):519 - 23). They are expressed in a wide variety of cells such as platelets, immune cells, endothelial cells, muscle cells, astrocytes, neurons, epithelial cells and fibroblasts and are involved in a number of physiological and pathophysiological functions (Ossovskaya et al., Physiol. Rev., 2004, 84(2):579 - 621). PAR - 2: Mechanism of action Activation of PARs is accompanied by cleavage of the extracellular N - terminal portion of the receptor by a protease at a specific site. This exposes an amino - terminal amino acid sequence that folds and acts as a "tethered ligand" (TL), which binds to a conserved region within the second extracellular loop of the cleaved receptor and induces intracellular signaling (Ossovskaya et al., Physiol. Rev., 2004, 84(2):579 - 621; Hollenberg et al., Br. J. Pharmacol., 2014, 171(5):1180 - 94).

[0004] PAR - 2 is activated by multiple host - and pathogen - derived serine proteases such as trypsin, mast cell tryptase, kallikrein and TF - FVIIa and FVa - FXa, which are members of the coagulation cascade. In humans, these proteases cleave at the R 34 ↓S 35Cleavage with LIGKV exposes the tethered ligand SLIGKV. Artificially, in vitro, the synthetic peptide corresponding to TL(SLIGKV) can activate without cleaving the receptor.

[0005] Activation of PAR-2 is q , G i , and G 12 / 13 induces multiple signaling cascades involving several G proteins such as. The most well-described pathway so far involves its interaction with G q and mobilization of intracellular calcium that affects the function of multiple cell types. After repeated activation, PAR2 is rapidly desensitized via its endocytosis by a β-arrestin-dependent mechanism and its targeting to lysosomes (Ossovskaya et al., Physiol. Rev., 2004, 84(2):579 - 621). PAR-2 in the physiological state PAR-2 has been shown to have major functions in multiple organs (Ossovskaya et al., Physiol. Rev., 2004, 84(2):579 - 621). PAR-2 is expressed in neurons and glial cells in the brain. It is also found in spinal cord afferent neurons and nociceptive DRG neurons in the periphery. PAR-2 signaling is involved in the survival, sensitization and signal transmission of these cells, thereby controlling neuronal damage, inflammation and pain.

[0006] PAR-2 is involved in the function of the cardiovascular system. Indeed, its activation induces relaxation or contraction of some blood vessels such as pulmonary arteries, coronary arteries and intramyocardial arteries, and thus can regulate blood flow. It also controls endothelial inflammation and repair that affect vascular permeability.

[0007] PAR-2 expression has been detected in the small intestine, colon, liver, pancreas, and stomach within the gastrointestinal system. Its activation is involved in the regulation of ion transport from the intestinal mucosa, contraction of the gastric longitudinal muscle, secretion of pancreatic juice, saliva, and gastric juice, excitation of enteric muscle neurons, integrity of the intestinal barrier, and release of prostaglandins from intestinal cells. Therefore, PAR-2 plays a major role in the control of body fluid secretion, intestinal inflammation, and gastrointestinal hyperalgesia.

[0008] Since PAR-2 is expressed by epithelial and endothelial cells in the lung, it is involved in airway function. Its activation has been shown to regulate bronchodilation or bronchoconstriction (depending on the experimental system used), ion transport in the airway epithelium, and proliferation and activation of airway smooth muscle cells and lung fibroblasts. Therefore, PAR-2 may regulate airway resistance, lung inflammation, and pulmonary fibrosis.

[0009] In the skin, PAR-2 expression has been detected in keratinocytes, the microvascular system, and immune cells. Its activation is involved in skin pigmentation, skin inflammation, and wound healing.

[0010] Finally, PAR-2 expression has been detected in immune cells such as macrophages, where it affects cell maturation and cytokine secretion, thereby regulating inflammation. PAR-2 in disease states Since PAR-2 regulates numerous and diverse biological processes, it is not surprising that its dysfunction is involved in an equal number of disease states.

[0011] PAR-2 is expressed in the brain, dorsal root ganglia, spinal cord sensory neurons, and nociceptive DRG neurons. Its activation by proteases such as tryptase released by mast cells leads to calcium and cAMP signaling (Steinhoff et al., Nat Med, 2000, 6(2):151-158; Zhao et al., J Biol Chem., 2015, 290(22):13875-13887). This promotes inflammation and hyperalgesia via the release of CGRP (calcitonin gene-related peptide) and SP (substance P) from spinal cord sensory neurons and the sensitization of Transient Receptors Potential Vanilloid (TRPV) TRPV1 and TRPV4 in sensory neurons (Vergnolle et al., Nat Med, 2001, 6(2):151-158; Steinhoff et al., Nat Med, 2000, 6(2):151-158; Amadesi et al., J Neurosci, 2004, 24(18):4300-4312; Grant et al., J Physiol, 2007, 578(Pt 3), 715-733; Jimenez Vargas et al., Proc Natl Acad Sci USA, 2018, 115(31):E7438-E7447). This is supported by a large amount of in vivo data available in the literature demonstrating that inhibition of PAR-2 reduces inflammatory pain, neuropathic pain, cancer pain, and treatment-induced pain in animal models (Bao et al., Expert Opin Ther Targets, 2014;18(1):15-27; Chen et al., Neuroscience, 2011, 193, 440-451). Thus, PAR-2 is clearly involved in the generation and transmission of pain signals, neurogenic inflammation, and nociception.

[0012] The expression of PAR-2 and protease increases in the spinal cord after contusion-compression injury (Radulovic et al., Neurobiol Dis, 2015, 83, 75-89; Li et al., Physiol.Res., 2019, 68(2):305-316). Its activation can result in cAMP signaling in oligodendrocytes (Yoon et al., Glia, 2017, 65(12):2070-2086). In vitro and in vivo experiments in rodents have shown that inhibition of PAR-2 signaling during experimental spinal cord injury reduces inflammation, scar formation, and mechanical and thermal hyperalgesia, and improves remyelination of oligodendrocytes and motor function recovery (Radulovic et al., Neurobiol Dis, 2015, 83, 75-89; Li et al., Physiol.Res., 2019, 68(2):305-316; Yoon et al., Glia, 2017, 65(12):2070-2086; Li et al., Physiol.Res., 2019, 68(2):305-316; Wei et al., Physiol.Res., 2016, 65(1):145-53). Therefore, PAR-2 inhibitors may improve recovery from spinal cord injury.

[0013] Disorders of the immune system underlie many diseases. In all cases, the immune system attacks normal components of the organism as foreign substances. This becomes pathogenic and induces lesions in specific organs (e.g., type 1 diabetes in the pancreas or multiple sclerosis in the brain) or throughout the body (e.g., rheumatoid arthritis or systemic lupus erythematosus, SLE).

[0014] Cytokines are small proteins involved in cell signaling that direct the immune response. Dysregulation of their regulation underlies the etiology of autoinflammatory diseases. These conditions are characterized by immune activation, infiltration, and abnormal cytokine production. They include conditions such as rheumatic inflammatory diseases, skin inflammatory diseases, pulmonary inflammatory diseases, muscle inflammatory diseases, intestinal inflammatory diseases, brain inflammatory diseases, and autoimmune diseases.

[0015] Autoinflammatory diseases progress chronically, but some conditions can lead to acute immune disorders. In fact, a sudden, excessive, and uncontrolled release of pro-inflammatory cytokines, also known as cytokine storms, has been observed in graft-versus-host disease, multiple sclerosis, pancreatitis, multiple organ dysfunction syndrome, viral diseases, bacterial infections, hemophagocytic lymphohistiocytosis, and sepsis (Gerlach H, F1000Res, 2016, 5, 2909; Tisoncik JR et al., Microbiol Mol Biol Rev, 2012, 76(1):16 - 32). In these conditions, dysregulation of the immune response and subsequent excessive inflammation can lead to multi-organ failure, which can be fatal.

[0016] PAR-2 affects the production of inflammatory cytokines and the function of various organs, and numerous studies have demonstrated that it is a promising therapeutic target for various autoinflammatory diseases.

[0017] The expression of protease and PAR-2 is significantly increased in organs directly involved in autoinflammatory diseases such as the coronary arteries of patients with atherosclerosis (Jones et al., Arterioscler Thromb Vasc Biol, 2018, 38(6):1271-1282), the skin of patients with atopic dermatitis and psoriasis (Nattkemper et al., Journal of Investigative Dermatology, 2018, 138:1311-1317), the joints of patients with rheumatoid arthritis and osteoarthritis (Tindell et al., Rheum Int, 2012, 32(10):3077-86), the colon of patients with inflammatory bowel disease (Christerson et al., J Crohns Colitis, 2009, 3(1):15-24; Kim et al., Inflamm Bowel Dis., 2003, 9(4):224-9), the lungs of patients with idiopathic pulmonary fibrosis (Bardou et al., Am J Respir Crit Care Med, 2016, 193(8):847-60), the liver of patients with non-alcoholic steatohepatitis (Rana et al., Mol Metab, 2019, 29:99-113), and the active demyelinated areas in the brains of patients with multiple sclerosis (Noorbakhsh et al., J Exp Med, 2006, 203(2):425-35).

[0018] Therefore, PAR-2 activation leads to calcium signaling in multiple cells such as osteoblasts, fibroblasts, monocytes, and keratinocytes (Abraham et al., Bone, 2000, 26(1):7-14; Lin et al., J. Cell. Mol. Med., 2015, 19(6):1346-56; Johansson et al., J leukoc Biol, 2005, 78(4):967-75; Joo et al., Bio Mol Ther, 2016, 24(5):529-535). This signaling is associated with cell maturation and / or migration, activation, and secretion of inflammatory cytokines such as IL-8, IL-6, TNFα, and IL-1β in various cell types such as vascular smooth muscle cells, synoviocytes, monocytes, keratinocytes, astrocytes, chondrocytes, adipocytes, and fibroblasts (Demetz et al., Atherosclerosis, 2010, 212:466-471; Kelso et al., Arthritis Rheum, 2007, 56(3):765-71; Johansson et al., J Leukoc Biol, 2005, 78(4):967-75; Steven et al., Innate Immun, 2013, 19(6):663-72; Kim et al., Bio Mol Ther, 2012, 20(5):463-9; Radulovic et al., Neurobiol Dis, 2015, 83, 75-89; Lin et al., J. Cell. Mol. Med., 2015, 19(6):1346-56; Bagher et al., Cell Communi and Signal, 2018, 16(1), 59; Huang et al., Aging, 2019, 11(24):12532-12545; Bandeanlou et al., Nat. Med., 2011, 17:1490-1497).PAR-2 signaling also affects tissue remodeling through its role in the survival of key cells such as neurons and chondrocytes in central nervous system disorders and rheumatic inflammatory diseases (Afkhami-Goli et al., J Immunol, 2007, 179(8):5493-503; Huang et al., Aging, 2019, 11(24):12532-12545), as well as the secretion of growth factors (e.g., CTGF) and extracellular components (e.g., collagen) (Lin et al., Mol. Med., 2015, 21(1):576-83; Chung et al., J Biol Chem, 2013, 288(52):37319-31). It is important to note that other signaling pathways such as cyclic AMP in alveolar macrophages and Gi in hepatocytes are thought to be important for regulating cytokine secretion and steatosis, respectively (Rayees et al., Cell Rep, 2019, 27(3):793-805.e4; Rana et al., Mol Metab, 2019, 29, 99-113).

[0019] In vivo, in mouse models, inhibition of PAR-2 signaling by pharmacological or genetic modification has been clearly shown to significantly reduce the symptoms of atherosclerosis, idiopathic pulmonary fibrosis, atopic dermatitis, multiple sclerosis, arthritis, non-alcoholic steatohepatitis, and inflammatory bowel disease (Jones et al., Arterioscler Thromb Vasc Biol, 2018, 38(6):1271-1282; Borensztajn et al., Am J Pathol, 2010, 177(6):2753-64; Moniaga et al., Am J Pathol, 2013, 182:841e851; Noorbakhsh et al., J Exp Med, 2006, 203(2):425-35, Ferrell et al., J Clin Invest, 2003, 111(1):35-41; Rana et al., Mol Metab, 2019, 29:99-113; Hyun et al., Gut, 2008, 57(9):1222-9). Therefore, PAR-2 plays a major role in the molecular and cellular mechanisms underlying the etiology of autoinflammatory diseases.

[0020] PAR-2-dependent inflammation also impairs cell metabolism and promotes insulin resistance, which can in turn lead to the etiology of diabetes, obesity, and metabolic syndrome. Indeed, PAR-2 expression in adipose tissue correlates with the increase in BMI of volunteer people, and inhibition of PAR-2 signaling attenuates the symptoms of metabolic disorders in mice (Lim et al., FASEB Journal, 2013, 27(12):4757-4767; Badeanlou et al., Nat. Med., 2011, 17(11):1490-1497).

[0021] Many airborne allergens derived from indoor dust mites and cockroach allergens contain protease activity. This protease activity can activate PAR-2 expressed on human airway epithelial cells, endothelial cells, and immune cells and induce calcium signaling. This ultimately results in the release of inflammatory cytokines and angiogenesis responses that underlie the etiology of cockroach allergy and allergic asthma (Do et al., Allergy, 2016, 71(4):463-74; Asosingh et al., J Clin Invest, 2018, 128(7):3116-3128). In vivo, in mice, functional blockade of PAR-2 in the airways during allergen challenge improves allergen-induced inflammation and airway hyperresponsiveness (Asaduzzaman et al., Clin Exp Allergy, 2015, 45(12):1844-55).

[0022] The expression of PAR-2 and protease is also significantly increased in many cancer types such as cervical squamous cell carcinoma, endocervical adenocarcinoma, colorectal adenocarcinoma, esophageal cancer, glioblastoma multiforme, acute myeloid leukemia, lung adenocarcinoma, lung squamous cell carcinoma, ovarian serous cystadenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, rectal adenocarcinoma, gastric adenocarcinoma, testicular germ cell tumor, endometrial carcinoma of the uterine corpus, carcinosarcoma of the uterus, hepatocellular carcinoma, and breast cancer, which may be associated with poor prognosis (Kaufmann et al., Carcinogenesis, 2009, 30(9):1487-96; Su et al., Oncogene, 2009, 28(34):3047-57; Arakaki et al., Int. J. Mol. Sci. 2018, 19, 1886). Activation of this receptor in cancer cells can lead to multiple signaling cascades such as calcium, β-arrestin, and Gi signaling (Kaufmann et al., J Cancer Res Clin Oncol, 2011, 137(6):965-73; Wu et al., Mol Med Rep, 2014, 10(6):3021-6; Ge et al., J Biol Chem, 2004, 279(53):55419-24). This ultimately controls cancer cell migration, proliferation, survival, and the expression of inflammatory cytokines (Jiang et al., J Pharmacol Exp Ther, 2018, 364(2):246-257; Darmoul et al., British J Cancer, 2001, 85(5):772-9; Quan et al., Oncol Res., 2019, 27(7):779-788).The expression of PAR-2 on other cells in the tumor microenvironment, such as immune cells, fibroblasts, endothelial cells, and DRG neurons, can also control the immune response against cancer cells, fibrosis, as well as angiogenesis and cancer-induced pain (Mubbach et al., Mol cancer, 2016, 15(1):54; Uusitalo-Jarvinen et al., Arteriocler Thromb Vasc Biol, 2007, 27(6):1456-62; D’Andrea et al., Am J Pathol, 2001, 158(6):2031-41; Graf et al., Sci Immunol, 2019, 4(39):eaaw8405; Qian et al., Oncol Lett, 2018, 16(2):1513-20; Tu et al., J Neurosci, 2021, 41(1):193-210). In vivo, in mouse models of different cancers such as breast cancer, liver cancer, and colon cancer, inhibition of PAR-2 has been shown to be an efficient way to reduce tumor growth and increase survival (Versteeg et al., Cancer Res, 2008, 68(17):7219-27; Sun et al., World J Gastroenterol, 2018, 24(10):1120-1133; Quan et al., Oncol Res., 2019, 27(7):779-788). Importantly, in multiple syngeneic mouse models, inhibition of PAR2 or one of its ligands led to a decrease in the infiltration of immunosuppressive tumor-associated macrophages and regulatory T cells, while increasing cytotoxic T cells in the tumor and antigen-presenting cells in the draining regional lymph nodes, which triggered an anti-tumor immune response and increased the efficacy of currently used immune checkpoint inhibitors in the clinic (Graf et al., Sci Immunol, 2019, 4(39):eaaw8405). Therefore, PAR-2 constitutes a promising therapeutic target in oncology and immuno-oncology.

[0023] Considering the role of PAR-2 in multiple pathophysiological states, inhibitors of this receptor may have therapeutic applications in a variety of human diseases. This has attracted great interest from the pharmaceutical industry for the development of such compounds. Various PAR-2 inhibitors and their therapeutic uses have been proposed, for example, in Yau et al., Expert Opin Ther Pat, 2016, 26(4):471-83; Jiang et al., J Pharmacol Exp Ther, 2018, 364(2):246-57; WO2004 / 002418; WO2005 / 030773; WO2012 / 012843; WO2012 / 026765; WO2012 / 026766; WO2012 / 101453; WO2015 / 048245; WO2016 / 154075; WO2017 / 194716; WO2017 / 197463; WO2018 / 043461 (EP3508487); WO2018 / 057588; WO2019 / 163956 (EP3760631); WO2019 / 199800; JP2020 / 007262; and WO2021 / 106864. However, despite the efforts made in the past decade, PAR-2 inhibitors have not yet reached the market (Yau et al., Expert Opin Ther Pat., 2016, 26(4):471-83). Therefore, there remains an unmet need for novel and / or improved PAR-2 inhibitors with high potency, selectivity, and bioavailability.

Summary of the Invention

Means for Solving the Problems

[0024] The present invention addresses this need and solves the problem of providing novel and very potent PAR-2 inhibitors. In particular, surprisingly, the compounds of formula (I) provided herein are potent inhibitors of PAR-2 signaling, whereby these compounds are advantageous for use in the treatment or prevention of therapies such as, in particular, pain, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, central nervous system disorders, spinal cord injuries, metabolic disorders, gastrointestinal disorders, cardiovascular disorders, fibrotic disorders, respiratory disorders, skin disorders, allergic disorders, or cancer.

[0025] Accordingly, the present invention provides a compound of formula (I) below

[0026]

Chemical formula

[0027] or a pharmaceutically acceptable salt or solvate thereof. In formula (I), ring B is a non-aromatic C 4~8 carbocyclic ring or non-aromatic 4- to 8-membered heterocyclic ring fused to ring D, and the carbocyclic ring or the heterocyclic ring is (i) substituted with group R 1 and (ii) substituted with groups R 2A and R 2B bonded to the same ring carbon atom of the carbocyclic ring or the heterocyclic ring, and (iii) may be substituted with one or more groups R Y .

[0028] Ring D is a 5- or 6-membered aromatic heterocyclic ring fused to ring B, the aromatic heterocyclic ring contains at least one nitrogen ring atom, the aromatic heterocyclic ring is substituted with the group -L-A, and the aromatic heterocyclic ring may be substituted with one or more groups R X .

[0029] R 1 is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~5-(alkylene)-carbocyclyl, and -(C 0~5 is selected from -alkylene)-heterocyclyl, wherein said alkyl, said alkenyl, said alkynyl, said -(C 0~5 The alkylene group in -alkylene)-carbocyclyl, and said -(C 0~5 The alkylene group in -alkylene)-heterocyclyl may each be substituted with one or more groups R 12 , and one or more of the -CH2- units contained in said alkyl, said alkenyl, said alkynyl, said -(C 0~5 The alkylene group in -alkylene)-carbocyclyl, or said -(C 0~5 The alkylene group in -alkylene)-heterocyclyl may each be replaced by a group independently selected from -C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 ), and each R L1 is independently hydrogen or C 1~5 alkyl, and two groups R L1 bonded to the same carbon atom may also be joined to each other to form a cycloalkyl or heterocycloalkyl together with the carbon atom to which they are bonded, and said -(C 0~5 The carbocyclyl group in -alkylene)-carbocyclyl and said -(C 0~5 The heterocyclyl group in -alkylene)-heterocyclyl may each be substituted with one or more groups R 11 .

[0030] Each R 11 is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~3 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-O(C 1~5 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkylene)-O(C1~5 alkyl), -(C 0~3 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-S(C 1~5 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-NH2, -(C 0~3 alkylene)-NH(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-OH, -(C 0~3 alkylene)-N(C 1~5 alkyl)-OH, -(C 0~3 alkylene)-NH-O(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-O(C 1~5 alkyl), -(C 0~3 alkylene)-halogen, -(C 0~3 alkylene)-(C 1~5 haloalkyl), -(C 0~3 alkylene)-O-(C 1~5 haloalkyl), -(C 0~3 alkylene)-CN, -(C 0~3 alkylene)-CHO, -(C 0~3 alkylene)-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-COOH, -(C 0~3 alkylene)-CO-O-(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-CO-NH2, -(C 0~3 alkylene)-CO-NH(C 1~5 alkyl), -(C 0~3 alkylene)-CO-N(C1~5 (alkyl)(C 1~5 (alkyl), -(C 0~3 (alkylene)-NH-CO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-NH-COO(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -(C 0~3 (alkylene)-O-CO-NH(C 1~5 (alkyl), -(C 0~3 (alkylene)-O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-NH2, -(C 0~3 (alkylene)-SO2-NH(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -(C 0~3 (alkylene)-NH-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-carbocyclic, -(C 0~3 (alkylene)-heterocyclic, and -L Z -R Z independently selected from, said -(C 0~3 the carbocyclic group in (alkylene)-carbocyclic and said -(C 0~3 the heterocyclic group in (alkylene)-heterocyclic may each be substituted with one or more groups R Cyc and may be.

[0031] Each R 12 is -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -NH-OH, -N(C 1~5 alkyl)-OH, -NH-O(C 1~5 alkyl), -N(C 1~5 alkyl)-O(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO-(C 1~5 alkyl), -COOH, -CO-O-(C 1~5 alkyl), -O-CO-(C 1~5 alkyl), -CO-NH2, -CO-NH(C 1~5 alkyl), -CO-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-CO-(C 1~5 alkyl), -N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -NH-COO(C 1~5 alkyl), -N(C 1~5 alkyl)-COO(C 1~5 alkyl), -O-CO-NH(C 1~5 alkyl), -O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -SO2-NH2, -SO2-NH(C 1~5 alkyl), -SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-SO2-(C 1~5 alkyl), -N(C1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), -SO2-(C 1~5 (alkyl), carbocyclic, heterocyclic, and -L Z -R Z is independently selected from, said carbocyclic and said heterocyclic are each optionally substituted with one or more groups R Cyc .

[0032] R 2A and R 2B are joined to each other and together with the carbon atoms to which they are attached form cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, said cycloalkyl, said cycloalkenyl, said heterocycloalkyl or said heterocycloalkenyl is optionally substituted with one or more groups R 21 or, or R 2A and R 2B are each independently selected from C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~5 alkylene)-carbocyclic, and -(C 0~5 alkylene)-heterocyclic, said alkyl, said alkenyl, said alkynyl, the alkylene group in said -(C 0~5 alkylene)-carbocyclic, and the alkylene group in said -(C 0~5 alkylene)-heterocyclic are each optionally substituted with one or more groups R 22 and one or more -CH2- units contained in said alkyl, said alkenyl, said alkynyl, the alkylene group in said -(C 0~5 alkylene)-carbocyclic, or the alkylene group in said -(C 0~5 alkylene)-heterocyclic are each -O-, -NH-, -N(C 1~5may be replaced by a group independently selected from alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, said -(C 0~5 The carbocyclic group in the (alkylene)-carbocyclic and said -(C 0~5 The heterocyclic group in the (alkylene)-heterocyclic may each be substituted with one or more groups R Cyc and R 2A and the group R Y may also be joined to each other and together with the ring atoms to which they are attached form a carbocyclic or heterocyclic ring, and said carbocyclic or said heterocyclic may be substituted with one or more groups R Cyc .

[0033] Each R 21 is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~3 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-O(C 1~5 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-S(C 1~5 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-NH2, -(C 0~3 alkylene)-NH(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3-(Alkylene)-NH-OH, -(C 0~3 -(Alkylene)-N(C 1~5 -(Alkyl)-OH, -(C 0~3 -(Alkylene)-NH-O(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-N(C 1~5 -(Alkyl)-O(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-Halogen, -(C 0~3 -(Alkylene)-(C 1~5 -(Haloalkyl), -(C 0~3 -(Alkylene)-O-(C 1~5 -(Haloalkyl), -(C 0~3 -(Alkylene)-CN, -(C 0~3 -(Alkylene)-CHO, -(C 0~3 -(Alkylene)-CO-(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-COOH, -(C 0~3 -(Alkylene)-CO-O-(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-O-CO-(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-CO-NH2, -(C 0~3 -(Alkylene)-CO-NH(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-CO-N(C 1~5 -(Alkyl)(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-NH-CO-(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-N(C 1~5 -(Alkyl)-CO-(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-NH-COO(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-N(C 1~5 -(Alkyl)-COO(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-O-CO-NH(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-O-CO-N(C1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-NH2, -(C 0~3 alkylene)-SO2-NH(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-SO-(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-carbocyclic, -(C 0~3 alkylene)-heterocyclic, and -L Z -R Z is independently selected from, said -(C 0~3 The carbocyclic group in alkylene)-carbocyclic and the heterocyclic group in said -(C 0~3 The heterocyclic group in alkylene)-heterocyclic may each be substituted with one or more groups R Cyc .

[0034] Each R 22 is -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -NH-OH, -N(C 1~5(alkyl)-OH, -NH-O(C 1~5 (alkyl), -N(C 1~5 (alkyl)-O(C 1~5 (alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO-(C 1~5 (alkyl), -COOH, -CO-O-(C 1~5 (alkyl), -O-CO-(C 1~5 (alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-CO-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -NH-COO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), -SO2-(C 1~5 (alkyl), carbocyclic, heterocyclic, and -L Z -R Z independently selected from, wherein said carbocyclic and said heterocyclic are each optionally substituted with one or more groups R Cyc .

[0035] Each R X is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~3-(Alkylene)-OH, -(C 0~3 -(Alkylene)-O(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-O(C 1~5 -(Alkylene)-OH, -(C 0~3 -(Alkylene)-O(C 1~5 -(Alkylene)-O(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-SH, -(C 0~3 -(Alkylene)-S(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-S(C 1~5 -(Alkylene)-SH, -(C 0~3 -(Alkylene)-S(C 1~5 -(Alkylene)-S(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-NH2, -(C 0~3 -(Alkylene)-NH(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-N(C 1~5 -(Alkyl)(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-NH-OH, -(C 0~3 -(Alkylene)-N(C 1~5 -(Alkyl)-OH, -(C 0~3 -(Alkylene)-NH-O(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-N(C 1~5 -(Alkyl)-O(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-halogen, -(C 0~3 -(Alkylene)-(C 1~5 -(Haloalkyl), -(C 0~3 -(Alkylene)-O-(C 1~5 -(Haloalkyl), -(C 0~3 -(Alkylene)-CN, -(C 0~3 -(Alkylene)-CHO, -(C 0~3 -(Alkylene)-CO-(C 1~5 -(Alkyl), -(C 0~3 -(Alkylene)-COOH, -(C 0~3 -(Alkylene)-CO-O-(C 1~5 -(Alkyl), -(C0~3 (alkylene)-O-CO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-CO-NH2, -(C 0~3 (alkylene)-CO-NH(C 1~5 (alkyl), -(C 0~3 (alkylene)-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -(C 0~3 (alkylene)-NH-CO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-NH-COO(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -(C 0~3 (alkylene)-O-CO-NH(C 1~5 (alkyl), -(C 0~3 (alkylene)-O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-NH2, -(C 0~3 (alkylene)-SO2-NH(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -(C 0~3 (alkylene)-NH-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-carbocyclic, -(C 0~3 (alkylene)-heterocyclic, and -L Z -RZ selected independently from, said -(C 0~3 the carbocyclic group in alkylene)-carbocyclic and said -(C 0~3 the heterocyclic group in alkylene)-heterocyclic may each be substituted with one or more groups R Cyc .

[0036] Each R Y is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~3 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-O(C 1~5 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-S(C 1~5 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-NH2, -(C 0~3 alkylene)-NH(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-OH, -(C 0~3 alkylene)-N(C 1~5 alkyl)-OH, -(C 0~3 alkylene)-NH-O(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-O(C 1~5 alkyl), -(C 0~3 alkylene)-halogen, -(C0~3 (alkylene)-(C 1~5 haloalkyl), -(C 0~3 alkylene)-O-(C 1~5 haloalkyl), -(C 0~3 alkylene)-CN, -(C 0~3 alkylene)-CHO, -(C 0~3 alkylene)-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-COOH, -(C 0~3 alkylene)-CO-O-(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-CO-NH2, -(C 0~3 alkylene)-CO-NH(C 1~5 alkyl), -(C 0~3 alkylene)-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-NH-COO(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-COO(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-NH(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-NH2, -(C 0~3 alkylene)-SO2-NH(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3(alkylene)-NH-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-carbocyclic, -(C 0~3 (alkylene)-heterocyclic, and -L Z -R Z is independently selected from, said -(C 0~3 The carbocyclic group in (alkylene)-carbocyclic and the heterocyclic group in said -(C 0~3 (alkylene)-heterocyclic may each be substituted with one or more groups R Cyc and, Any two groups R bonded to the same ring carbon atom Y may also (i) join together to form, together with the carbon atom to which they are attached, cycloalkyl or heterocycloalkyl, said cycloalkyl or said heterocycloalkyl may be substituted with one or more groups R Cyc or (ii) form a group =O with each other.

[0037] L is selected from -CO-, -SO- and -SO2-. Group A is -N(-R N )-R N or heterocyclic, said heterocyclic is bonded to group L via a ring nitrogen atom, said heterocyclic may be substituted with one or more groups R A and.

[0038] Each R N is hydrogen, C 1~8 alkyl, C 2~8 alkenyl, C 2~8 alkynyl, -(C 0~8 (alkylene)-OH, -(C 0~8(Alkylene)-O(C 1~5 Alkyl), -(C 0~8 (Alkylene)-SH, -(C 0~8 (Alkylene)-S(C 1~5 Alkyl), -(C 1~8 (Alkylene)-NH2, -(C 1~8 (Alkylene)-NH(C 1~5 Alkyl), -(C 1~8 (Alkylene)-N(C 1~5 Alkyl)(C 1~5 Alkyl), -(C 1~8 (Alkylene)-Halogen, -(C 1~8 (Alkylene)-C 1~5 Haloalkyl, -(C 0~8 (Alkylene)-O-(C 1~8 Haloalkyl), -(C 0~8 (Alkylene)-CN, -(C 0~8 (Alkylene)-CHO, -(C 0~8 (Alkylene)-CO-(C 1~5 Alkyl), -(C 0~8 (Alkylene)-COOH, -(C 0~8 (Alkylene)-CO-O-(C 1~5 Alkyl), -(C 0~8 (Alkylene)-O-CO-(C 1~5 Alkyl), -(C 0~8 (Alkylene)-CO-NH2, -(C 0~8 (Alkylene)-CO-NH(C 1~5 Alkyl), -(C 0~8 (Alkylene)-CO-N(C 1~5 Alkyl)(C 1~5 Alkyl), -(C 1~8 (Alkylene)-NH-CO-(C 1~5 Alkyl), -(C 1~8 (Alkylene)-N(C 1~5 Alkyl)-CO-(C 1~5 Alkyl), -(C 1~8 (Alkylene)-NH-COO(C 1~5 Alkyl), -(C 1~8 (Alkylene)-N(C 1~5 Alkyl)-COO(C 1~5 Alkyl), -(C 0~8 (Alkylene)-O-CO-NH(C1~5 alkyl), -(C 0~8 alkylene)-O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~8 alkylene)-SO2-NH2, -(C 0~8 alkylene)-SO2-NH(C 1~5 alkyl), -(C 0~8 alkylene)-SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 1~8 alkylene)-NH-SO2-(C 1~5 alkyl), -(C 1~8 alkylene)-N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -(C 0~8 alkylene)-SO-(C 1~5 alkyl), -(C 0~8 alkylene)-SO2-(C 1~5 alkyl), -(C 0~8 alkylene)-carbocyclic, and -(C 0~8 alkylene)-heterocyclic, independently selected from, said C 1~8 alkyl, said C 2~8 alkenyl, said C 2~8 alkynyl, as well as the aforementioned C 0~8 alkylene and C 1~8 alkylene group, one or more of the -CH2- units contained in any of which may each be replaced by a group independently selected from -O-, -NH-, -N(C 1~5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, said -(C 0~8 alkylene)-carbocyclic group in the carbocyclic group and said -(C 0~8 alkylene)-heterocyclic group in the heterocyclic group may each be substituted with one or more groups R Cyc and at least one group R N is not hydrogen.

[0039] Each R A is C 1~5 alkyl, C2~5 Alkenyl, C 2~5 Alkynyl, -(C 0~3 Alkylene)-OH, -(C 0~3 Alkylene)-O(C 1~5 Alkyl), -(C 0~3 Alkylene)-O(C 1~5 Alkylene)-OH, -(C 0~3 Alkylene)-O(C 1~5 Alkylene)-O(C 1~5 Alkyl), -(C 0~3 Alkylene)-SH, -(C 0~3 Alkylene)-S(C 1~5 Alkyl), -(C 0~3 Alkylene)-S(C 1~5 Alkylene)-SH, -(C 0~3 Alkylene)-S(C 1~5 Alkylene)-S(C 1~5 Alkyl), -(C 0~3 Alkylene)-NH2, -(C 0~3 Alkylene)-NH(C 1~5 Alkyl), -(C 0~3 Alkylene)-N(C 1~5 Alkyl)(C 1~5 Alkyl), -(C 0~3 Alkylene)-NH-OH, -(C 0~3 Alkylene)-N(C 1~5 Alkyl)-OH, -(C 0~3 Alkylene)-NH-O(C 1~5 Alkyl), -(C 0~3 Alkylene)-N(C 1~5 Alkyl)-O(C 1~5 Alkyl), -(C 0~3 Alkylene)-halogen, -(C 0~3 Alkylene)-(C 1~5 Haloalkyl), -(C 0~3 Alkylene)-O-(C 1~5 Haloalkyl), -(C 0~3 Alkylene)-CN, -(C 0~3 Alkylene)-CHO, -(C 0~3 Alkylene)-CO-(C 1~5 Alkyl), -(C 0~3 Alkylene)-COOH, -(C0~3 (alkylene)-CO-O-(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-CO-NH2, -(C 0~3 alkylene)-CO-NH(C 1~5 alkyl), -(C 0~3 alkylene)-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-NH-COO(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-COO(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-NH(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-NH2, -(C 0~3 alkylene)-SO2-NH(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-SO-(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-carbocyclic, -(C0~3 -(C alkylene)-heterocyclyl, and -L Z -R Z independently selected from, said -(C 0~3 The carbocyclic group in alkylene)-carbocyclyl and said -(C 0~3 The heterocyclic group in alkylene)-heterocyclyl may each be substituted with one or more groups R Cyc Further, any two groups R bonded to the same carbon atom of group A A may also be joined to each other and together with the carbon atom to which they are bonded form a cycloalkyl or heterocycloalkyl, and said cycloalkyl or said heterocycloalkyl may be substituted with one or more groups R Cyc .

[0040] Each R Cyc is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -NH-OH, -N(C 1~5 alkyl)-OH, -NH-O(C 1~5 alkyl), -N(C 1~5 alkyl)-O(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO(C 1~5 alkyl), -COOH, -COO(C 1~5 alkyl), -O-CO(C 1~5(alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C( 1~5 (alkyl)(C( 1~5 (alkyl), -NH-CO(C( 1~5 (alkyl), -N(C( 1~5 (alkyl)-CO(C( 1~5 (alkyl), -NH-COO(C( 1~5 (alkyl), -N(C( 1~5 (alkyl)-COO(C( 1~5 (alkyl), -O-CO-NH(C( 1~5 (alkyl), -O-CO-N(C( 1~5 (alkyl)(C( 1~5 (alkyl), -SO2-NH2, -SO2-NH(C( 1~5 (alkyl), -SO2-N(C( 1~5 (alkyl)(C( 1~5 (alkyl), -NH-SO2-(C( 1~5 (alkyl), -N(C( 1~5 (alkyl)-SO2-(C( 1~5 (alkyl), -SO2-(C( 1~5 (alkyl), -SO-(C( 1~5 (alkyl), -P(=O)(-OH)(-OH), -P(=O)(-OH)(-O-C( 1~5 (alkyl), -P(=O)(-O-C( 1~5 (alkyl)(-O-C( 1~5 (alkyl), -(C( 0~3 (alkylene)-cycloalkyl, -(C( 0~3 (alkylene)-heterocycloalkyl, and -L( Z -R( Z is independently selected from ( (

[0041] ( Each L( Z is a covalent bond, C( 1~7 alkylene, C( 2~7 alkenylene, and C( 2~7 alkynylene, independently selected therefrom, and said alkylene, said alkenylene and said alkynylene are each halogen, C( 1~5 haloalkyl, -O-(C( 1~5 haloalkyl), -CN, -OH, -O(C( 1~5 alkyl), -SH, -S(C1~5 (alkyl), -NH2, -NH(C 1~5 (alkyl), and -N(C 1~5 (alkyl)(C 1~5 It may be substituted with one or more groups independently selected from (alkyl), and further, one or more -CH2- units contained in the alkylene, alkenylene or alkynylene may each be replaced by a group independently selected from -O-, -NH-, -N(C 1~5 (alkyl)-, -CO-, -S-, -SO-, and -SO2-.

[0042] Each R Z is -OH, -O(C 1~5 (alkyl), -O(C 1~5 (alkylene)-OH, -O(C 1~5 (alkylene)-O(C 1~5 (alkyl), -SH, -S(C 1~5 (alkyl), -S(C 1~5 (alkylene)-SH, -S(C 1~5 (alkylene)-S(C 1~5 (alkyl), -NH2, -NH(C 1~5 (alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-OH, -N(C 1~5 (alkyl)-OH, -NH-O(C 1~5 (alkyl), -N(C 1~5 (alkyl)-O(C 1~5 (alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO(C 1~5 (alkyl), -COOH, -COO(C 1~5 (alkyl), -O-CO(C 1~5 (alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-CO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO(C 1~5 (alkyl), -NH-COO(C1~5 alkyl), -N(C 1~5 alkyl)-COO(C 1~5 alkyl), -O-CO-NH(C 1~5 alkyl), -O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -SO2-NH2, -SO2-NH(C 1~5 alkyl), -SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-SO2-(C 1~5 alkyl), -N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -SO2-(C 1~5 alkyl), -SO-(C 1~5 alkyl), aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, independently selected, wherein said aryl, said heteroaryl, said cycloalkyl, and said heterocycloalkyl are each, C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -CHO, -CO-(C 1~5 alkyl), -COOH, -CO-O-(C 1~5 alkyl), -O-CO-(C 1~5 alkyl), -CO-NH2, -CO-NH(C 1~5 alkyl), -CO-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-CO-(C 1~5 alkyl), -N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -NH-COO(C 1~5 alkyl), -N(C 1~5 alkyl)-COO(C 1~5(alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), -SO2-(C 1~5 (alkyl), and may be substituted with one or more groups independently selected from carbocyclic and heterocyclic, wherein said carbocyclic and said heterocyclic are each C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), -CHO, -CO-(C 1~5 (alkyl), -COOH, -CO-O-(C 1~5 (alkyl), -O-CO-(C 1~5 (alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-CO-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -NH-COO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C1~5 alkyl), -SO2-NH2, -SO2-NH(C 1~5 alkyl), -SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-SO2-(C 1~5 alkyl), -N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -SO-(C 1~5 alkyl), and -SO2-(C 1~5 alkyl) and may be substituted with one or more groups independently selected from

[0043] Preferably, the following conditions apply to the compound of formula (I): - Ring B is a pyrrolidinyl ring, ring D is a pyridinyl ring, R 2A and R 2B are joined to each other and together with the carbon atom to which they are attached form a cyclopropyl, L is -CO-, and when group A is morpholin-4-yl, R 1 is not 5-R 11 -pyrimidin-2-yl or acetyl, - Rings B and D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl ring, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-c]pyridinyl ring or 6-oxo-6,7-dihydro-5H-pyrrolo[2,3-c]pyridazinyl ring, R 2A and R 2B are each methyl, R 1 is phenyl which may be substituted with one or more groups R 11 and when L is -CO- and group A is -NH-R N R N is not a heterocycloalkyl containing one oxidized sulfur ring atom and all other ring atoms being carbon atoms and substituted with a methyl group, - Rings B and D together form a 3-R X -4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring, R X is -OH, R2A and R 2B one of which is methyl and R 2A and R 2B the other one of which is -CON(-CH3)2 and R 1 is methyl, L is -CO-, and the group A is -NH-R N when it is, R N is not 4-fluorobenzyl, - Rings B and D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine ring, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine ring or 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine, L is -CO-, and the group A is -NH-R N when it is, R 1 is -CH2-phenyl or -CH2-pyridinyl, and the phenyl in the -CH2-phenyl and the pyridinyl in the -CH2-pyridinyl are each optionally substituted with one or more groups R 11 when it is, R 2A and R 2B are not methyl.

[0044] 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. Accordingly, the present invention relates to a pharmaceutical composition for use as a medicament, comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the aforementioned entities, and a pharmaceutically acceptable excipient.

[0045] The present invention further relates to a pharmaceutical composition for use in the treatment or prevention of a PAR-2 mediated disease or disorder, comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the foregoing constructs, and a pharmaceutically acceptable excipient. Accordingly, the present invention provides, in particular, a pharmaceutical composition comprising, as an active ingredient, a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, together with a pharmaceutically acceptable excipient, for use in the treatment or prevention of a PAR-2 mediated disease or disorder.

[0046] 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 medicament for the treatment or prevention of a PAR-2 mediated disease or disorder.

[0047] Similarly, the present invention relates to a method of treating or preventing a PAR-2 mediated disease or disorder, comprising administering to a subject (preferably a human) in need thereof a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the foregoing constructs, in combination with a pharmaceutically acceptable excipient. It will be understood that a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof (or the pharmaceutical composition) is administered according to this method.

[0048] As described above, the diseases or disorders treated or prevented by the compounds of formula (I) according to the invention, or their pharmaceutically acceptable salts or solvates (or corresponding pharmaceutical compositions), include any PAR-2 mediated disease or disorder. The diseases / disorders treated or prevented according to the invention are preferably pain (e.g., chronic pain), autoimmune disorders, autoinflammatory disorders, inflammatory disorders (e.g., rheumatic inflammatory disorders, skin inflammatory disorders, pulmonary inflammatory disorders, muscle inflammatory disorders, intestinal inflammatory disorders, or cerebral inflammatory disorders), central nervous system disorders, spinal cord injuries, metabolic disorders, gastrointestinal disorders, cardiovascular disorders, fibrotic disorders, respiratory disorders, skin disorders, allergic disorders, or cancer. More preferably, the diseases / disorders treated or prevented according to the invention are neuropathic pain, inflammatory pain, cancer pain, postoperative incision pain, fracture pain, osteoporotic fracture pain, gouty joint pain, chronic pain, spinal cord injury, atopic dermatitis, contact dermatitis, dry skin dermatitis, seborrheic dermatitis, arthritis, rheumatoid arthritis, osteoarthritis, psoriasis, psoriatic arthritis, multiple sclerosis, non-alcoholic steatohepatitis (NASH), obesity (e.g., diet-induced obesity), diabetes (e.g., type 1 diabetes or type 2 diabetes), adipose inflammation, pancreatitis, metabolic syndrome, PAR-2 related metabolic dysfunction, periodontitis, gingivitis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, peptic ulcer disease (e.g., gastric ulcer or duodenal ulcer), infectious enteritis, irritable bowel syndrome, atherosclerosis, asthma, interstitial lung disease, pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis), rheumatoid arthritis related interstitial lung disease, liver fibrosis, cystic fibrosis, renal fibrosis, peritoneal fibrosis, pancreatic fibrosis, intestinal fibrosis, cardiac fibrosis, skin fibrosis, systemic lupus erythematosus (SLE), scleroderma, skin eczema, acne, rosacea, post-inflammatory hyperpigmentation, lichen planus, pruritus, polymyositis, vasculitis, Wegener's granulomatosis (or granulomatosis with polyangiitis), Netherton syndrome, dermatomyositis, uveitis, cirrhosis, Alzheimer's disease, Parkinson's disease, dust mite allergy (e.g., house dust miteallergy), cockroach allergy, allergic asthma, colorectal cancer, colon cancer (e.g., colon adenocarcinoma), gastric cancer (e.g., gastric adenocarcinoma), rectal cancer (e.g., rectal adenocarcinoma), liver cancer (e.g., hepatocellular carcinoma), breast cancer, pancreatic cancer (e.g., pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma), cervical cancer (e.g., cervical squamous cell carcinoma or endocervical adenocarcinoma), prostate cancer (e.g., prostatic adenocarcinoma), ovarian cancer (e.g., ovarian serous cystadenocarcinoma), endometrial cancer (e.g., endometrial carcinoma of the uterine body), uterine sarcoma (e.g., carcinosarcoma of the uterus), germ cell cancer (e.g., testicular germ cell cancer), esophageal cancer, leukemia (e.g., acute myeloid leukemia), lung cancer (e.g., lung adenocarcinoma or lung squamous cell carcinoma), adrenal cancer (e.g., adrenocortical carcinoma), bile duct cancer (e.g., intrahepatic cholangiocarcinoma), bladder cancer (e.g., bladder urothelial carcinoma), head and neck cancer, kidney cancer (e.g., renal chromophobe cell, renal cell carcinoma of the kidney, clear cell renal cell carcinoma of the kidney, or papillary renal cell carcinoma of the kidney), lymphoma (e.g., diffuse large B-cell lymphoma of lymphoid neoplasm), mesothelioma, sarcoma, melanoma (e.g., skin cutaneous melanoma, or uveal melanoma), thyroid cancer, thymic cancer (e.g., thymoma), or glioblastoma.

[0049] Accordingly, the present invention particularly relates to neuropathic pain, inflammatory pain, cancer pain, postoperative incision pain, fracture pain, osteoporotic fracture pain, gouty arthritis pain, chronic pain, spinal cord injury, atopic dermatitis, contact dermatitis, xerotic dermatitis, seborrheic dermatitis, arthritis, rheumatoid arthritis, osteoarthritis, psoriasis, psoriatic arthritis, multiple sclerosis, non-alcoholic steatohepatitis (NASH), obesity (e.g., diet-induced obesity), diabetes, adipose tissue inflammation, pancreatitis, metabolic syndrome, PAR-2-related metabolic dysfunction, periodontitis, gingivitis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, peptic ulcer disease (e.g., gastric ulcer or duodenal ulcer), infectious enteritis, irritable bowel syndrome, atherosclerosis, asthma, interstitial lung disease, pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis), rheumatoid arthritis-related interstitial lung disease, liver fibrosis, cystic fibrosis, renal fibrosis, peritoneal fibrosis, pancreatic fibrosis, intestinal fibrosis, cardiac fibrosis, dermal fibrosis, systemic lupus erythematosus (SLE), scleroderma, skin eczema, acne, rosacea, post-inflammatory hyperpigmentation, lichen planus, pruritus, polymyositis, vasculitis, Wegener's granulomatosis (or granulomatosis with polyangiitis), Netherton syndrome, dermatomyositis, uveitis, cirrhosis, Alzheimer's disease, Parkinson's disease, scabies allergy (e.g., indoor scabies allergy), cockroach allergy, allergic asthma, or cancer (e.g., colorectal cancer, colon cancer (e.g., colon adenocarcinoma), gastric cancer (e.g., gastric adenocarcinoma), rectal cancer (e.g., rectal adenocarcinoma), liver cancer (e.g., hepatocellular carcinoma), breast cancer, pancreatic cancer (e.g., pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma), cervical cancer (e.g., cervical squamous cell carcinoma or endocervical adenocarcinoma), prostate cancer (e.g., prostate adenocarcinoma), ovarian cancer (e.g., ovarian serous cystadenocarcinoma), endometrial cancer (e.g., endometrial carcinoma of the uterine corpus), uterine sarcoma (e.g., carcinosarcoma of the uterus), germ cell cancer (e.g., testicular germ cell cancer), esophageal cancer, leukemia (e.g., acute myeloid leukemia), lung cancer (e.g., lung adenocarcinoma or lung squamous cell carcinoma), adrenal cancer (e.g., adrenocortical carcinoma), bile duct cancer (e.g., intrahepatic cholangiocarcinoma), bladder cancer (e.g., bladder urothelial carcinoma), head and neck cancer, kidney cancer (e.g., renal chromophobe cell, renal cell carcinoma of the kidney, clear cell renal cell carcinoma of the kidney, or papillary renal cell carcinoma of the kidney), lymphoma (e.g., diffuse large B-cell lymphoma of lymphoid neoplasm), mesothelioma, sarcoma, melanoma (e.g., cutaneous melanoma, or uveal melanoma), thyroid cancer,A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the foregoing constructs, and a pharmaceutically acceptable excipient, for use in the treatment or prevention of thymic cancer (e.g., thymoma), or glioblastoma.

[0050] The present invention also relates to a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof conjugated to a membrane anchor via a linker. The corresponding conjugate can be used in place of the compound of formula (I) for any of the uses or purposes described herein, for example, for use in the treatment or prevention of a PAR-2 mediated disease or disorder including any of the diseases / disorders described above herein. Such a conjugate is advantageous in that it anchors the conjugated compound of formula (I) to the cell membrane in proximity to PAR-2 and thus enables easier interaction with that PAR-2.

[0051] The membrane anchor may be any moiety capable of inserting / partitioning into a lipid membrane (preferably a cell membrane), particularly a hydrophobic or lipid moiety, whereby the conjugated compound of formula (I) is "fixed" to the corresponding lipid membrane. For example, the membrane anchor may be a C 12~20 alkanoyl group (e.g., hexadecanoyl group, -CO-(CH2) 14-CH3), cholesterol, cholestanol, sphingolipids, or glycosylphosphatidylinositol (GPI). The membrane anchor may also be, for example, as described in WO2017 / 197463, which is incorporated herein by reference, particularly the portions of defined formulas (II), (III), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV) or (XV) on pages 10 to 15 of WO2017 / 197463. The membrane anchor may further be, for example, raftophile A or A' as described in WO2005 / 097199, which is incorporated herein by reference, or any one of the portions of formulas 2, 200a to 200m, 3, 300a to 300g, 4a, 400aa to 400ap, 4b, 400ba, 5a, 500aa to 500ae, 5b, 500ba, 6, 600, 7, 700, 700a to 700c, 8a, 800a, 8b, 9, 900, 10, 1000, 11, 1100a, 1100b, 12, 1200a, 1200b, 13a, 1300aa to 1300ac, 13b, 1300b, 14a, 1400aa to 1400ae, 14b, 1400b, 14c, 15, 1500a, 16, 1600a, 18a, 1800a to 1800d, 18b, 19a, 1900a, 19b or 1900b.

[0052] The linker is covalently attached to the membrane anchor and the compound of formula (I) (or a pharmaceutically acceptable salt or solvate thereof). The linker is not particularly limited, but preferably has a length of about 1 nm to about 50 nm, and / or preferably provides a distance of at least 8 atoms between the compound of formula (I) and the membrane anchor. For example, the linker may (or may consist of) one or more polyethylene glycol (PEG) units, or may (or may consist of) a peptide (e.g., may be composed of 2 to 200 amino acid residues). The linker may also be, for example, a moiety of formula (IV), (XX), (XXI) or (XXII) described and defined in WO2017 / 197463, which is incorporated herein by reference, particularly on pages 15 to 18 of WO2017 / 197463. The linker may further be, for example, linker B or B' described and defined in WO2005 / 097199, which is incorporated herein by reference, or a moiety of any one of formulas 20, 2000, 2001, 21, 2100, 2101, 22, 23, 28 or 28a. It will be understood that the linker may be attached to the membrane anchor via any suitable chemical linkage, for example, via an amide linkage or an ester linkage. Similarly, the linker may be attached to the compound of formula (I) (or a pharmaceutically acceptable salt or solvate thereof) via any suitable chemical linkage, for example, via an amide linkage or an ester linkage. The linker may be attached at any position (or to any functional group) of the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, but the linker is attached to group A or substituent R on group A A is preferred.

[0053] Furthermore, the linker and the membrane anchor may together form any one of the moieties described as being attached to a PAR-2 inhibitor in WO2017 / 197463 (incorporated herein by reference), or a PAR-2 modulating compound in WO2017 / 173347 (incorporated herein by reference), or a pharmacophore in WO2005 / 097199 (incorporated herein by reference). Suitable protocols for the preparation of the corresponding linkers and membrane anchors are also described in these documents.

[0054] An example of the corresponding conjugate in which the compound of formula (I) is conjugated to the membrane anchor via a linker is described in Example 261. Accordingly, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof conjugated to a membrane anchor via a linker, wherein the membrane anchor is a C 12~20 alkanoyl group (e.g., hexadecanoyl group, -CO-(CH2) 14 -CH3). In particular, the present invention provides the compound N-(37-(4-(5'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutane-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazin-1-yl)-3-methyl-4,17,30,37-tetraoxo-7,10,13,20,23,26-hexaoxa-3,16,29-triazapentatriacontyl)-N-methylpalmitamide or a pharmaceutically acceptable salt or solvate thereof.

[0055] The present invention further relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as an inhibitor of protease-activated receptor 2 (PAR-2) in research, in particular as a research tool compound for inhibiting PAR-2. Accordingly, the present invention refers to the in vitro use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as a PAR-2 inhibitor, and in particular to the in vitro use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as a research tool compound that acts as a PAR-2 inhibitor. Similarly, the present invention relates to a method of inhibiting PAR-2, in particular an in vitro method, comprising the application of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. The present invention further relates to a method of inhibiting PAR-2, comprising the step of applying a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof to a test sample (e.g., a biological sample) or a test animal (i.e., a non-human test animal). The present invention also refers to a method of inhibiting PAR-2 in a sample (e.g., a biological sample), in particular an in vitro method, comprising the step of applying a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof to said sample. The present invention further provides a method of inhibiting PAR-2, comprising the step of contacting a test sample (e.g., a biological sample) or a test animal (i.e., a non-human test animal) with a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. The terms "sample", "test sample" and "biological sample" include, but are not limited to, cells, cell cultures or cell or intracellular extracts; biopsy material obtained from an animal (e.g., a human), or an extract thereof; or blood, serum, plasma, saliva, urine, feces, or any other bodily fluid, or an extract thereof.The term "in vitro" is used in this particular context to mean "outside the living human or animal body", which is understood to include experiments carried out using cells, cell or intracellular extracts, and / or biomolecules in an artificial environment such as an aqueous solution or a culture medium, which can be provided, for example, in flasks, test tubes, Petri dishes, microtiter plates, etc.

BEST MODE FOR CARRYING OUT THE INVENTION

[0056] The compounds of formula (I) and their pharmaceutically acceptable salts and solvates are described in more detail below.

[0057]

CHEM.

[0058] In formula (I), ring B is a non-aromatic C 4~8 carbocyclic ring or non-aromatic 4- to 8-membered heterocyclic ring fused to ring D, said carbocyclic ring or said heterocyclic ring being (i) substituted with group R 1 , (ii) substituted with groups R 2A and R 2B bonded to the same ring carbon atom of said carbocyclic ring or said heterocyclic ring, and (iii) optionally substituted with one or more (e.g., 1, 2 or 3) groups R Y .

[0059] Ring D is a 5- or 6-membered aromatic heterocyclic ring fused to ring B, said aromatic heterocyclic ring containing at least one nitrogen ring atom, said aromatic heterocyclic ring being substituted with group -L-A, and said aromatic heterocyclic ring being optionally substituted with one or more (e.g., 1, 2 or 3) groups R X .

[0060] Thus, as also depicted in formula (I), rings B and D are fused, i.e., they share two adjacent ring atoms (forming part of both ring B and ring D), thereby forming a fused bicyclic ring system. In this fused bicyclic ring system, only ring D is aromatic, while ring B is non-aromatic.

[0061] As described above, ring B is a non-aromatic C 4~8 carbocyclic ring or a non-aromatic 4- to 8-membered heterocyclic ring, and said carbocyclic ring or said heterocyclic ring may be substituted with one or more groups R Y Ring B is fused to ring D and is substituted with group R 1 and is substituted with group R 2A and R 2B (attached to the same ring carbon atom of ring B), but it is understood that these features, which are also depicted in formula (I), are not necessarily repeated in all cases where ring B is further described below in this specification.

[0062] Said non-aromatic C 4~8 carbocyclic ring is preferably a C 4~8 cycloalkyl ring or a C 4~8 cycloalkenyl ring, more preferably a C 5~7 cycloalkyl ring or a C 5~7 cycloalkenyl ring (e.g., a cyclohexenyl ring), even more preferably a cyclopentyl ring, a cyclohexyl ring, or a cycloheptyl ring.

[0063] Furthermore, the non-aromatic 4- to 8-membered heterocyclic ring is a 4- to 8-membered heterocycloalkyl ring or a 4- to 8-membered heterocycloalkenyl ring, more preferably a 5- to 7-membered heterocycloalkyl ring (i.e., a heterocycloalkyl ring having 5, 6, or 7 ring atoms) or a 5- to 7-membered heterocycloalkenyl ring (i.e., a heterocycloalkenyl ring having 5, 6, or 7 ring atoms; for example, 3,4-dihydro-2H-pyranyl ring or 3,6-dihydro-2H-pyranyl ring), even more preferably a 5- to 7-membered heterocycloalkyl ring (e.g., pyrrolidinyl ring, piperidinyl ring, 1,3-diazinanil ring, piperazinyl ring, azepanyl ring, tetrahydropyranyl ring, morpholino ring, 1,4-oxazepanyl ring, or 1,4-thiazepanyl ring). The non-aromatic heterocyclic ring (including the heterocycloalkyl ring or the heterocycloalkenyl ring) has one or more (e.g., 1 or 2) ring heteroatoms selected from nitrogen, oxygen, and sulfur, but all the remaining ring atoms are carbon atoms, and any nitrogen ring atom (if present) and / or any sulfur ring atom (if present) may be oxidized, and one or more carbon ring atoms may be oxidized (i.e., to form an oxo group). Even more preferably, the heterocyclic ring (including the heterocycloalkyl ring or the heterocycloalkenyl ring) has one or more (e.g., 1 or 2) nitrogen ring atoms, but all the remaining ring atoms are carbon atoms, and one or more carbon ring atoms may be oxidized, and corresponding examples particularly include pyrrolidinyl ring, piperidinyl ring, 1,3-diazinanil ring, piperazinyl ring, or azepanyl ring. A particularly preferred example of the heterocyclic ring (or the heterocycloalkyl ring) is a pyrrolidinyl ring.

[0064] Preferably, ring B is a non-aromatic 4- to 8-membered heterocyclic ring (e.g., a 4- to 8-membered heterocycloalkyl ring or a 4- to 8-membered heterocycloalkenyl ring), and the heterocyclic ring may be substituted with one or more groups R Y More preferably, ring B is substituted with one or more R YA non-aromatic 5- to 7-membered heterocyclic ring (e.g., a heterocycloalkyl ring having 5, 6, or 7 ring members, or a heterocycloalkenyl ring having 5, 6, or 7 ring members) which may be substituted with Y A 5- to 7-membered heterocycloalkyl ring which may be substituted with Y A 5- to 7-membered heterocycloalkyl ring which may be substituted with 1 wherein the heterocycloalkyl ring has 1 or 2 ring heteroatoms (preferably 1 or 2 nitrogen ring atoms) selected from nitrogen, oxygen, and sulfur, and all the remaining ring atoms are carbon atoms, and 1 or more carbon ring atoms may be oxidized. Corresponding preferred examples include a pyrrolidinyl ring, a piperidinyl ring, a 1,3-diazinanil ring, a morpholinyl ring, or an azepanyl ring, particularly a pyrrolidinyl ring or a piperidinyl ring, and even more preferably a pyrrolidinyl ring. For each of the aforementioned preferred definitions of ring B, ring B contains at least 1 nitrogen ring atom, and the group R Y is more preferably bonded to the nitrogen ring atom. Accordingly, particularly preferred examples of ring B are a pyrrolidinyl ring or a piperidinyl ring, and the pyrrolidinyl ring or the piperidinyl ring may be substituted with 1 or more R 1 and the group R Y is bonded to the nitrogen ring atom of the pyrrolidinyl ring or the piperidinyl ring. Even more preferred examples of ring B are a pyrrolidinyl ring (which may be substituted with 1 or more R 1 and the group R

[0065] According to the above general and preferred definitions of ring B, ring B is a group of the following formula (B1), even more preferably a group of the following formula (B2), and still more preferably a group of the following formula (B3):

[0066]

Chemical formula

[0067] is particularly preferred. The groups depicted above in formulas (B1), (B2) and (B3) are condensed to ring D via two adjacent ring carbon atoms (i.e., the two ring carbon atoms between Y2 and Y3 in formula (B1), the two ring carbon atoms between Y2 and N(-R 1 ), or the two ring carbon atoms between C(-R 2A )(-R 2B ) and N(-R 1 ), which is understood to be reflected in formulas (B1), (B2) and (B3) by the bonds (broken by the wavy lines) extending from these adjacent ring carbon atoms.

[0068] Y1, Y2 (when present) and Y3 (when present) are each independently selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, -SO-, -SO2-, -CO-, -NH-, and -N(C 1~5 alkyl)-, wherein said -CH2- and said -CH2-CH2- may each be substituted with one or more groups R Y , said -NH- may be substituted with a group R Y , and further, one -CH2- unit in said -CH2-CH2- may be replaced by a group selected from -O-, -S-, -SO-, -SO2-, -CO-, -NH-, and -N(C 1~5 alkyl)-, provided that formula (B1) has 4 to 8 ring atoms (i.e., the options for Y1, Y2 and Y3 in formula (B1) are limited by the additional requirement that the resulting ring B is a 4- to 8-membered ring). In particular, said -CH2- may be substituted with 1 or 2 groups R Y , and said -CH2-CH2- may be substituted with 1, 2, 3 or 4 groups R YIt may be replaced. The definitions of Y1, Y2 and Y3 apply only as long as these groups are present in the compound of formula (I), and it should be understood that whether or not this is clearly reflected by the term "when present" in the definitions of Y1, Y2 and Y3 is immaterial. Thus, the definition of Y1 applies to each of formulas (B1), (B2) and (B3), the definition of Y2 applies only to formulas (B1) and (B2), and the definition of Y3 applies only to formula (B1).

[0069] Preferably, Y1, Y2 (when present) and Y3 (when present) are each independently selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, -CO-, and -NH-, wherein each of said -CH2- and said -CH2-CH2- may be substituted with one or more (e.g., 1 or 2) groups R Y and said -NH- may be substituted with group R Y and one -CH2- unit in said -CH2-CH2- may be replaced by a group selected from -O-, -S-, and -CO-, provided that formula (B1) has 4 to 8 ring atoms. More preferably, Y1, Y2 (when present) and Y3 (when present) are each independently selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, and -CO-, wherein each of said -CH2- and said -CH2-CH2- may be substituted with one or more (e.g., 1 or 2) groups R Y provided that formula (B1) has 4 to 8 ring atoms. Even more preferably, Y1, Y2 (when present) and Y3 (when present) are each independently selected from a bond, -CH2-, and -CH2-CH2-, wherein said -CH2- may be substituted with 1 or 2 groups R Y and said -CH2-CH2- may be substituted with 1, 2, 3 or 4 groups R Y provided that formula (B1) has 4 to 8 ring atoms.

[0070] In formula (B1), Y1 is selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, -CO-, and -NH-, and the -CH2- and the -CH2-CH2- may each be substituted with one or more (for example, 1 or 2) groups R Y and the -NH- may be substituted with a group R Y and one -CH2- unit in the -CH2-CH2- may be replaced by a group selected from -O-, -S-, and -CO-. Y2 and Y3 are each independently selected from a bond, -CH2-, -O-, -S-, and -CO-, and it is particularly preferable that the -CH2- may be substituted with 1 or 2 groups R Y More preferably, Y1 in formula (B1) is selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, and -CO-, the -CH2- and the -CH2-CH2- may each be substituted with one or more (for example, 1 or 2) groups R Y and Y2 and Y3 in formula (B1) are each independently a bond or -CH2-, and the -CH2- may be substituted with 1 or 2 groups R Y

[0071] In formula (B2), Y1 and Y2 are each independently selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, -CO-, and -NH-, the -CH2- and the -CH2-CH2- may each be substituted with one or more (for example, 1 or 2) groups R Y and the -NH- may be substituted with a group R Y and it is preferable that one -CH2- unit in the -CH2-CH2- may be replaced by a group selected from -O-, -S-, and -CO-. More preferably, Y1 and Y2 in formula (B2) are each independently selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, and -CO-, the -CH2- and the -CH2-CH2- may each be substituted with one or more (for example, 1 or 2) groups R Y ​It may be replaced by. More preferably, Y1 and Y2 in formula (B2) are each independently selected from a bond, -CH2-, and -CH2-CH2-, and said -CH2- is one or two groups R Y It may be substituted with, and said -CH2-CH2- is one, two, three or four groups R Y It may be substituted with.

[0072] In formula (B3), Y1 is selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, -CO-, and -NH-, and said -CH2- and said -CH2-CH2- are each one or more (for example, one or two) groups R Y It may be substituted with, and said -NH- is a group R Y It may be substituted with, and preferably one -CH2- unit in said -CH2-CH2- may be replaced by a group selected from -O-, -S-, and -CO-. More preferably, Y1 in formula (B3) is selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, and -CO-, and said -CH2- and said -CH2-CH2- are each one or more (for example, one or two) groups R Y It may be substituted with. Even more preferably, Y1 in formula (B3) is selected from a bond, -CH2-, and -CH2-CH2-, said -CH2- is one or two groups R Y It may be substituted with, and said -CH2-CH2- is one, two, three or four groups R Y It may be substituted with. Still even more preferably, Y1 in formula (B3) is -CH2- or -CH2-CH2-, said -CH2- is one or two groups R Y It may be substituted with, and said -CH2-CH2- is one, two, three or four groups R Y It may be substituted with. Even more preferably, Y1 in formula (B3) is -CH2- which may be substituted with one or two groups R Y It is.

[0073] Therefore, ring B is one or two groups R YA group of the following formula which may be replaced by:

[0074] [Chemical Formula]

[0075] is particularly preferred. The said formula (i.e., ring B) may be substituted with 0, 1 or 2 groups R Y but this is preferably substituted with 0 or 1 group R Y and more preferably, it is not substituted with any group R Y .

[0076] Therefore, most preferably, ring B is a group of the following formula:

[0077] [Chemical Formula]

[0078] is. As described above, ring D is a 5- or 6-membered aromatic heterocyclic ring containing at least one nitrogen ring atom, and the said aromatic heterocyclic ring may be substituted with one or more groups R X . Ring D is fused to ring B, and ring D is substituted with the group -L-A, but these features are also depicted in formula (I), and it should be understood that ring D is not necessarily repeated in all cases further described herein below.

[0079] Preferably, ring D is a 5- or 6-membered aromatic heterocyclic ring having 1, 2 or 3 ring heteroatoms independently selected from nitrogen, oxygen and sulfur, at least one of the said ring heteroatoms being a nitrogen ring atom (preferably all ring heteroatoms being nitrogen ring atoms), and all the remaining ring atoms being carbon atoms, and the said aromatic heterocyclic ring may be substituted with one or more groups R XIt may be replaced by. Preferred corresponding examples of ring D include a pyridinyl ring, a pyridazinyl ring, a pyrimidinyl ring, a pyrazinyl ring, a 1,2,4 - triazinyl ring, a 1H - pyrrolyl ring, a pyrazolyl ring, an imidazolyl ring, a 1,2,3 - triazolyl ring, a furanyl ring, a thiophenyl ring, an oxazolyl ring, an isoxazolyl ring, a thiazolyl ring, or an isothiazolyl ring. In particular, ring D may contain, for example, one nitrogen ring atom and one additional ring heteroatom (preferably an additional nitrogen ring atom) selected from nitrogen, oxygen, and sulfur, and all the remaining ring atoms may be carbon atoms, and it may be a 5 - or 6 - membered aromatic heterocyclic ring, and the aromatic heterocyclic ring may have one or more groups R X It may be replaced by. More preferably, ring D is a 6 - membered aromatic heterocyclic ring containing 1, 2, or 3 nitrogen ring atoms, and all the remaining ring atoms are carbon atoms, and the aromatic heterocyclic ring may have one or more groups R X It may be replaced by. Even more preferably, ring D is a 6 - membered aromatic heterocyclic ring containing 1 or 2 nitrogen ring atoms, and all the remaining ring atoms are carbon atoms, and the aromatic heterocyclic ring may have one or more groups R X It may be replaced by, and corresponding examples particularly include a pyridinyl ring, a pyridazinyl ring, a pyrimidinyl ring, or a pyrazinyl ring. Even more preferably, ring D is a pyridinyl or pyrazinyl ring which may be replaced by one or more groups R X It may be replaced by. Still even more preferably, ring D is a pyridinyl or pyrazinyl ring which may be replaced by one or more groups R X It may be replaced by, and the pyridinyl or pyrazinyl ring is condensed to ring B via its ring carbon atoms 2 and 3. Even more preferably, ring D is a pyrazinyl ring which may be replaced by one or more groups R X It may be replaced by, and the pyrazinyl ring is condensed to ring B via its ring carbon atoms 2 and 3. Ring D may have 0, 1, or 2 groups R X , more preferably 0 or 1 group R X It is even more preferably replaced by, and still even more preferably, ring D is not replaced by any group R X .

[0080] As depicted in formula (I), the group -L-A is attached to ring D. The group -L-A may in principle be attached to any ring atom of ring D (other than the two ring atoms shared by rings B and D), but in the case of a 5-membered aromatic heterocycle as ring D, -L-A is preferably attached to the ring atom of said 5-membered aromatic heterocycle that is furthest from the two ring atoms shared by rings B and D. In the case of a 6-membered aromatic heterocycle as ring D, -L-A is preferably attached to one of the two ring atoms of said 6-membered aromatic heterocycle that is furthest from the two ring atoms shared by rings B and D, more preferably to the ring atom (among the aforementioned two ring atoms that is furthest from the two ring atoms shared by rings B and D) that is closer to (i.e., more proximate to) the ring atom of ring B having groups R 2A and R 2B than the other of the aforementioned two ring atoms that is furthest from the two ring atoms shared by rings B and D).

[0081] According to the above general and preferred definitions of ring D, ring D is a group of the following formula (D1):

[0082]

Chemical formula

[0083] [wherein the ring atoms X1, X2, X3 and X4 are each independently a carbon atom or a nitrogen atom, one of X2 and X3 is a carbon atom and has the group -L-A, at least one of the remaining ring atoms of X1, X2, X3 and X4 is a nitrogen atom, and those of the ring atoms X1, X2, X3 and X4 that are carbon atoms (and do not have the group -L-A) may particularly preferably be substituted with the group R X [] is.

[0084] The group depicted above in formula (D1) is fused to ring B via two adjacent ring carbon atoms (other than X1 to X4), which is understood to be reflected in formula (D1) by the bond(s) extending from (and being interrupted by the wavy line) these adjacent ring carbon atoms. Any of X1, X2, X3 and X4 may be the group RX When it is a carbon atom substituted by, the group R X Otherwise (i.e., in the absence of any optional substituent R X ), it will be further understood that it exchanges the hydrogen atoms bonded to each carbon atom. Further, it will be understood that those of the ring atoms X1, X2, X3 and X4 that are nitrogen atoms have no any optional substituents.

[0085] In formula (D1), one or two of the ring atoms X1, X2, X3 and X4 are each a nitrogen atom, and all the remaining ring atoms (among X1, X2, X3 and X4) are carbon atoms, whereby it is preferable that one of X2 and X3 is a carbon atom having the group -L-A. For example, X1 may be a nitrogen atom, but all the remaining ring atoms X2, X3 and X4 are carbon atoms (whereby one of X2 and X3 is a carbon atom having the group -L-A), or X4 may be a nitrogen atom, but all the remaining ring atoms X1, X2 and X3 are carbon atoms (whereby one of X2 and X3 is a carbon atom having the group -L-A), or X1 and X4 may be nitrogen atoms, but the remaining ring atoms X2 and X3 are carbon atoms (whereby one of X2 and X3 is a carbon atom having the group -L-A). More preferably, X1 is a nitrogen atom, one of X2, X3 and X4 is a nitrogen atom or a carbon atom, and the other two of X2, X3 and X4 are each a carbon atom, whereby one of X2 and X3 is a carbon atom having the group -L-A. Even more preferably, X1 is a nitrogen atom, X4 is a nitrogen atom or a carbon atom, and X2 and X3 are each a carbon atom, whereby one of X2 and X3 is a carbon atom having the group -L-A. Still even more preferably, X1 and X4 are each a nitrogen atom, and X2 and X3 are each a carbon atom, whereby the carbon atom in either X2 or X3 has the group -L-A. As described above, the compound of formula (I) has 0, 1 or 2 groups R X , more preferably 0 or 1 group RX and more preferably zero (i.e., absent) groups R X are preferably included. Thus, X1 and X4 are each a nitrogen atom, and particularly preferably, one of X2 and X3 is C(−L−A) and the other of X2 and X3 is C(−H).

[0086] Even more preferably, ring D is a group of the following formula (D2):

[0087]

Chemical formula

[0088] (wherein ring atoms X1, X3 and X4 are each independently a carbon atom or a nitrogen atom, at least one of X1, X3 and X4 is a nitrogen atom, and those of ring atoms X1, X3 and X4 which are carbon atoms may be substituted with group R X ). is.

[0089] Preferably, one or two of ring atoms X1, X3 and X4 are each a nitrogen atom, and all the remaining ring atoms (among X1, X3 and X4) are carbon atoms. More preferably, X1 is a nitrogen atom, one of X3 and X4 is a nitrogen atom or a carbon atom, and the other of X3 and X4 is a carbon atom. Thus, for example, X1 may be a nitrogen atom, and X3 and X4 may each be a carbon atom, or alternatively, X1 and X3 may each be a nitrogen atom, and X4 may be a carbon atom, or alternatively, X1 and X4 may each be a nitrogen atom, and X3 may be a carbon atom. It is particularly preferred that X1 and X4 are each a nitrogen atom and X3 is a carbon atom. As described above, those of ring atoms X1, X3 and X4 which are carbon atoms may be substituted with group R X . However, the compound of formula (I) has 0, 1 or 2 groups R X , more preferably 0 or 1 group RX , more preferably 0 groups R X are included, and as a result, among the ring atoms X1, X3 and X4 that are carbon atoms, preferably, the group R X is not substituted, that is, it is preferably a ring atom C(-H). Therefore, X1 and X4 are each a nitrogen atom, and X3 is a carbon atom that may be substituted with R X is particularly preferably, and more preferably, X1 and X4 are each N, and X3 is C(-H).

[0090] Therefore, more preferably, ring D is a group of the following formula (D3):

[0091]

Chemical formula

[0092] is as follows. According to the above definitions of rings B and D, the compound of formula (I) has the following structure:

[0093]

Chemical formula

[0094] has, and more preferably, the compound of formula (I) has the following structure:

[0095]

Chemical formula

[0096] has, and even more preferably, the compound of formula (I) has the following structure:

[0097]

Chemical formula

[0098] has, and still more preferably, the compound of formula (I) has the following structure:

[0099]

Chem.

[0100] has, and more preferably, the compound of formula (I) has the following structure:

[0101]

Chem.

[0102] It is particularly preferred to have. In formula (I), the group R 1 is selected from C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~5 alkylene)-carbocyclic, and -(C 0~5 alkylene)-heterocyclic, and the alkylene groups in the alkyl, the alkenyl, the alkynyl, the -(C 0~5 alkylene)-carbocyclic, and the alkylene groups in the -(C 0~5 alkylene)-heterocyclic may each be substituted with one or more (e.g., 1, 2, or 3) groups R 12 , and one or more (e.g., 1, 2, or 3) -CH2- units contained in the alkylene groups in the alkyl, the alkenyl, the alkynyl, the -(C 0~5 alkylene)-carbocyclic, or the alkylene groups in the -(C 0~5 alkylene)-heterocyclic may each be replaced by a group independently selected from -C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, and each R L1 is independently hydrogen or C 1~5 alkyl, and two groups R L1may also join to each other and together with the carbon atoms to which they are attached to form a cycloalkyl or heterocycloalkyl, and said -(C 0~5 The carbocyclic group in (alkylene)-carbocyclic and said -(C 0~5 The heterocyclic group in (alkylene)-heterocyclic may each be substituted with one or more (e.g., 1, 2, 3, or 4) groups R 11 .

[0103] Preferably, R 1 is selected from C 1~5 alkyl, -(C 0~5 alkylene)-carbocyclic, and -(C 0~5 alkylene)-heterocyclic, and the alkylene group in said alkyl, said -(C 0~5 alkylene)-carbocyclic, and the alkylene group in said -(C 0~5 alkylene)-heterocyclic may each be substituted with one or more groups R 12 , and one or more -CH2- units contained in the alkylene group in said alkyl, said -(C 0~5 alkylene)-carbocyclic, or said -(C 0~5 alkylene)-heterocyclic may each be replaced by a group independently selected from -C(R L1 )(R L1 ), -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 ), and each R L1 is independently hydrogen or C 1~5 alkyl, and two groups R L1 attached to the same carbon atom may also join to each other and together with the carbon atom to which they are attached to form a cycloalkyl (e.g., C 3~6 cycloalkyl) or heterocycloalkyl (e.g., 3- to 6-membered heterocycloalkyl), and the carbocyclic group in said -(C 0~5 alkylene)-carbocyclic and said -(C 0~5The heterocyclic group in (alkylene)-heterocyclyl may each be substituted with one or more groups R 11 optionally.

[0104] More preferably, R 1 is C 1~5 alkyl (e.g., isobutyl), -(C 0~5 alkylene)-carbocyclyl, and -(C 0~5 alkylene)-heterocyclyl, wherein the alkylene group in the -(C 0~5 alkylene)-carbocyclyl and the alkylene group in the -(C 0~5 alkylene)-heterocyclyl may each be substituted with one or more groups R 12 optionally, and one or more -CH2- units contained in the alkylene group in the -(C 0~5 alkylene)-carbocyclyl or the alkylene group in the -(C 0~5 alkylene)-heterocyclyl may each be replaced by a group independently selected from -C(R L1 )(R L1 ), -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, each R L1 is independently hydrogen or C 1~5 alkyl, and two groups R L1 bonded to the same carbon atom may also be joined to each other to form cycloalkyl or heterocycloalkyl together with the carbon atom to which they are bonded, and the carbocyclyl group in the -(C 0~5 alkylene)-carbocyclyl and the heterocyclic group in the -(C 0~5 alkylene)-heterocyclyl may each be substituted with one or more groups R 11 optionally.

[0105] Even more preferably, R 1 is -L 1 -carbocyclyl or -L 1 -heterocyclyl, and the carbocyclyl in the -L 1 -carbocyclyl or the -L1 - The heterocycle in the heterocyclyl may be substituted with one or more (e.g., 1, 2, 3, or 4) groups R 11 and may be substituted.

[0106] For example, R 1 is -L 1 -aryl, -L 1 -cycloalkyl, -L 1 -cycloalkenyl, -L 1 -heteroaryl, -L 1 -heterocycloalkyl, or -L 1 -heterocycloalkenyl, and the cyclic moiety in each of the aforementioned groups may be substituted with one or more groups R 11 and may be substituted. R 1 is -L 1 -aryl, -L 1 -cycloalkyl, -L 1 -heteroaryl or -L 1 -heterocycloalkyl, and the aryl in the -L 1 -aryl, the cycloalkyl in the -L 1 -cycloalkyl, the heteroaryl in the -L 1 -heteroaryl or the heterocycloalkyl in the -L 1 -heterocycloalkyl may be particularly preferably substituted with one or more groups R 11 and may be substituted. More preferably, R 1 is -L 1 -aryl, -L 1 -cycloalkyl or -L 1 -heteroaryl, and the aryl in the -L 1 -aryl, the cycloalkyl in the -L 1 -cycloalkyl or the heteroaryl in the -L 1 -heteroaryl may be substituted with one or more groups R 11 and may be substituted. In particular, R 1 is -L 1 -phenyl, -L 1 -naphthyl (e.g., -L 1 -naphthalen-1-yl or -L 1-naphthalen-2-yl), -L 1 -(C 3~7 cycloalkyl), -L 1 -(monocyclic 5- or 6-membered heteroaryl), or -L 1 -(bicyclic 9- or 10-membered heteroaryl), and the cyclic moiety in each of the aforementioned groups may be substituted with one or more groups R 11 is preferably. As an example, R 1 is -L 1 -heteroaryl [e.g., -L 1 -(monocyclic 5- or 6-membered heteroaryl) or -L 1 -(bicyclic 9- or 10-membered heteroaryl)], and when the heteroaryl in the -L 1 -heteroaryl may be substituted with one or more groups R 11 , the -L 1-The heteroaryl in heteroaryl is, for example, pyrrolyl (e.g., 1H-pyrrol-1-yl, 1H-pyrrol-2-yl, or 1H-pyrrol-3-yl), pyrazolyl (e.g., pyrazol-1-yl, pyrazol-3-yl, or pyrazol-4-yl), imidazolyl (e.g., imidazol-1-yl, imidazol-2-yl, or imidazol-4-yl), triazolyl (e.g., 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, or 4H-1,2,4-triazolyl;For example, 1H-1,2,3-triazol-1-yl, 1H-1,2,3-triazol-4-yl, 1H-1,2,3-triazol-5-yl, 1H-1,2,4-triazol-1-yl, 1H-1,2,4-triazol-3-yl, or 1H-1,2,4-triazol-5-yl, etc.), furanyl (e.g., furan-2-yl or furan-3-yl), thiophenyl (e.g., thiophene-2-yl or thiophene-3-yl), oxazolyl (e.g., oxazole-2-yl, oxazole-4-yl, or oxazole-5-yl), isoxazolyl (e.g., isoxazole-3-yl, isoxazole-4-yl, or isoxazole-5-yl), thiazolyl, isothiazolyl, pyridinyl (e.g., pyridine-2-yl, pyridine-3-yl, or pyridine-4-yl), pyridazinyl, pyrimidinyl, pyrazinyl, 1H-indolyl, 2H-isoindolyl, indolizinyl (e.g., indolizin-1-yl or indolizin-2-yl), 1H-indazolyl, benzimidazolyl, benzofuranyl (e.g., benzofuran-2-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, or benzofuran-7-yl), isobenzofuranyl, benzo[b]thiophenyl (e.g., benzo[b]thiophene-2-yl, benzo[b]thiophene-3-yl, benzo[b]thiophene-4-yl, benzo[b]thiophene-5-yl, benzo[b]thiophene-6-yl, or benzo[b]thiophene-7-yl), benzo[c]thiophenyl, quinolinyl, isoquinolinyl, quinoxalinyl, phthalazinyl, quinazolinyl, and cinnolinyl may be selected. R; 1 is -L 1 -cycloalkyl [e.g., -L 1 -(C 3~7 cycloalkyl)], and the -L 1 -cycloalkyl in the -cycloalkyl may be substituted with one or more groups R 11 when this is the case, the -L 1- The cycloalkyl in cycloalkyl may be selected from, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. Even more preferably, R 1 is -L 1 -phenyl, -L 1 -(monocyclic 5- or 6-membered heteroaryl), or -L 1 -(bicyclic 9- or 10-membered heteroaryl), and the -L 1 -phenyl in -phenyl, the heteroaryl in the -L 1 -(monocyclic 5- or 6-membered heteroaryl) and the -L 1 -(bicyclic 9- or 10-membered heteroaryl) may each be substituted with one or more groups R 11 . Even more preferably, R 1 is -L 1 -phenyl, and the phenyl in the -L 1 -phenyl may be substituted with one or more (e.g., 1, 2, or 3) groups R 11 .

[0107] R 1 Further examples of R include any of the specific groups R contained in the compounds of formula (I) described in the Examples section, particularly any one of Examples 1 to 282. 1 L 1 is independently selected from a bond, -C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, and each R L1 is independently hydrogen or C 1~5 alkyl, and further, two groups R L1 bonded to the same carbon atom may also be joined to each other to form, together with the carbon atom to which they are bonded, cycloalkyl (e.g., C 3~6 cycloalkyl) or heterocycloalkyl (e.g., 3- to 6-membered heterocycloalkyl).

[0108] Preferably, L1 is independently selected from a bond, -CH2-, -CH(C 1~5 alkyl)-, -C(C 1~5 alkyl)(C 1~5 alkyl)-, C 3~6 cycloalkyl-1,1-ene, -O-, -S-, -SO-, -SO2-, -CO-, -NH-, and -N(C 1~5 alkyl)-. More preferably, L 1 is independently selected from a bond, -CH2-, -CH(C 1~5 alkyl)-, -C(C 1~5 alkyl)(C 1~5 alkyl)-, and C 3~5 cycloalkyl-1,1-ene (e.g., cyclopropyl-1,1-ene). Even more preferably, L 1 is independently selected from a bond, -CH2-, -CH(C 1~3 alkyl)-, and -C(C 1~3 alkyl)(C 1~3 alkyl)-. Still even more preferably, L 1 is a bond.

[0109] L 1 According to the above definition of L, R 1 is particularly preferably phenyl which may be substituted with one or more (e.g., 1, 2, or 3) groups R 11 . When the phenyl is optionally substituted with one group R 11 , the group R 11 is bonded to the meta or para position (preferably the para position) of the phenyl, i.e., R 1 is 3-R 11 -phenyl or 4-R 11 -phenyl (preferably 4-R 11 -phenyl). When the phenyl is optionally substituted with two groups R 11 , the two groups R 11 are bonded to the meta and para positions, i.e., R 1 is 3-R 11 -4-R 11-phenyl is preferred. When the phenyl is optionally substituted with three groups R 11 two of the three groups R 11 are bonded to the meta positions and one group R 11 is bonded to the para position, that is, R 1 is preferably 3-R 11 -4-R 11 -5-R 11 -phenyl. The phenyl is more preferably substituted with two or three (especially two) groups R 11 . Therefore, R 1 is 3-R 11 -4-R 11 -phenyl or 3-R 11 -4-R 11 -5-R 11 -phenyl, and each R 11 is independently selected from halogen (e.g., -F, -Cl, -Br, or -I), C 1~5 haloalkyl (e.g., -CF3), and C 1~5 alkyl (e.g., -CH3), and even more preferably each R 11 is particularly preferably independently selected from -F, -Cl, -CF3, and -CH3. Corresponding preferred examples of R 1 include 4-chloro-3-fluoro-phenyl, 3,4-dichloro-phenyl, 3,4-difluoro-phenyl, 3-chloro-4-fluoro-phenyl, 3-fluoro-4-trifluoromethyl-phenyl, 3-chloro-4-trifluoromethyl-phenyl, 3-fluoro-4-methyl-phenyl, 3-chloro-4-methyl-phenyl, 3,4,5-trifluoro-phenyl, or 4-chloro-3,5-difluoro-phenyl. Particularly preferred examples of R 1 are 4-chloro-3-fluoro-phenyl or 3,4-difluoro-phenyl.

[0110] Each R 11 is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~3 alkylene)-OH, -(C0~3 (Alkylene)-O(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-O(C 1~5 (Alkylene)-OH, -(C 0~3 (Alkylene)-O(C 1~5 (Alkylene)-O(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-SH, -(C 0~3 (Alkylene)-S(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-S(C 1~5 (Alkylene)-SH, -(C 0~3 (Alkylene)-S(C 1~5 (Alkylene)-S(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-NH2, -(C 0~3 (Alkylene)-NH(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-N(C 1~5 (Alkyl)(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-NH-OH, -(C 0~3 (Alkylene)-N(C 1~5 (Alkyl)-OH, -(C 0~3 (Alkylene)-NH-O(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-N(C 1~5 (Alkyl)-O(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-halogen, -(C 0~3 (Alkylene)-(C 1~5 (Haloalkyl), -(C 0~3 (Alkylene)-O-(C 1~5 (Haloalkyl), -(C 0~3 (Alkylene)-CN, -(C 0~3 (Alkylene)-CHO, -(C 0~3 (Alkylene)-CO-(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-COOH, -(C 0~3 (Alkylene)-CO-O-(C 1~5 (Alkyl), -(C 0~3(alkylene)-O-CO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-CO-NH2, -(C 0~3 (alkylene)-CO-NH(C 1~5 (alkyl), -(C 0~3 (alkylene)-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -(C 0~3 (alkylene)-NH-CO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-NH-COO(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -(C 0~3 (alkylene)-O-CO-NH(C 1~5 (alkyl), -(C 0~3 (alkylene)-O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-NH2, -(C 0~3 (alkylene)-SO2-NH(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -(C 0~3 (alkylene)-NH-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-carbocyclic, -(C 0~3 (alkylene)-heterocyclic, and -L Z -R Zselected independently from, said -(C 0~3 The carbocyclic group in alkylene)-carbocyclic and said -(C 0~3 The heterocyclic group in alkylene)-heterocyclic may each be substituted with one or more (e.g., 1, 2, or 3) groups R Cyc .

[0111] Preferably, each R 11 is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -NH-OH, -N(C 1~5 alkyl)-OH, -NH-O(C 1~5 alkyl), -N(C 1~5 alkyl)-O(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO-(C 1~5 alkyl), -COOH, -CO-O-(C 1~5 alkyl), -O-CO-(C 1~5 alkyl), -CO-NH2, -CO-NH(C 1~5 alkyl), -CO-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-CO-(C 1~5 alkyl), -N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -NH-COO(C 1~5 alkyl), -N(C 1~5(alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), -SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-carbocyclic, -(C 0~3 (alkylene)-heterocyclic, and -L Z -R Z is independently selected from, said -(C 0~3 The carbocyclic group in (alkylene)-carbocyclic and said -(C 0~3 The heterocyclic group in (alkylene)-heterocyclic may each be substituted with one or more groups R Cyc More preferably, each R 11 is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, halogen, C 1~5 haloalkyl, -O-(C 1~5 (haloalkyl), -CN, -(C 0~3 (alkylene)-carbocyclic, and -(C 0~3 (alkylene)-heterocyclic is independently selected from, said -(C 0~3 The carbocyclic group in (alkylene)-carbocyclic and said -(C 0~3 The heterocyclic group in (alkylene)-heterocyclic is each C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, halogen, C 1~5 haloalkyl, -O-(C 1~5It may be substituted with one or more groups independently selected from haloalkyl) and -CN. Even more preferably, each R 11 is C 1~5 alkyl, halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN. Even still more preferably, each R 11 is halogen (e.g., -F, -Cl, -Br, or -I), C 1~5 haloalkyl (e.g., -CF3), and C 1~5 alkyl (e.g., methyl). Even more preferably, each R 11 is independently halogen (especially -F or -Cl) or C 1~5 haloalkyl (especially -CF3).

[0112] Each R 12 is -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -NH-OH, -N(C 1~5 alkyl)-OH, -NH-O(C 1~5 alkyl), -N(C 1~5 alkyl)-O(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO-(C 1~5 alkyl), -COOH, -CO-O-(C 1~5 alkyl), -O-CO-(C 1~5 alkyl), -CO-NH2, -CO-NH(C 1~5 alkyl), -CO-N(C1~5 (alkyl)(C 1~5 (alkyl), -NH-CO-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -NH-COO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), -SO2-(C 1~5 (alkyl), carbocyclic, heterocyclic, and -L Z -R Z independently selected from, said carbocyclic and said heterocyclic are each optionally substituted with one or more (e.g., 1, 2, or 3) groups R Cyc .

[0113] Preferably, each R 12 is -OH, -O(C 1~5 (alkyl), -O(C 1~5 (alkylene)-OH, -O(C 1~5 (alkylene)-O(C 1~5 (alkyl), -SH, -S(C 1~5 (alkyl), -S(C 1~5 (alkylene)-SH, -S(C 1~5 (alkylene)-S(C 1~5 (alkyl), -NH2, -NH(C 1~5 (alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-OH, -N(C 1~5 (alkyl)-OH, -NH-O(C 1~5(alkyl), -N(C 1~5 (alkyl)-O(C 1~5 (alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO-(C 1~5 (alkyl), -COOH, -CO-O-(C 1~5 (alkyl), -O-CO-(C 1~5 (alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-CO-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -NH-COO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), and -SO2-(C 1~5 (alkyl) and is independently selected from. More preferably, each R 12 is -OH, -O(C 1~5 (alkyl), -SH, -S(C 1~5 (alkyl), -NH2, -NH(C 1~5 (alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN and is independently selected from.

[0114] R2A and R 2B are joined to each other and together with the carbon atoms to which they are attached form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, said cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl being optionally substituted with one or more (e.g., 1, 2 or 3) groups R 21 or alternatively, R 2A and R 2B are each independently selected from C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~5 alkylene)-carbocyclic, and -(C 0~5 alkylene)-heterocyclic, the alkylene groups in said alkyl, said alkenyl, said alkynyl, said -(C 0~5 alkylene)-carbocyclic, and the alkylene groups in said -(C 0~5 alkylene)-heterocyclic each being optionally substituted with one or more groups R 22 and one or more of the -CH2- units contained in the alkylene groups in said alkyl, said alkenyl, said alkynyl, said -(C 0~5 alkylene)-carbocyclic, or said -(C 0~5 alkylene)-heterocyclic each being optionally replaced by a group independently selected from -O-, -NH-, -N(C 1~5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, the carbocyclic groups in said -(C 0~5 alkylene)-carbocyclic and the heterocyclic groups in said -(C 0~5 alkylene)-heterocyclic each being optionally substituted with one or more groups R Cyc or R 2A and group R Y(when present) may also be joined together to form, together with the ring atoms to which they are attached, a carbocyclic or heterocyclic ring, said carbocyclic or said heterocyclic ring being optionally substituted with one or more (e.g., 1, 2 or 3) groups R Cyc and may be substituted with.

[0115] As described above, R 2A and R 2B may be joined together to form, together with the carbon atoms to which they are attached, a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, said cycloalkyl, said cycloalkenyl, said heterocycloalkyl or said heterocycloalkenyl being optionally substituted with one or more groups R 21 and may be substituted with. It will be appreciated that said cycloalkyl, said cycloalkenyl, said heterocycloalkyl or said heterocycloalkenyl may form a spirocyclic ring system together with fused rings B and D. Said cycloalkyl (formed from the carbon atoms having R 2A , R 2B as well as R 2A and R 2B ) is preferably a monocyclic cycloalkyl, more preferably a C 3~7 cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl), and a particularly preferred example of said cycloalkyl is cyclopentyl. Said cycloalkenyl (formed from the carbon atoms having R 2A , R 2B as well as R 2A and R 2B ) is preferably a monocyclic cycloalkenyl, more preferably a C 4~7 cycloalkenyl (e.g., cyclobutenyl, cyclopentenyl, cyclohexenyl, or cycloheptenyl), and particularly preferred examples of said cycloalkenyl are cyclobutenyl or cyclopentenyl. Said heterocycloalkyl (R 2A , R 2B as well as R2A and R 2B formed from carbon atoms having) is preferably a monocyclic heterocycloalkyl, more preferably a 3- to 7-membered heterocycloalkyl (e.g., containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and all remaining ring atoms being carbon atoms), even more preferably a 4- to 7-membered heterocycloalkyl having 1 ring heteroatom selected from oxygen, sulfur, and nitrogen (all other ring atoms being carbon atoms), and corresponding examples of said heterocycloalkyl include tetrahydrofuranyl (which may be bonded via a carbon ring atom at the 3-position), tetrahydropyranyl (which may be bonded via a carbon ring atom at the 4-position), tetrahydrothiophenyl (which may be bonded via a carbon ring atom at the 3-position), thianyl (which may be bonded via a carbon ring atom at the 4-position), pyrrolidinyl (which may be bonded via a carbon ring atom at the 3-position), or piperidinyl (which may be bonded via a carbon ring atom at the 4-position), and particularly preferred examples of said heterocycloalkyl are tetrahydrofuranyl (which may be bonded via a carbon ring atom at the 3-position). Said heterocycloalkenyl (R 2A , R 2B as well as R 2A and R 2B formed from carbon atoms having) is preferably a monocyclic heterocycloalkenyl, more preferably a 4- to 7-membered heterocycloalkenyl (e.g., containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and all remaining ring atoms being carbon atoms), even more preferably a 4- to 7-membered heterocycloalkenyl having 1 ring heteroatom selected from oxygen, sulfur, and nitrogen (all other ring atoms being carbon atoms). R 2A and R 2B are joined to each other and together with the carbon atoms to which they are attached form a cycloalkyl or a heterocycloalkyl, and it is particularly preferred that said cycloalkyl or said heterocycloalkyl may be substituted with one or more groups R 21 . Even more preferably, R 2Aand R 2B are joined to each other and together with the carbon atom to which they are attached form a cyclopentyl or tetrahydrofuranyl, said cyclopentyl or said tetrahydrofuranyl being optionally substituted with one or more groups R 21 (and even more preferably, R 2A and R 2B are joined to each other and together with the carbon atom to which they are attached form a cyclopentyl which may be optionally substituted with one or more groups R 21 ), thus, according to the above preferred definitions of ring B and ring D, the compound of formula (I) has one of the following structures:

[0116]

Chemical formula

[0117] and the cyclopentyl ring and the tetrahydrofuran ring in the formula depicted above are each particularly preferably optionally substituted with one or more groups R 21 . In this case, according to the above preferred definitions of ring B and ring D, the compound of formula (I) has one of the following structures:

[0118]

Chemical formula

[0119] and the cyclopentyl ring and the tetrahydrofuran ring in the formula depicted above are each even more preferably optionally substituted with one or more groups R 21 , and even more preferably, the compound of formula (I) has one of the following structures:

[0120]

Chemical formula

[0121] and the cyclopentyl ring in the formula depicted above is substituted with one or more groups R21 may be replaced. or (i.e., when R 2A and R 2B are not joined to each other), the groups R 2A and R 2B are each independently selected from C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~5 alkylene)-carbocyclic, and -(C 0~5 alkylene)-heterocyclic, wherein the alkylene groups in said alkyl, said alkenyl, said alkynyl, said -(C 0~5 alkylene)-carbocyclic, and the alkylene group in said -(C 0~5 alkylene)-heterocyclic may each be substituted with one or more (e.g., 1, 2, or 3) groups R 22 , and one or more (e.g., 1, 2, or 3) -CH2- units contained in the alkylene group in said alkyl, said alkenyl, said alkynyl, said -(C 0~5 alkylene)-carbocyclic, or the alkylene group in said -(C 0~5 alkylene)-heterocyclic may each be replaced by a group independently selected from -O-, -NH-, -N(C 1~5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, the carbocyclic group in said -(C 0~5 alkylene)-carbocyclic and the heterocyclic group in said -(C 0~5 alkylene)-heterocyclic may each be substituted with one or more (e.g., 1, 2, or 3) groups R Cyc .

[0122] R 2A and R 2B are not joined to each other, R 2A and R 2B are C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~5(alkylene)-carbocyclic, and -(C 0~5 independently selected from (alkylene)-heterocyclic, wherein said alkyl, said alkenyl, said alkynyl, said -(C 0~5 the alkylene group in (alkylene)-carbocyclic, and said -(C 0~5 the alkylene group in (alkylene)-heterocyclic are each independently -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN, and may be substituted with one or more (e.g., 1, 2, or 3) groups independently selected therefrom, said alkyl, said alkenyl, said alkynyl, said -(C 0~5 the alkylene group in (alkylene)-carbocyclic, or the alkylene group in said -(C 0~5 (alkylene)-heterocyclic containing one or more (e.g., 1, 2, or 3) -CH2- units may each be replaced by a group independently selected from -O-, -NH-, -N(C 1~5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, the carbocyclic group in said -(C 0~5 alkylene)-carbocyclic and the heterocyclic group in said -(C 0~5 (alkylene)-heterocyclic are each preferably substituted with one or more (e.g., 1, 2, or 3) groups R Cyc . More preferably, R 2A and R 2B are each independently selected from C 1~5 alkyl, -(C 0~5 alkylene)-cycloalkyl, -(C 0~5 alkylene)-aryl, -(C 0~5 alkylene)-heterocycloalkyl, and -(C 0~5 alkylene)-heteroaryl, said alkyl or said -(C0~5 -(C alkylene)-cycloalkyl, said -(C 0~5 alkylene)-aryl, said -(C 0~5 alkylene)-heterocycloalkyl, or said -(C 0~5 alkylene)-heteroaryl, the alkylene group in any of them is -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN, and may be substituted with one or more groups independently selected therefrom, said alkyl or said -(C 0~5 alkylene)-cycloalkyl, said -(C 0~5 alkylene)-aryl, said -(C 0~5 alkylene)-heterocycloalkyl, or said -(C 0~5 alkylene)-heteroaryl, one or more -CH2- units contained in the alkylene group in any of them may each be replaced by a group independently selected from -O-, -NH-, -N(C 1~5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, the cycloalkyl group in said -(C 0~5 alkylene)-cycloalkyl, the aryl group in said -(C 0~5 alkylene)-aryl, the heterocycloalkyl group in said -(C 0~5 alkylene)-heterocycloalkyl, and the heteroaryl group in said -(C 0~5 alkylene)-heteroaryl may each be substituted with one or more groups R Cyc . Even more preferably, R 2A and R 2B are C 1~5 alkyl, -(C 0~5 alkylene)-cycloalkyl, -(C 0~5 alkylene)-aryl (e.g., -(C such as -CH2-phenyl 0~5-(alkylene)-phenyl), -(C 0~5 -(alkylene)-heterocycloalkyl, and -(C 0~5 -(alkylene)-heteroaryl, each independently selected, wherein the alkyl or the -(C 0~5 -(alkylene)-cycloalkyl, the -(C 0~5 -(alkylene)-aryl, the -(C 0~5 -(alkylene)-heterocycloalkyl, or the -(C 0~5 -(alkylene)-heteroaryl, the alkylene group in any of which may be substituted with one or more groups independently selected from -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN, and further, the cycloalkyl group in the -(C 0~5 -(alkylene)-cycloalkyl, the aryl group in the -(C 0~5 -(alkylene)-aryl, the heterocycloalkyl group in the -(C 0~5 -(alkylene)-heterocycloalkyl, and the heteroaryl group in the -(C 0~5 -(alkylene)-heteroaryl may each be substituted with one or more groups independently selected from C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN. Even more preferably, R 2A and R 2B are C 1~5 alkyl, -(C0~3 (alkylene)-cycloalkyl (e.g., cyclopropyl, -CH2-cyclopropyl, cyclobutyl, -CH2-cyclobutyl, cyclopentyl, or -CH2-cyclopentyl), -(C 0~3 (alkylene)-heterocycloalkyl [e.g., oxetanyl (such as oxetan-2-yl or oxetan-3-yl), -CH2-oxetanyl (such as oxetan-2-ylmethyl or oxetan-3-ylmethyl), tetrahydrofuranyl (such as tetrahydrofuran-3-yl), -CH2-tetrahydrofuranyl (such as tetrahydrofuran-3-ylmethyl), tetrahydropyranyl (such as tetrahydropyran-4-yl), or -CH2-tetrahydropyranyl (such as tetrahydropyran-4-ylmethyl)], or -(C 0~3 (alkylene)-heteroaryl [e.g., -CH2-oxazolyl (such as oxazol-2-ylmethyl, oxazol-4-ylmethyl, or oxazol-5-ylmethyl), -CH2-pyridinyl (such as pyridin-2-ylmethyl, pyridin-3-ylmethyl, or pyridin-4-ylmethyl), -C(-CH3)(-CH3)-pyridinyl (-C(-CH3)(-CH3)-(pyridin-2-yl) etc.), -CH2-pyrimidinyl (such as pyrimidin-2-ylmethyl), -CH2-pyrazinyl (such as pyrazin-2-ylmethyl)] are each independently selected, and said alkyl is substituted with one or more groups independently selected from -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN, and further, the cycloalkyl group in said -(C 0~3 alkylene)-cycloalkyl, the heterocycloalkyl group in said -(C 0~3 alkylene)-heterocycloalkyl and the heteroaryl group in said -(C 0~3 alkylene)-heteroaryl are each, C1~5 alkyl, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN, and may be substituted with one or more groups independently selected therefrom. Thus, for example, R 2A and R 2B may each independently be C 1~5 alkyl, and the C 1~5 alkyl may be -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN, and may be substituted with one or more groups independently selected therefrom. Preferred corresponding examples of R 2A and / or R 2B are C 1~5 alkyl substituted with one or two groups -O(C 1~5 alkyl) (e.g., tert-butyl), such as -C(-CH3)(-CH3)-CH2-O-CH3, -C(-CH3)(-CH3)-CH2-O-CH2-CH3, -CH(-CH2-O-CH3)(-CH2-O-CH3), -CH(-CH3)-CH2-O-CH3, -CH2CH2-O-CH3, or -CH2CH2-O-CH2CH3, etc. Further examples of R 2A and / or R 2B are -(C 0~3 alkylene)-phenyl, and the -(C 0~3 alkylene)-phenyl is C 1~5 alkyl, halogen, C 1~5 haloalkyl, -O-(C 1~5is optionally substituted with one or more groups independently selected from haloalkyl), and -CN, and in particular is 4-chloro-3-fluorophenyl or 4-chloro-3-fluorophenylmethyl. Thus, for example, R 2A may be 4-chloro-3-fluorophenyl, and R 2B may be C 1~5 alkyl (e.g., methyl). Each particularly preferred example of R 2A and R 2B is methyl, ethyl, isopropyl, isobutyl, sec-butyl (e.g., (S)-sec-butyl or (R)-sec-butyl), tert-butyl, cyclopropylmethyl, 1-methylcyclobutyl, 3-(methoxymethyl)cyclobutylmethyl, 2,2,2-trifluoroethyl , -C(-CH3)(-CH3)-CH2-O-CH3, -C(-CH3)(-CH3)-CH2-O-CH2-CH3, -CH(-CH3)-CH2-O-CH3 (e.g., (S)-CH(-CH3)-CH2-O-CH3 or (R)-CH(-CH3)-CH2-O-CH3), -CH2CH2-O-CH3, -CH(-CH2-O-CH3)(-CH2-O-CH3), -CH2-(cyclobuta-1,3-diyl)-CH2-O-CH3, pyridin-2-ylmethyl, 6-methoxypyridin-2-ylmethyl, or 1-methyl-1-(pyridin-2-yl)ethyl. Even more preferably, R 2A and R 2B are each independently C 1~5 alkyl (e.g., methyl, ethyl, isopropyl, isobutyl, sec-butyl, or tert-butyl). Thus, as particularly preferred examples, R 2A and R 2B may each be methyl. It will be understood that for each of the general and preferred definitions of R 2A and R 2B described above herein, the groups R 2A and R 2B may be the same or different.

[0123] Furthermore, as described above, the group R 2A also is the group R Y (when present; preferably, the group R 2A bonded to a ring atom directly adjacent to the carbocyclic atom having R Y ) which joins with each other to form, together with the ring atom to which the groups R 2A and R Y are bonded, a carbocyclyl or a heterocyclyl, and the carbocyclyl or the heterocyclyl may be substituted with one or more (e.g., 1, 2 or 3) groups R Cyc . In particular, the group R 2A may join with the group R Y (when present), and the group R Y is bonded to a ring atom directly adjacent to the carbocyclic atom having R 2A to form, together with the ring atom to which the groups R 2A and R Y are bonded, a carbocyclyl or a heterocyclyl, and the carbocyclyl or the heterocyclyl may be substituted with one or more groups R Cyc , and the corresponding carbocyclyl or heterocyclyl is fused to ring B, and it will be appreciated that ring B together with ring D gives rise to a fused tricyclic ring system. The carbocyclyl formed from the groups R 2A and R Y (and from the ring atoms to which these groups R 2A and R Y are bonded) may be, for example, cycloalkyl, cycloalkenyl, or aryl, and preferably, the carbocyclyl is cycloalkyl, such as cyclopentyl or cyclohexyl. The carbocyclyl formed from the groups R 2A and R Y (and from the ring atoms to which these groups R 2A and R YThe heterocyclyl formed (from the ring atoms to which it is attached) may be, for example, heterocycloalkyl, heterocycloalkenyl, or heteroaryl, and preferably, the heterocyclyl is heterocycloalkyl, such as tetrahydrofuranyl (which may be attached, for example, via the ring carbon atoms in the 2- and 3-positions). Thus, R 2A and group R Y (preferably, R 2A is attached to a ring atom directly adjacent to the carbocyclic atom having R Y ) are joined to each other, they are joined to each other and together with the ring atoms to which they are attached to form cycloalkyl or heterocycloalkyl, and it is particularly preferred that the cycloalkyl or the heterocycloalkyl may be substituted with one or more groups R Cyc . R 2A and group R Y are joined to each other, it will be understood that group R 2B has the same meaning as described above herein (refer to the general and preferred meanings of R 2A and R 2B when they are not joined to each other for R 2B ).

[0124] Each R 21 is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~3 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-O(C 1~5 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-S(C 1~5 alkylene)-SH, -(C0~3 (Alkylene)-S(C 1~5 (Alkylene)-S(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-NH2, -(C 0~3 (Alkylene)-NH(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-N(C 1~5 (Alkyl)(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-NH-OH, -(C 0~3 (Alkylene)-N(C 1~5 (Alkyl)-OH, -(C 0~3 (Alkylene)-NH-O(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-N(C 1~5 (Alkyl)-O(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-Halogen, -(C 0~3 (Alkylene)-(C 1~5 (Haloalkyl), -(C 0~3 (Alkylene)-O-(C 1~5 (Haloalkyl), -(C 0~3 (Alkylene)-CN, -(C 0~3 (Alkylene)-CHO, -(C 0~3 (Alkylene)-CO-(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-COOH, -(C 0~3 (Alkylene)-CO-O-(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-O-CO-(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-CO-NH2, -(C 0~3 (Alkylene)-CO-NH(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-CO-N(C 1~5 (Alkyl)(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-NH-CO-(C 1~5 (Alkyl), -(C 0~3 (Alkylene)-N(C 1~5 (Alkyl)-CO-(C 1~5- (alkyl), - (C 0~3 alkylene) - NH - COO(C 1~5 alkyl), - (C 0~3 alkylene) - N(C 1~5 alkyl) - COO(C 1~5 alkyl), - (C 0~3 alkylene) - O - CO - NH(C 1~5 alkyl), - (C 0~3 alkylene) - O - CO - N(C 1~5 alkyl)(C 1~5 alkyl), - (C 0~3 alkylene) - SO2 - NH2, - (C 0~3 alkylene) - SO2 - NH(C 1~5 alkyl), - (C 0~3 alkylene) - SO2 - N(C 1~5 alkyl)(C 1~5 alkyl), - (C 0~3 alkylene) - NH - SO2 - (C 1~5 alkyl), - (C 0~3 alkylene) - N(C 1~5 alkyl) - SO2 - (C 1~5 alkyl), - (C 0~3 alkylene) - SO - (C 1~5 alkyl), - (C 0~3 alkylene) - SO2 - (C 1~5 alkyl), - (C 0~3 alkylene) - carbocyclic, - (C 0~3 alkylene) - heterocyclic, and - L Z - R Z are independently selected from, said - (C 0~3 The carbocyclic group in alkylene) - carbocyclic and the heterocyclic group in said - (C 0~3 The heterocyclic group in alkylene) - heterocyclic may each be substituted with one or more (e.g., 1, 2, or 3) groups R Cyc .

[0125] Preferably, each R 21 is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, - OH, - O(C 1~5alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -NH-OH, -N(C 1~5 alkyl)-OH, -NH-O(C 1~5 alkyl), -N(C 1~5 alkyl)-O(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO-(C 1~5 alkyl), -COOH, -CO-O-(C 1~5 alkyl), -O-CO-(C 1~5 alkyl), -CO-NH2, -CO-NH(C 1~5 alkyl), -CO-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-CO-(C 1~5 alkyl), -N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -NH-COO(C 1~5 alkyl), -N(C 1~5 alkyl)-COO(C 1~5 alkyl), -O-CO-NH(C 1~5 alkyl), -O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -SO2-NH2, -SO2-NH(C 1~5 alkyl), -SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-SO2-(C 1~5 alkyl), -N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -SO-(C 1~5(alkyl), -SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-carbocyclic, -(C 0~3 (alkylene)-heterocyclic, and -L Z -R Z is independently selected from, said -(C 0~3 the carbocyclic group in (alkylene)-carbocyclic and said -(C 0~3 the heterocyclic group in (alkylene)-heterocyclic may each be substituted with one or more groups R Cyc . More preferably, each R 21 is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -(C 0~3 (alkylene)-carbocyclic, and -(C 0~3 (alkylene)-heterocyclic is independently selected from, said -(C 0~3 the carbocyclic group in (alkylene)-carbocyclic and said -(C 0~3 the heterocyclic group in (alkylene)-heterocyclic may each be substituted with one or more groups independently selected from C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN. Even more preferably, each R 21 is C 1~5 alkyl (e.g., methyl), halogen (e.g., -F, -Cl, -Br, or -I), C 1~5 haloalkyl (e.g., -CF3), -O-(C 1~5 haloalkyl) (e.g., -OCF3), and -CN is independently selected from.

[0126] Each R 22 is -OH, -O(C 1~5 alkyl), -O(C 1~5(alkylene)-OH, -O(C 1~5 (alkylene)-O(C 1~5 (alkyl), -SH, -S(C 1~5 (alkyl), -S(C 1~5 (alkylene)-SH, -S(C 1~5 (alkylene)-S(C 1~5 (alkyl), -NH2, -NH(C 1~5 (alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-OH, -N(C 1~5 (alkyl)-OH, -NH-O(C 1~5 (alkyl), -N(C 1~5 (alkyl)-O(C 1~5 (alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO-(C 1~5 (alkyl), -COOH, -CO-O-(C 1~5 (alkyl), -O-CO-(C 1~5 (alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-CO-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -NH-COO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), -SO2-(C 1~5(alkyl), carbocyclic, heterocyclic, and -L Z -R Z is independently selected from, and said carbocyclic and said heterocyclic are each optionally substituted with one or more (e.g., 1, 2, or 3) groups R Cyc .

[0127] Preferably, each R 22 is -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -NH-OH, -N(C 1~5 alkyl)-OH, -NH-O(C 1~5 alkyl), -N(C 1~5 alkyl)-O(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO-(C 1~5 alkyl), -COOH, -CO-O-(C 1~5 alkyl), -O-CO-(C 1~5 alkyl), -CO-NH2, -CO-NH(C 1~5 alkyl), -CO-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-CO-(C 1~5 alkyl), -N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -NH-COO(C 1~5 alkyl), -N(C 1~5 alkyl)-COO(C 1~5 alkyl), -O-CO-NH(C 1~5 alkyl), -O-CO-N(C1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), and -SO2-(C 1~5 (alkyl) are independently selected. More preferably, each R 22 is -OH, -O(C 1~5 (alkyl), -SH, -S(C 1~5 (alkyl), -NH2, -NH(C 1~5 (alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN are independently selected.

[0128] Each R X is C 1~5 (alkyl), C 2~5 (alkenyl), C 2~5 (alkynyl), -(C 0~3 (alkylene)-OH, -(C 0~3 (alkylene)-O(C 1~5 (alkyl), -(C 0~3 (alkylene)-O(C 1~5 (alkylene)-OH, -(C 0~3 (alkylene)-O(C 1~5 (alkylene)-O(C 1~5 (alkyl), -(C 0~3 (alkylene)-SH, -(C 0~3 (alkylene)-S(C 1~5 (alkyl), -(C 0~3 (alkylene)-S(C 1~5 (alkylene)-SH, -(C 0~3 (alkylene)-S(C 1~5 (alkylene)-S(C 1~5 (alkyl), -(C 0~3-(alkylene)-NH2, -(C 0~3 -(alkylene)-NH(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-N(C 1~5 -(alkyl)(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-NH-OH, -(C 0~3 -(alkylene)-N(C 1~5 -(alkyl)-OH, -(C 0~3 -(alkylene)-NH-O(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-N(C 1~5 -(alkyl)-O(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-halogen, -(C 0~3 -(alkylene)-(C 1~5 -(haloalkyl), -(C 0~3 -(alkylene)-O-(C 1~5 -(haloalkyl), -(C 0~3 -(alkylene)-CN, -(C 0~3 -(alkylene)-CHO, -(C 0~3 -(alkylene)-CO-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-COOH, -(C 0~3 -(alkylene)-CO-O-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-O-CO-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-CO-NH2, -(C 0~3 -(alkylene)-CO-NH(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-CO-N(C 1~5 -(alkyl)(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-NH-CO-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-N(C 1~5 -(alkyl)-CO-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-NH-COO(C 1~5 -(alkyl), -(C 0~3(alkylene)-N(C 1~5 alkyl)-COO(C 1~5 alkyl), -(C 0~3 (alkylene)-O-CO-NH(C 1~5 alkyl), -(C 0~3 (alkylene)-O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 (alkylene)-SO2-NH2, -(C 0~3 (alkylene)-SO2-NH(C 1~5 alkyl), -(C 0~3 (alkylene)-SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 (alkylene)-NH-SO2-(C 1~5 alkyl), -(C 0~3 (alkylene)-N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -(C 0~3 (alkylene)-SO-(C 1~5 alkyl), -(C 0~3 (alkylene)-SO2-(C 1~5 alkyl), -(C 0~3 (alkylene)-carbocyclic, -(C 0~3 (alkylene)-heterocyclic, and -L Z -R Z independently selected from, said -(C 0~3 the carbocyclic group in (alkylene)-carbocyclic and said -(C 0~3 the heterocyclic group in (alkylene)-heterocyclic may each be substituted with one or more (e.g., 1, 2, or 3) groups R Cyc .

[0129] Preferably, each R X is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -OH, -O(C 1~5 alkyl), -O(C 1~5 (alkylene)-OH, -O(C 1~5 (alkylene)-O(C 1~5(alkyl), -SH, -S(C 1~5 (alkyl), -S(C 1~5 (alkylene)-SH, -S(C 1~5 (alkylene)-S(C 1~5 (alkyl), -NH2, -NH(C 1~5 (alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-OH, -N(C 1~5 (alkyl)-OH, -NH-O(C 1~5 (alkyl), -N(C 1~5 (alkyl)-O(C 1~5 (alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO-(C 1~5 (alkyl), -COOH, -CO-O-(C 1~5 (alkyl), -O-CO-(C 1~5 (alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-CO-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -NH-COO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), -SO2-(C 1~5 (alkyl), -(C 0~3 (alkylene)-carbocyclic, -(C 0~3-(alkylene)-heterocyclyl, and -L Z -R Z independently selected from, said -(C 0~3 alkylene)-carbocyclyl group in the carbocyclyl group and said -(C 0~3 alkylene)-heterocyclyl group in the heterocyclyl group, each, one or more groups R Cyc may be substituted. More preferably, each R X is, C 1~5 alkyl, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -(C 0~3 alkylene)-cycloalkyl (e.g., cyclopropyl), and -(C 0~3 alkylene)-heterocycloalkyl independently selected from, said -(C 0~3 alkylene)-cycloalkyl group in the cycloalkyl group and said -(C 0~3 alkylene)-heterocycloalkyl group in the heterocycloalkyl group, each, one or more groups R Cyc may be substituted.

[0130] Each R Y is, C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~3 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-O(C 1~5 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-SH, -(C 0~3 alkylene)-S(C1~5 alkyl), -(C 0~3 alkylene)-S(C 1~5 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-NH2, -(C 0~3 alkylene)-NH(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-OH, -(C 0~3 alkylene)-N(C 1~5 alkyl)-OH, -(C 0~3 alkylene)-NH-O(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-O(C 1~5 alkyl), -(C 0~3 alkylene)-halogen, -(C 0~3 alkylene)-(C 1~5 haloalkyl), -(C 0~3 alkylene)-O-(C 1~5 haloalkyl), -(C 0~3 alkylene)-CN, -(C 0~3 alkylene)-CHO, -(C 0~3 alkylene)-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-COOH, -(C 0~3 alkylene)-CO-O-(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-CO-NH2, -(C 0~3 alkylene)-CO-NH(C 1~5 alkyl), -(C 0~3 alkylene)-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-CO-(C 1~5alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-NH-COO(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-COO(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-NH(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-NH2, -(C 0~3 alkylene)-SO2-NH(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-SO-(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-carbocyclic, -(C 0~3 alkylene)-heterocyclic, and -L Z -R Z are independently selected from, said -(C 0~3 the carbocyclic group in alkylene)-carbocyclic and said -(C 0~3 the heterocyclic group in alkylene)-heterocyclic are each optionally substituted with one or more (e.g., 1, 2 or 3) groups R Cyc and, any two groups R attached to the same ring carbon atom Y(when present) may also (i) join together to form, together with the carbon atoms to which they are attached, a cycloalkyl or heterocycloalkyl, said cycloalkyl or said heterocycloalkyl being optionally substituted with one or more (e.g., 1, 2 or 3) groups R Cyc or (ii) form a group =O with each other.

[0131] Preferably, each R Y is C 1~5 alkyl, -(C 0~3 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-NH2, -(C 0~3 alkylene)-NH(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-halogen, -(C 0~3 alkylene)-(C 1~5 haloalkyl), -(C 0~3 alkylene)-O-(C 1~5 haloalkyl), -(C 0~3 alkylene)-CN, -(C 0~3 alkylene)-CHO, -(C 0~3 alkylene)-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-COOH, -(C 0~3 alkylene)-CO-O-(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-CO-NH2, -(C 0~3 alkylene)-CO-NH(C 1~5 alkyl), -(C 0~3 alkylene)-CO-N(C 1~5(Alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -(C 0~3 alkylene)-NH-COO(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-COO(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-NH(C 1~5 alkyl), -(C 0~3 alkylene)-O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-NH2, -(C 0~3 alkylene)-SO2-NH(C 1~5 alkyl), -(C 0~3 alkylene)-SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -(C 0~3 alkylene)-aryl, -(C 0~3 alkylene)-cycloalkyl (e.g., cyclopropyl), -(C 0~3 alkylene)-heteroaryl (e.g., pyridinyl; e.g., pyridin-2-yl), and -(C 0~3 alkylene)-heterocycloalkyl, independently selected from, said -(C 0~3 aryl group in alkylene)-aryl, said -(C 0~3 cycloalkyl group in alkylene)-cycloalkyl, said -(C 0~3 heteroaryl group in alkylene)-heteroaryl, and said -(C 0~3The heterocycloalkyl group in (alkylene)-heterocycloalkyl is each optionally substituted with one or more groups R Cyc and any two groups R Y (if present) that are attached to the same ring carbon atom may also (i) join together and, together with the carbon atom to which they are attached, form a cycloalkyl (e.g., C 3~7 cycloalkyl) or heterocycloalkyl (e.g., 3- to 7-membered heterocycloalkyl), said cycloalkyl or said heterocycloalkyl being optionally substituted with one or more groups R Cyc or (ii) form a group =O with each other. More preferably, each R Y is independently selected from C 1~5 alkyl, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN. Ring B is substituted with 0, 1, 2, or 3 groups R Y , more preferably 0, 1, or 2 groups R Y , even more preferably 0 or 1 group R Y , and even more preferably, ring B is not substituted with any group R Y .

[0132] Group L is selected from -CO-, -SO-, and -SO2-. Preferably, L is -CO- or -SO2-. More preferably, L is -CO-. Group A is -N(-R N )-R N or heterocyclyl, said heterocyclyl being attached to group L via a ring nitrogen atom, said heterocyclyl being optionally substituted with one or more (e.g., 1, 2, 3, or 4) groups R A .

[0133] Each R N is hydrogen, C 1~8 alkyl, C 2~8 alkenyl, C 2~8 alkynyl, -(C 0~8 alkylene)-OH, -(C 0~8 alkylene)-O(C 1~5 alkyl), -(C 0~8 alkylene)-SH, -(C 0~8 alkylene)-S(C 1~5 alkyl), -(C 1~8 alkylene)-NH2, -(C 1~8 alkylene)-NH(C 1~5 alkyl), -(C 1~8 alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 1~8 alkylene)-halogen, -(C 1~8 alkylene)-C 1~5 haloalkyl, -(C 0~8 alkylene)-O-(C 1~8 haloalkyl), -(C 0~8 alkylene)-CN, -(C 0~8 alkylene)-CHO, -(C 0~8 alkylene)-CO-(C 1~5 alkyl), -(C 0~8 alkylene)-COOH, -(C 0~8 alkylene)-CO-O-(C 1~5 alkyl), -(C 0~8 alkylene)-O-CO-(C 1~5 alkyl), -(C 0~8 alkylene)-CO-NH2, -(C 0~8 alkylene)-CO-NH(C 1~5 alkyl), -(C 0~8 alkylene)-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 1~8 alkylene)-NH-CO-(C 1~5 alkyl), -(C 1~8 alkylene)-N(C 1~5 alkyl)-CO-(C 1~5 alkyl), -(C1~8 (alkylene)-NH-COO(C 1~5 alkyl), -(C 1~8 (alkylene)-N(C 1~5 alkyl)-COO(C 1~5 alkyl), -(C 0~8 (alkylene)-O-CO-NH(C 1~5 alkyl), -(C 0~8 (alkylene)-O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~8 (alkylene)-SO2-NH2, -(C 0~8 (alkylene)-SO2-NH(C 1~5 alkyl), -(C 0~8 (alkylene)-SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 1~8 (alkylene)-NH-SO2-(C 1~5 alkyl), -(C 1~8 (alkylene)-N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -(C 0~8 (alkylene)-SO-(C 1~5 alkyl), -(C 0~8 (alkylene)-SO2-(C 1~5 alkyl), -(C 0~8 (alkylene)-carbocyclic, and -(C 0~8 (alkylene)-heterocyclic, independently selected from, said C 1~8 alkyl, said C 2~8 alkenyl, said C 2~8 alkynyl, and said foregoing C 0~8 alkylene and C 1~8 any one or more (e.g., 1, 2, or 3) of the -CH2- units contained in either of the alkylene and C 1~5 alkylene groups may each be replaced by a group independently selected from -O-, -NH-, -N(C 0~8 alkyl)-, -CO-, -S-, -SO-, and -SO2-, said -(C 0~8The heterocyclic group in (alkylene)-heterocyclyl may each be substituted with one or more (e.g., 1, 2, or 3) groups R Cyc and at least one group R N is not hydrogen.

[0134] Preferably, each R N is hydrogen, C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~5 alkylene)-OH, -(C 0~5 alkylene)-O(C 1~5 alkyl), -(C 0~5 alkylene)-SH, -(C 0~5 alkylene)-S(C 1~5 alkyl), -(C 1~5 alkylene)-NH2, -(C 1~5 alkylene)-NH(C 1~5 alkyl), -(C 1~5 alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 1~5 alkylene)-halogen, -(C 1~5 alkylene)-C 1~5 haloalkyl, -(C 0~5 alkylene)-O-(C 1~5 haloalkyl), -(C 0~5 alkylene)-CN, -(C 0~5 alkylene)-CHO, -(C 0~5 alkylene)-CO-(C 1~5 alkyl), -(C 0~5 alkylene)-COOH, -(C 0~5 alkylene)-CO-O-(C 1~5 alkyl), -(C 0~5 alkylene)-O-CO-(C 1~5 alkyl), -(C 0~5 alkylene)-CO-NH2, -(C 0~5 alkylene)-CO-NH(C 1~5 alkyl), -(C 0~5 alkylene)-CO-N(C 1~5 alkyl)(C 1~5alkyl), -(C 1~5 alkylene)-NH-CO-(C 1~5 alkyl), -(C 1~5 Alkylene)-N(C 1~5 Alkyl)-CO-(C 1~5 alkyl), -(C 1~5 alkylene)-NH-COO(C 1~5 alkyl), -(C 1~5 Alkylene)-N(C 1~5 Alkyl)-COO(C 1~5 alkyl), -(C 0~5 alkylene)-O-CO-NH(C 1~5 alkyl), -(C 0~5 alkylene)-O-CO-N(C 1~5 Alkyl)(C 1~5 alkyl), -(C 0~5 alkylene)-SO2-NH2, -(C 0~5 alkylene)-SO2-NH(C 1~5 alkyl), -(C 0~5 Alkylene)-SO2-N(C 1~5 Alkyl)(C 1~5 alkyl), -(C 1~5 alkylene)-NH-SO2-(C 1~5 alkyl), -(C 1~5 Alkylene)-N(C 1~5 Alkyl)-SO2-(C 1~5 alkyl), -(C 0~5 alkylene)-SO-(C 1~5 alkyl), -(C 0~5 Alkylene)-SO2-(C 1~5 alkyl), -(C 0~5 alkylene)-carbocyclyl, and -(C 0~5 alkylene)-heterocyclyl, 1~5 Alkyl, the C 2~5 Alkenyl, 2~5 Alkynyl, as well as the aforementioned C 0~5 Alkylene and C 1~5 One or more (e.g., 1, 2, or 3) -CH2- units in any of the alkylene groups can each be selected from -O-, -NH-, -N(C 1~5may be replaced by a group independently selected from alkyl)-, -CO-, -S-, -SO-, and -SO2-, and said -(C 0~5 The carbocyclic group in the -(alkylene)-carbocyclic group and the -(C 0~5 The heterocyclic group in the -(alkylene)-heterocyclic group may each be substituted with one or more (e.g., 1, 2, or 3) groups R Cyc and at least one group R N is not hydrogen.

[0135] As described above, when the group A is -N(-R N )-R N at least one group R N is not hydrogen. In particular, the group A may be, for example, -NH-R N , -N(C 1~5 alkyl)-R N , or -N[-(C 1~5 alkylene)-O(C 1~5 alkyl)]-R N wherein R N is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~5 alkylene)-OH, -(C 0~5 alkylene)-O(C 1~5 alkyl), -(C 0~5 alkylene)-SH, -(C 0~5 alkylene)-S(C 1~5 alkyl), -(C 1~5 alkylene)-NH2, -(C 1~5 alkylene)-NH(C 1~5 alkyl), -(C 1~5 alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 1~5 alkylene)-halogen, -(C 1~5 alkylene)-C 1~5 haloalkyl, -(C 0~5 alkylene)-O-(C 1~5 haloalkyl), -(C 0~5(Alkylene)-CN, -(C 0~5 (Alkylene)-CHO, -(C 0~5 (Alkylene)-CO-(C 1~5 (Alkyl), -(C 0~5 (Alkylene)-COOH, -(C 0~5 (Alkylene)-CO-O-(C 1~5 (Alkyl), -(C 0~5 (Alkylene)-O-CO-(C 1~5 (Alkyl), -(C 0~5 (Alkylene)-CO-NH2, -(C 0~5 (Alkylene)-CO-NH(C 1~5 (Alkyl), -(C 0~5 (Alkylene)-CO-N(C 1~5 (Alkyl)(C 1~5 (Alkyl), -(C 1~5 (Alkylene)-NH-CO-(C 1~5 (Alkyl), -(C 1~5 (Alkylene)-N(C 1~5 (Alkyl)-CO-(C 1~5 (Alkyl), -(C 1~5 (Alkylene)-NH-COO(C 1~5 (Alkyl), -(C 1~5 (Alkylene)-N(C 1~5 (Alkyl)-COO(C 1~5 (Alkyl), -(C 0~5 (Alkylene)-O-CO-NH(C 1~5 (Alkyl), -(C 0~5 (Alkylene)-O-CO-N(C 1~5 (Alkyl)(C 1~5 (Alkyl), -(C 0~5 (Alkylene)-SO2-NH2, -(C 0~5 (Alkylene)-SO2-NH(C 1~5 (Alkyl), -(C 0~5 (Alkylene)-SO2-N(C 1~5 (Alkyl)(C 1~5 (Alkyl), -(C 1~5 (Alkylene)-NH-SO2-(C 1~5 (Alkyl), -(C 1~5 (Alkylene)-N(C 1~5 (Alkyl)-SO2-(C 1~5 (Alkyl), -(C 0~5(alkylene)-SO-(C 1~5 alkyl), -(C 0~5 (alkylene)-SO2-(C 1~5 alkyl), -(C 0~5 (alkylene)-carbocyclyl, and -(C 0~5 (alkylene)-heterocyclyl, and the C 1~5 alkyl, the C 2~5 alkenyl, the C 2~5 alkynyl, and the aforementioned C 0~5 alkylene and C 1~5 One or more (e.g., 1, 2, or 3) -CH2- units contained in any of the alkylene and C 1~5 alkylene groups may each be replaced by a group independently selected from -O-, -NH-, -N(C 0~5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, the carbocyclyl group in the -(C 0~5 alkylene)-carbocyclyl and the heterocyclyl group in the -(C Cyc alkylene)-heterocyclyl may each be substituted by one or more (e.g., 1, 2, or 3) groups R Cyc . Corresponding preferred examples of group A are -NH-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-4,6-dimethyl-pyridin-2-yl), -NH-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-pyridin-2-yl), -NH-C(-CH3)(-CH3)-CO-N(-CH3)-CH2-CO-NH2, -NH-C(-CH3)(-CH3)-CO-N(-CH3)(-CH3), -NH-C(-CH3)(-CH3)-CO-NH-CH3, -NH-CH(-CH3)-CH2-COOH, -NH-CH2-CH2-CH(-CH3)-COOH, -NH-CH2-CH2-CH(-CH3)-CH2-COOH, -NH-CH2-CH2-CH(-CH3)-CH2-CO-NH2, -NH-CH2-CH2-CH(-CH3)-CH2-CO-N(-CH3)-CH3, -NH-(1-(aminocarbonyl)cyclopropan-1-yl), -N(C 1~5(alkyl)-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-4,6-dimethyl-pyridin-2-yl), -N(C 1~5 (alkyl)-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-pyridin-2-yl), -N(C 1~5 (alkyl)-C(-CH3)(-CH3)-CO-N(-CH3)-CH2-CO-NH2, -N(C 1~5 (alkyl)-C(-CH3)(-CH3)-CO-N(-CH3)(-CH3), -N(C 1~5 (alkyl)-C(-CH3)(-CH3)-CO-NH-CH3, -N(C 1~5 (alkyl)-CH(-CH3)-CH2-COOH, -N(C 1~5 (alkyl)-CH2-CH2-CH(-CH3)-COOH, -N(C 1~5 (alkyl)-CH2-CH2-CH(-CH3)-CH2-COOH, -N(C 1~5 (alkyl)-CH2-CH2-CH(-CH3)-CH2-CO-NH2, -N(C 1~5 (alkyl)-CH2-CH2-CH(-CH3)-CH2-CO-N(-CH3)-CH3, -N(C 1~5 (alkyl)-(1-(aminocarbonyl)cyclopropan-1-yl), -N[-(C 1~5 (alkylene)-O(C 1~5 (alkyl)]-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-4,6-dimethyl-pyridin-2-yl), -N[-(C 1~5 (alkylene)-O(C 1~5 (alkyl)]-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-pyridin-2-yl), -N[-(C 1~5 (alkylene)-O(C 1~5 (alkyl)]-C(-CH3)(-CH3)-CO-N(-CH3)-CH2-CO-NH2, -N[-(C 1~5 (alkylene)-O(C 1~5 (alkyl)]-C(-CH3)(-CH3)-CO-N(-CH3)(-CH3), -N[-(C 1~5 (alkylene)-O(C 1~5alkyl)]-C(-CH3)(-CH3)-CO-NH-CH3, -N[-(C 1~5 alkylene)-O(C 1~5 alkyl)]-CH(-CH3)-CH2-COOH, -N[-(C 1~5 alkylene)-O(C 1~5 alkyl)]-CH2-CH2-CH(-CH3)-COOH, -N[-(C 1~5 alkylene)-O(C 1~5 alkyl)]-CH2-CH2-CH(-CH3)-CH2-COOH, -N[-(C 1~5 alkylene)-O(C 1~5 alkyl)]-CH2-CH2-CH(-CH3)-CH2-CO-NH2, -N[-(C 1~5 alkylene)-O(C 1~5 alkyl)]-CH2-CH2-CH(-CH3)-CH2-CO-N(-CH3)-CH3, or -N[-(C 1~5 alkylene)-O(C 1~5 alkyl)]-(1-(aminocarbonyl)cyclopropan-1-yl). Particularly preferred examples of group A are -N(-CH3)-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-4,6-dimethyl-pyridin-2-yl), -N(-CH3)-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-pyridin-2-yl), -N(-CH2CH2-O-CH3)-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-4,6-dimethyl-pyridin-2-yl), -N(-CH2CH2-O-CH3)-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxy-pyridin-2-yl), -N(-CH3)-C(-CH3)(-CH3)-CO-N(-CH3)-CH2-CO-NH2, -N(-CH3)-C(-CH3)(-CH3)-CO-N(-CH3)(-CH3), -N(-CH3)-C(-CH3)(-CH3)-CO-NH-CH3, -N(-CH3)-CH(-CH3)-CH2-COOH, -N(-CH3)-CH2-CH2-CH(-CH3)-COOH, -N(-CH3)-CH2-CH2-CH(-CH3)-CH2-COOH, -N(-CH3)-CH2- It contains CH2-CH(-CH3)-CH2-CO-NH2, -N(-CH3)-CH2-CH2-CH(-CH3)-CH2-CO-N(-CH3)-CH3, or -NH-(1-(aminocarbonyl)cyclopropan-1-yl).

[0136] Preferably, group A is a heterocyclyl bonded to group L via a ring nitrogen atom, and the heterocyclyl may be substituted with one or more groups R A The heterocyclyl may be, for example, a 5- to 14-membered heterocyclyl. More preferably, group A is a heterocycloalkyl or a heterocycloalkenyl, the heterocycloalkyl or the heterocycloalkenyl is bonded to group L via a ring nitrogen atom, and the heterocycloalkyl or the heterocycloalkenyl may be substituted with one or more groups R A The heterocycloalkyl or the heterocycloalkenyl may be, for example, a 5- to 14-membered heterocycloalkyl or a 5- to 14-membered heterocycloalkenyl. Even more preferably, group A is a heterocycloalkyl bonded to group L via a ring nitrogen atom, and the heterocycloalkyl may be substituted with one or more groups R AIt may be replaced by. The heterocycloalkyl preferably contains one nitrogen ring atom (through which the heterocycloalkyl is bonded to group L), and may contain one or more (e.g., 1, 2, or 3) additional ring heteroatoms independently selected from nitrogen, oxygen, and sulfur, and is a 5- to 11-membered heterocycloalkyl in which all the remaining ring atoms are carbon atoms. Any nitrogen ring atom (if present) and / or any sulfur ring atom (if present) may be oxidized, and one or more carbon ring atoms may be oxidized (i.e., to form an oxo group). More preferably, the heterocycloalkyl contains one nitrogen ring atom (through which the heterocycloalkyl is bonded to group L), and may contain 1 or 2 additional ring heteroatoms independently selected from nitrogen, oxygen, and sulfur, and is a 5- to 7-membered (even more preferably 6-membered) monocyclic heterocycloalkyl in which all the remaining ring atoms are carbon atoms. Any nitrogen ring atom (if present) and / or any sulfur ring atom (if present) may be oxidized, and one or more carbon ring atoms may be oxidized. Further, the heterocycloalkyl may contain a lactam functional group, i.e., the heterocycloalkyl may contain a second nitrogen ring atom adjacent to the oxidized carbon ring atom (C=O) (in addition to the first nitrogen ring atom through which group A is bonded to group L). Corresponding preferred examples of group A are one or more (e.g., 1, 2, 3, or 4) groups R A which may be substituted with 3-oxopiperazin-1-yl. A particularly preferred corresponding example of group A is 2,2-dimethyl-piperazin-3-one-1-yl (one or more R A which may be further substituted with). Further preferred examples of group A are one or more (e.g., 1, 2, 3, or 4) groups R AIt may be replaced by 4-(5-carboxypyridin-2-yl)piperazin-1-yl, and corresponding preferred examples of group A are 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl or 2,2-dimethyl-4-(5-carboxy-pyridin-2-yl)piperazin-1-yl (each with one or more R A which may be further substituted), particularly including 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl. Further preferred examples of group A are 4-(5-carboxymethylpyridin-2-yl)piperazin-1-yl which may be substituted with one or more (e.g., 1, 2, 3, or 4) groups R A and corresponding preferred examples of group A include 2,2-dimethyl-4-(5-carboxymethylpyridin-2-yl)piperazin-1-yl (which may be further substituted with one or more R A ). Further preferred examples of group A are each 4-(4-carboxythiazol-2-yl)piperazin-1-yl or 4-(5-carboxythiazol-2-yl)piperazin-1-yl which may be substituted with one or more (e.g., 1, 2, 3, or 4) groups R A and corresponding preferred examples of group A include 2,2-dimethyl-4-(4-carboxythiazol-2-yl)piperazin-1-yl or 2,2-dimethyl-4-(5-carboxythiazol-2-yl)piperazin-1-yl (each with one or more R A which may be further substituted). Further preferred examples of group A are 4-(carboxymethyl)piperidin-1-yl which may be substituted with one or more (e.g., 1, 2, 3, or 4) groups R A and corresponding preferred examples of group A include 3-methoxy-4-(carboxymethyl)piperidin-1-yl, 3-methyl-4-(carboxymethyl)piperidin-1-yl, or 3-fluoro-4-(carboxymethyl)piperidin-1-yl (each with one or more R A which may be further substituted).

[0137] Further examples of group A include any of the specific groups A included in the compounds of formula (I) described in the Examples section, particularly any one of Examples 1 to 282. Each R A is 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -(C 0~3 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-O(C 1~5 alkylene)-OH, -(C 0~3 alkylene)-O(C 1~5 alkylene)-O(C 1~5 alkyl), -(C 0~3 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-S(C 1~5 alkylene)-SH, -(C 0~3 alkylene)-S(C 1~5 alkylene)-S(C 1~5 alkyl), -(C 0~3 alkylene)-NH2, -(C 0~3 alkylene)-NH(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 alkylene)-NH-OH, -(C 0~3 alkylene)-N(C 1~5 alkyl)-OH, -(C 0~3 alkylene)-NH-O(C 1~5 alkyl), -(C 0~3 alkylene)-N(C 1~5 alkyl)-O(C 1~5 alkyl), -(C 0~3 alkylene)-halogen, -(C 0~3 alkylene)-(C 1~5 haloalkyl), -(C 0~3 alkylene)-O-(C 1~5 haloalkyl), -(C0~3 -(alkylene)-CN, -(C 0~3 -(alkylene)-CHO, -(C 0~3 -(alkylene)-CO-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-COOH, -(C 0~3 -(alkylene)-CO-O-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-O-CO-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-CO-NH2, -(C 0~3 -(alkylene)-CO-NH(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-CO-N(C 1~5 -(alkyl)(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-NH-CO-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-N(C 1~5 -(alkyl)-CO-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-NH-COO(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-N(C 1~5 -(alkyl)-COO(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-O-CO-NH(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-O-CO-N(C 1~5 -(alkyl)(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-SO2-NH2, -(C 0~3 -(alkylene)-SO2-NH(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-SO2-N(C 1~5 -(alkyl)(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-NH-SO2-(C 1~5 -(alkyl), -(C 0~3 -(alkylene)-N(C 1~5 -(alkyl)-SO2-(C 1~5 -(alkyl), -(C0~3 -(alkylene)-SO-(C 1~5 alkyl), -(C 0~3 -(alkylene)-SO2-(C 1~5 alkyl), -(C 0~3 -(alkylene)-carbocyclyl, -(C 0~3 -(alkylene)-heterocyclyl, and -L Z -R Z independently selected from, said -(C 0~3 The carbocyclyl group in -alkylene)-carbocyclyl and the heterocyclyl group in said -(C 0~3 -alkylene)-heterocyclyl may each be substituted with one or more (e.g., 1, 2, or 3) groups R Cyc and further, any two groups R A bonded to the same carbon atom of group A may also be joined to each other to form, together with the carbon atom to which they are bonded, a cycloalkyl or heterocycloalkyl, said cycloalkyl or said heterocycloalkyl may be substituted with one or more (e.g., 1, 2, or 3) groups R Cyc .

[0138] Preferably, each R A is C 1~5 alkyl, -(C 0~3 -alkylene)-OH, -(C 0~3 -alkylene)-O(C 1~5 alkyl), -(C 0~3 -alkylene)-SH, -(C 0~3 -alkylene)-S(C 1~5 alkyl), -(C 0~3 -alkylene)-NH2, -(C 0~3 -alkylene)-NH(C 1~5 alkyl), -(C 0~3 -alkylene)-N(C 1~5 alkyl)(C 1~5 alkyl), -(C 0~3 -alkylene)-halogen, -(C 0~3 -alkylene)-(C 1~5 haloalkyl), -(C 0~3 -alkylene)-O-(C 1~5-(Haloalkyl), -(C 0~3 -Alkylene)-CN, -(C 0~3 -Alkylene)-CHO, -(C 0~3 -Alkylene)-CO-(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-COOH, -(C 0~3 -Alkylene)-CO-O-(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-O-CO-(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-CO-NH2, -(C 0~3 -Alkylene)-CO-NH(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-CO-N(C 1~5 -Alkyl)(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-NH-CO-(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-N(C 1~5 -Alkyl)-CO-(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-NH-COO(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-N(C 1~5 -Alkyl)-COO(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-O-CO-NH(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-O-CO-N(C 1~5 -Alkyl)(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-SO2-NH2, -(C 0~3 -Alkylene)-SO2-NH(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-SO2-N(C 1~5 -Alkyl)(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-NH-SO2-(C 1~5 -Alkyl), -(C 0~3 -Alkylene)-N(C 1~5 -Alkyl)-SO2-(C1~5 alkyl), -(C 0~3 alkylene)-aryl, -(C 0~3 alkylene)-cycloalkyl (e.g., cyclopropyl), -(C 0~3 alkylene)-heteroaryl (e.g., pyridinyl; e.g., pyridin-2-yl), and -(C 0~3 alkylene)-heterocycloalkyl, independently selected, wherein the -(C 0~3 aryl group in the alkylene)-aryl, the -(C 0~3 cycloalkyl group in the alkylene)-cycloalkyl, the -(C 0~3 heteroaryl group in the alkylene)-heteroaryl, and the -(C 0~3 heterocycloalkyl group in the alkylene)-heterocycloalkyl may each be substituted with one or more groups R Cyc and, any two groups R bonded to the same carbon atom of group A A may also be joined to each other to form, together with the carbon atom to which they are attached, cycloalkyl (e.g., C 3~7 cycloalkyl, e.g., cyclopropyl).

[0139] When group A is heterocyclyl (as described above herein and including any of the corresponding preferred or exemplary cyclic group A described herein; hereinafter referred to as "ring A"), at least two substituents R A are present, which are bonded to the same carbocyclic atom of ring A and each independently is a C 1~5 alkyl group or joined to each other to form, together with the carbocyclic atom to which they are attached, a C 3~7 cycloalkyl group, which is particularly preferred. Thus, group A is a heterocycloalkyl (including any of the specific heterocycloalkyl groups described above herein) bonded to group L via a ring nitrogen atom, and the heterocycloalkyl has (i) two C 1~5substituted with an alkyl group or (ii) bonded to the same ring carbon atom and joined to each other to form, together with the ring carbon atom to which they are bonded, a C 3~7 substituents R that together form a cycloalkyl group (e.g., a cyclopropyl group) A and the heterocycloalkyl is substituted with one or more groups R A is particularly preferably further substituted. Even more preferably, group A is a heterocycloalkyl (including any of the specific heterocycloalkyl groups described above herein) bonded to group L via a ring nitrogen atom, and the heterocycloalkyl has two C 1~5 alkyl groups bonded to the same ring carbon atom, and the heterocycloalkyl may be further substituted with one or more groups R A (e.g., with one group R which is 5-carboxy-4,6-dimethyl-pyridin-2-yl) A (and) is further substituted. The two C 1~5 alkyl groups bonded to the same ring carbon atom may be the same or different and are preferably independently selected from methyl, ethyl, propyl and butyl, and more preferably the two C 1~5 alkyl groups bonded to the same ring carbon atom are each methyl. C 3~7 The cycloalkyl group (formed from two joined substituents R A ) is preferably selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, and more preferably the C 3~7 cycloalkyl group is a cyclopropyl group. The two C 1~5 alkyl groups or the two joined substituents R A (which together form a C 3~7 cycloalkyl group) are bonded at a position, i.e., a specific carbocyclic atom of ring A, which is not particularly limited. For example, the two C 1~5 alkyl groups or the two joined substituents R A (which together form a C 3~7(which forms a cycloalkyl group) may be bonded to a carbon ring atom (of ring A) that is (i) directly adjacent to the nitrogen ring atom through which ring A is bonded to group L, or (ii) separated from said nitrogen ring atom (through which ring A is bonded to group L) by one ring atom, or (iii) separated from said nitrogen ring atom (through which ring A is bonded to group L) by two ring atoms. Corresponding preferred examples of ring A include 2,2-dimethyl-piperazin-1-yl, 3,3-dimethyl-piperazin-1-yl, 2,2-dimethyl-piperazin-3-one-1-yl, 2,2,4-trimethyl-piperazin-3-one-1-yl, 4-ethyl-2,2-dimethyl-piperazin-3-one-1-yl, spiro[piperazine-2,1'-cyclopropane]-1-yl, spiro[piperazine-3,1'-cyclopropane]-1-yl, 2,2-dimethyl-piperidin-1-yl, 3,3-dimethyl-piperidin-1-yl, 4,4-dimethyl-piperidin-1-yl, spiro[piperidine-2,1'-cyclopropane]-1-yl, spiro[piperidine-3,1'-cyclopropane]-1-yl, or spiro[piperidine-4,1'-cyclopropane]-1-yl, and the piperazinyl moiety, piperazinonyl moiety or piperidinyl moiety in each of the aforementioned groups may be substituted with one or more (e.g., 1 or 2) groups R A (e.g., one group R selected from 5-carboxypyridin-2-yl, 5-carboxy-4,6-dimethyl-pyridin-2-yl, 5-carboxymethyl-pyridin-2-yl, 5-carboxymethyl-4,6-dimethyl-pyridin-2-yl, 4-carboxythiazol-2-yl, and 5-carboxythiazol-2-yl) A and may be further substituted. Two C 1~5 alkyl groups or two substituents R bonded to each other A (together forming a C 3~7The (cycloalkyl group, preferably a cyclopropyl group) is particularly preferably bonded to a carbocyclic atom directly adjacent to the nitrogen ring atom through which ring A is bonded to group L. A particularly preferred example of ring A is 2,2-dimethyl-piperazin-1-yl, and the piperazinyl group in the 2,2-dimethyl-piperazin-1-yl may be further substituted with one or more groups R A and thus, ring A may be, for example, 2,2-dimethyl-4-(5-carboxypyridin-2-yl)piperazin-1-yl, 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl, 2,2-dimethyl-4-(5-carboxymethylpyridin-2-yl)piperazin-1-yl, 2,2-dimethyl-4-(5-carboxymethyl-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl, 2,2-dimethyl-4-(4-carboxythiazol-2-yl)piperazin-1-yl, or 2,2-dimethyl-4-(5-carboxythiazol-2-yl)piperazin-1-yl. An even more preferred example of ring A is 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl.

[0140] According to the above, group A is one of the following groups:

[0141]

Chemical formula

[0142] It is particularly preferred to be selected from any one of them. A particularly preferred example of group A is 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl:

[0143]

Chemical formula

[0144] That is. The present invention particularly relates to compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein group A is 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl, and R 2A and R 2B are joined to each other and together with the carbon atom to which they are attached form a C 21 cycloalkyl (preferably cyclopentyl) which may be substituted with one or more groups R 3~7 . The present invention also particularly relates to compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein group A is 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl, and R 2A and R 2B are each independently C 1~5 alkyl (for example, R 2A and R 2B may each be methyl).

[0145] A further particularly preferred example of group A is 3-methoxy-4-(carboxymethyl)piperidin-1-yl:

[0146]

Chemical formula

[0147] which is as follows. The present invention particularly relates to compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein group A is 3-methoxy-4-(carboxymethyl)piperidin-1-yl, and R 2A and R 2B are each independently C 1~5 alkyl (for example, R 2A and R 2B may each be methyl).

[0148] A further particularly preferred example of group A is 2,2-dimethyl-3-oxo-piperazin-1-yl:

[0149] [Chemical formula]

[0150] is as follows. The present invention particularly relates to a compound of formula (I) wherein group A is 2,2-dimethyl-3-oxo-piperazin-1-yl, and R 2A and R 2B are each independently C 1~5 alkyl (for example, R 2A and R 2B may each be methyl), and its pharmaceutically acceptable salts and solvates.

[0151] Each R Cyc is C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -NH-OH, -N(C 1~5 alkyl)-OH, -NH-O(C 1~5 alkyl), -N(C 1~5 alkyl)-O(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO(C 1~5 alkyl), -COOH, -COO(C 1~5 alkyl), -O-CO(C 1~5 alkyl), -CO-NH2, -CO-NH(C 1~5 alkyl), -CO-N(C 1~5(alkyl)(C 1~5 alkyl), -NH-CO(C 1~5 alkyl), -N(C 1~5 alkyl)-CO(C 1~5 alkyl), -NH-COO(C 1~5 alkyl), -N(C 1~5 alkyl)-COO(C 1~5 alkyl), -O-CO-NH(C 1~5 alkyl), -O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -SO2-NH2, -SO2-NH(C 1~5 alkyl), -SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-SO2-(C 1~5 alkyl), -N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -SO2-(C 1~5 alkyl), -SO-(C 1~5 alkyl), -P(=O)(-OH)(-OH), -P(=O)(-OH)(-O-C 1~5 alkyl), -P(=O)(-O-C 1~5 alkyl)(-O-C 1~5 alkyl), -(C 0~3 alkylene)-cycloalkyl, -(C 0~3 alkylene)-heterocycloalkyl, and -L Z -R Z is independently selected from.

[0152] Preferably, each R Cyc is, C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5(alkyl), -NH2, -NH(C 1~5 (alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-OH, -N(C 1~5 (alkyl)-OH, -NH-O(C 1~5 (alkyl), -N(C 1~5 (alkyl)-O(C 1~5 (alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO(C 1~5 (alkyl), -COOH, -COO(C 1~5 (alkyl), -O-CO(C 1~5 (alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-CO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO(C 1~5 (alkyl), -NH-COO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), -(C 0~3 (alkylene)-cycloalkyl, -(C 0~3 (alkylene)-heterocycloalkyl, and -L Z -R Z is independently selected from. More preferably, each R Cyc is, C 1~5Alkyl, -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), and -CN are independently selected.

[0153] Each L Z is independently selected from a covalent bond, C 1~7 alkylene, C 2~7 alkenylene, and C 2~7 alkynylene, wherein the alkylene, the alkenylene, and the alkynylene are each substituted with one or more (e.g., 1, 2, or 3) groups independently selected from halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), and -N(C 1~5 alkyl)(C 1~5 alkyl), and furthermore, one or more (e.g., 1, 2, or 3) -CH2- units contained in the alkylene, the alkenylene, or the alkynylene may each be replaced by a group independently selected from -O-, -NH-, -N(C 1~5 alkyl)-, -CO-, -S-, -SO-, and -SO2-.

[0154] Preferably, each L Z is a covalent bond, C 1~5 alkylene, C 2~5 alkenylene, and C 2~5Independently selected from alkynylene, and said alkylene, said alkenylene and said alkynylene are each halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), and -N(C 1~5 alkyl)(C 1~5 alkyl) and may be substituted with one or more (e.g., 1, 2, or 3) groups independently selected from, and further, one or more (e.g., 1, 2, or 3) -CH2- units contained in said alkylene, said alkenylene or said alkynylene may each be replaced by a group independently selected from -O-, -NH-, -N(C 1~5 alkyl)-, -CO-, -S-, -SO-, and -SO2-.

[0155] Each R Z is -OH, -O(C 1~5 alkyl), -O(C 1~5 alkylene)-OH, -O(C 1~5 alkylene)-O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -S(C 1~5 alkylene)-SH, -S(C 1~5 alkylene)-S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), -N(C 1~5 alkyl)(C 1~5 alkyl), -NH-OH, -N(C 1~5 alkyl)-OH, -NH-O(C 1~5 alkyl), -N(C 1~5 alkyl)-O(C 1~5 alkyl), halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO(C 1~5 alkyl), -COOH, -COO(C 1~5 alkyl), -O-CO(C 1~5(alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-CO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO(C 1~5 (alkyl), -NH-COO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, independently selected, wherein said aryl, said heteroaryl, said cycloalkyl, and said heterocycloalkyl are each, C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -OH, -O(C 1~5 (alkyl), -SH, -S(C 1~5 (alkyl), -NH2, -NH(C 1~5 (alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), -CHO, -CO-(C 1~5 (alkyl), -COOH, -CO-O-(C 1~5 (alkyl), -O-CO-(C 1~5 (alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C(alkyl) 1~5(alkyl)(C 1~5 (alkyl), -NH-CO-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-CO-(C 1~5 (alkyl), -NH-COO(C 1~5 (alkyl), -N(C 1~5 (alkyl)-COO(C 1~5 (alkyl), -O-CO-NH(C 1~5 (alkyl), -O-CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -SO2-NH2, -SO2-NH(C 1~5 (alkyl), -SO2-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-SO2-(C 1~5 (alkyl), -N(C 1~5 (alkyl)-SO2-(C 1~5 (alkyl), -SO-(C 1~5 (alkyl), -SO2-(C 1~5 (alkyl), and may be substituted with one or more (e.g., 1, 2, or 3) groups independently selected from carbocyclic and heterocyclic, wherein said carbocyclic and said heterocyclic are each C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 (alkyl), -N(C 1~5 (alkyl)(C 1~5 (alkyl), -CHO, -CO-(C 1~5 (alkyl), -COOH, -CO-O-(C 1~5 (alkyl), -O-CO-(C 1~5 (alkyl), -CO-NH2, -CO-NH(C 1~5 (alkyl), -CO-N(C 1~5 (alkyl)(C 1~5 (alkyl), -NH-CO-(C 1~5 (alkyl), -N(C1~5 -CO-(C(alkyl)) 1~5 -NH-COO(C(alkyl)) 1~5 -N(C(alkyl)) 1~5 -COO(C(alkyl)) 1~5 -O-CO-NH(C(alkyl)) 1~5 -O-CO-N(C(alkyl)) 1~5 (C(alkyl)) 1~5 -SO2-NH2, -SO2-NH(C(alkyl)) 1~5 -SO2-N(C(alkyl)) 1~5 (C(alkyl)) 1~5 -NH-SO2-(C(alkyl)) 1~5 -N(C(alkyl)) 1~5 -N(C(alkyl))-SO2-(C(alkyl)) 1~5 -SO-(C(alkyl)) 1~5 -SO2-(C(alkyl)), and 1~5 optionally substituted with one or more groups independently selected from -SO2-(C(alkyl)).

[0156] Preferably, each R Z is -OH, -O(C(alkyl)), -O(C(alkylene))-OH, -O(C(alkylene))-O(C(alkyl)), -SH, -S(C(alkyl)), -S(C(alkylene))-SH, -S(C(alkylene))-S(C(alkyl)), -NH2, -NH(C(alkyl)), -N(C(alkyl))(C(alkyl)), -NH-OH, -N(C(alkyl))-OH, -NH-O(C(alkyl)), -N(C(alkyl))-O(C(alkyl)), halogen, C(haloalkyl), -O-(C(haloalkyl)), -CN, -CHO, -CO(C(alkyl)), -COOH, -COO(C(alkyl)), -O-CO(C(alkyl)) 1~5 -O(C(alkyl)) 1~5 -O(C(alkylene))-OH 1~5 -O(C(alkylene))-O(C(alkyl)) 1~5 -SH, -S(C(alkyl)) 1~5 -S(C(alkyl)) 1~5 -S(C(alkylene))-SH 1~5 -S(C(alkylene))-S(C(alkyl)) 1~5 -NH2, -NH(C(alkyl)) 1~5 -N(C(alkyl)) 1~5 (C(alkyl)) 1~5 -NH-OH, -N(C(alkyl))-OH 1~5 -NH-O(C(alkyl)) 1~5 -N(C(alkyl)) 1~5 -N(C(alkyl))-O(C(alkyl)) 1~5 halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -CHO, -CO(C 1~5 (alkyl)), -COOH, -COO(C 1~5 (alkyl)), -O-CO(C1~5 alkyl), -CO-NH2, -CO-NH(C 1~5 alkyl), -CO-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-CO(C 1~5 alkyl), -N(C 1~5 alkyl)-CO(C 1~5 alkyl), -NH-COO(C 1~5 alkyl), -N(C 1~5 alkyl)-COO(C 1~5 alkyl), -O-CO-NH(C 1~5 alkyl), -O-CO-N(C 1~5 alkyl)(C 1~5 alkyl), -SO2-NH2, -SO2-NH(C 1~5 alkyl), -SO2-N(C 1~5 alkyl)(C 1~5 alkyl), -NH-SO2-(C 1~5 alkyl), -N(C 1~5 alkyl)-SO2-(C 1~5 alkyl), -SO2-(C 1~5 alkyl), -SO-(C 1~5 alkyl), aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, independently selected, wherein said aryl, said heteroaryl, said cycloalkyl, and said heterocycloalkyl are each C 1~5 alkyl, C 2~5 alkenyl, C 2~5 alkynyl, halogen, C 1~5 haloalkyl, -O-(C 1~5 haloalkyl), -CN, -OH, -O(C 1~5 alkyl), -SH, -S(C 1~5 alkyl), -NH2, -NH(C 1~5 alkyl), and -N(C 1~5 alkyl)(C 1~5 alkyl) and may be substituted with one or more (e.g., 1, 2, or 3) groups independently selected from

[0157] It is preferred that at least one (more preferably all) of the following conditions apply to the compound of formula (I): - Ring B is a pyrrolidinyl ring, ring D is a pyridinyl ring, R 2A and R 2B are joined to each other and together with the carbon atom to which they are attached form a cyclopropyl, L is -CO-, and when group A is morpholin-4-yl, R 1 is not 5-R 11 -pyrimidin-2-yl or acetyl, and / or - Rings B and D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl ring, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-c]pyridinyl ring or 6-oxo-6,7-dihydro-5H-pyrrolo[2,3-c]pyridazinyl ring, R 2A and R 2B are each methyl, R 1 is phenyl which may be substituted with one or more groups R 11 and when L is -CO- and group A is -NH-R N R N is not a heterocycloalkyl which contains one oxidized sulfur ring atom and all other ring atoms are carbon atoms and is substituted with a methyl group, and / or - Rings B and D together form a 3-R X -4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring, R X is -OH, one of R 2A and R 2B is methyl, one of R 2A and R 2B is -CON(-CH3)2, R 1 is methyl, L is -CO- and when group A is -NH-R N R N is not 4-fluorobenzyl, and / or - Ring B and ring D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine ring, a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine ring or a 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine, L is -CO-, and the group A is -NH-R N wherein R 1 is -CH2-phenyl or -CH2-pyridinyl, and the phenyl in said -CH2-phenyl and the pyridinyl in said -CH2-pyridinyl are each optionally substituted with one or more groups R 11 wherein when so substituted, R 2A and R 2B are not methyl.

[0158] Therefore, as described above, it is preferable that the following conditions apply to the compound of formula (I): Ring B is a pyrrolidinyl ring, ring D is a pyridinyl ring, R 2A and R 2B are joined to each other to form a cyclopropyl together with the carbon atom to which they are attached, L is -CO-, and when the group A is morpholin-4-yl, R 1 is not 5-R 11 -pyrimidin-2-yl or acetyl. Therefore, when B is a pyrrolidinyl ring, D is a pyridinyl ring, R 2A and R 2B are joined to each other to form a cyclopropyl (together with the carbon atom to which they are attached), L is -CO-, and when the group A is morpholin-4-yl, it is preferable that the group R 1 is not 5-R 11 -pyrimidin-2-yl or acetyl (i.e., R 1 is not a pyrimidin-2-yl group having one substituent R 11 at the 5-position of the pyrimidine ring, and R 1 is not acetyl). More preferably, when ring B is a pyrrolidinyl ring, ring D is a pyridinyl ring, L is -CO-, and the group A is morpholin-4-yl, R 1 is not 5-R 11- is not pyrimidin-2-yl or acetyl. Even more preferably, when ring B is a pyrrolidinyl ring, ring D is a pyridinyl ring, and L is -CO-, R 1 is 5-R 11 - is not pyrimidin-2-yl or acetyl. Even more preferably, when ring B is a pyrrolidinyl ring and L is -CO-, R 1 is 5-R 11 - is not pyrimidin-2-yl or acetyl. Even more preferably, when ring B is a pyrrolidinyl ring, R 1 is 5-R 11 - is not pyrimidin-2-yl or acetyl. Even more preferably, R 1 is 5-R 11 - is not pyrimidin-2-yl (i.e., R 1 is a group different from 5-R 11 -pyrimidin-2-yl), and / or R 1 is not acetyl. Even more preferably, R 1 is 5-R 11 - is not pyrimidin-2-yl and is not acetyl.

[0159] Furthermore, as described above, the following conditions are preferably applied to the compound of formula (I): Rings B and D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl ring, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-c]pyridinyl ring or 6-oxo-6,7-dihydro-5H-pyrrolo[2,3-c]pyridazinyl ring, R 2A and R 2B are each methyl, R 1 is phenyl which may be substituted with one or more groups R 11 , L is -CO-, and when group A is -NH-R N is R Ncontains one oxidized sulfur ring atom, with all other ring atoms being carbon atoms and being substituted with methyl groups, and is not a heterocycloalkyl. Thus, ring B and ring D are fused to form a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl ring, a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-c]pyridinyl ring or a 6-oxo-6,7-dihydro-5H-pyrrolo[2,3-c]pyridazinyl ring, and R 2A and R 2B are each methyl, R 1 is phenyl which may be substituted with one or more groups R 11 , L is -CO-, the group A is -N(-R N )-R N , and when one group R N is hydrogen, the other group R N preferably contains one oxidized sulfur ring atom (especially the ring atom -S(=O)2-), with all other ring atoms being carbon atoms and being substituted with methyl groups, and is not a heterocycloalkyl. More preferably, ring B and ring D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl ring, a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-c]pyridinyl ring or a 6-oxo-6,7-dihydro-5H-pyrrolo[2,3-c]pyridazinyl ring, R 2A and R 2B are each methyl, L is -CO-, and when the group A is -NH-R N , R N contains one oxidized sulfur ring atom, with all other ring atoms being carbon atoms and being substituted with methyl groups, and is not a heterocycloalkyl. Even more preferably, ring B and ring D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl ring, a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-c]pyridinyl ring or a 6-oxo-6,7-dihydro-5H-pyrrolo[2,3-c]pyridazinyl ring, L is -CO-, and when the group A is -NH-R N , R NIt does not contain a heterocycloalkyl that contains one oxidized sulfur ring atom and all other ring atoms are carbon atoms and is substituted with a methyl group. Even more preferably, ring B is a 2-oxopyrrolidinyl ring, ring D is a pyridinyl ring or a pyridazinyl ring, L is -CO-, and group A is -NH-R N When it is N R N is a heterocycloalkyl that contains one oxidized sulfur ring atom and all other ring atoms are carbon atoms and is substituted with a methyl group. Even more preferably, ring B is a 2-oxopyrrolidinyl ring and group A is -NH-R N When it is N R N is a heterocycloalkyl that contains one oxidized sulfur ring atom and all other ring atoms are carbon atoms and is substituted with a methyl group. Even more preferably, group A is -NH-R N Rather than N R Cyc is a heterocycloalkyl that may be substituted with one or more groups R

[0160] Furthermore, as described above, the following conditions are preferably applied to the compound of formula (I): Rings B and D together form a 3-R X -4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl ring, R X is -OH, one of R 2A and R 2B is methyl, one of R 2A and R 2B is -CON(-CH3)2, R 1 is methyl, L is -CO-, and group A is -NH-R N When it is N R X is not 4-fluorobenzyl. Thus, rings B and D together form a single group R that is -OHis a 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring with the 3-position substituted, and R 2A and R 2B one of which is methyl, and R 2A and R 2B the other one of which is -CON(-CH3)CH3, R 1 is methyl, L is -CO-, and when the group A is -NH-R N , R N is not 4-fluorobenzyl (i.e., R N is not the group -CH2-(4-fluorophenyl)) is preferred. More preferably, when ring B and ring D together form a 3-R X -4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring and L is -CO-, R X is not -OH. Even more preferably, when ring D is a pyrazolyl ring which may be substituted with one or more groups R X , and L is -CO-, the one or more groups R X are not -OH.

[0161] Similarly as described above, the following conditions are preferably applied to the compound of formula (I): ring B and ring D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine ring, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine ring or 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine, L is -CO-, the group A is -NH-R N , and R 1 is -CH2-phenyl or -CH2-pyridinyl, and when the phenyl in the -CH2-phenyl and the pyridinyl in the -CH2-pyridinyl are each optionally substituted with one or more groups R 11 , R 2A and R 2Bis not methyl. More preferably, ring B and ring D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine ring, a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine ring or 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine, L is -CO-, and group A is -NH-R N when 2A and R 2B are not methyl. Even more preferably, ring B and ring D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine ring, a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine ring, 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine or 2-R Y -2,3-dihydro-1H-pyrrolo[2,3-b]pyridine ring, L is -CO-, and group A is -NH-R N when 2A and R 2B are not methyl. Still even more preferably, ring B is a 2-oxopyrrolidinyl ring or 2-R Y -pyrrolidinyl ring, ring D is a pyridinyl ring, L is -CO-, and group A is -NH-R N when 2A and R 2B are not methyl.

[0162] In addition to the above, the compound 1-(tert-butyl)-6-((4-fluorophenyl)carbamoyl)-2-oxo-1,2-dihydrospiro[pyrido[2,3-b][1,4]oxazine-3,3'-pyrrolidine] is preferably excluded from formula (I). More preferably, ring B is a non-aromatic 4- to 8-membered heterocyclic ring containing a -C(=O)-ring atom adjacent to the ring carbon atoms having R 2A and R 2B and said ring B may be substituted with one or more groups R Y and R 2A and R 2B are joined to each other and together with the carbon atom to which they are attached form one or more groups R 21When forming a pyrrolidin-3-yl group which may be replaced by, R 1 is not tert-butyl. Even more preferably, ring B is R 2A and R 2B is a non-aromatic 4- to 8-membered heterocyclic ring containing a -C(=O)-ring atom adjacent to the ring carbon atom having, and the ring B may be substituted with one or more groups R Y and when R 2A and R 2B are joined to each other and together with the carbon atom to which they are attached form a heterocycloalkyl which may be substituted with one or more groups R 21 , the heterocycloalkyl is not pyrrolidin-3-yl.

[0163] The compound of formula (I) is any one of the specific compounds of formula (I) described in the Examples section herein, in non-salt form and / or non-solvated form, or as a pharmaceutically acceptable salt or solvate of each compound, and particularly preferably includes any one of Examples 1 to 282 described below.

[0164] Thus, the compound of formula (I) is 1'-(4-chloro-3-fluorophenyl)-5'-(2,2-dimethyl-3-oxopiperazine-1-carbonyl)-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-2'(1'H)-one; 1'-(4-chloro-3-fluorophenyl)-5'-(2,2-dimethyl-3-oxopiperazine-1-carbonyl)spiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-2'(1'H)-one; 4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-2-one; 8-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclopentane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-1,3,8-triazaspiro[4.5]decan-2,4-dione; Methyl 1-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclopentane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperidine-4-carboxylate; 1-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclopentane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperidine-4-carboxylic acid; Methyl 6-(4-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclopentane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclopentane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 4-(1’-(3-chlorophenyl)-1’,2’-dihydrospiro[cyclopentane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-2-one; 4-(1’-(2-chlorophenyl)-1’,2’-dihydrospiro[cyclopentane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-2-one; 4-(3,3-dimethyl-1-(thiophen-3-yl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one; 4-(1-(3,4-difluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one; Methyl 6-(4-(1-(3,4-difluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(3,4-Difluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 4-(1-(4-Fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one; Methyl 6-(4-(1-(3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(3-Fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 4-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one; 4-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-1-ethyl-3,3-dimethylpiperazin-2-one; (1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-yl)(3,3-dimethylmorpholino)methanone; tert-Butyl 4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-carboxylate; (1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-5-yl)(2,2-dimethylpiperazin-1-yl)methanone; (1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-5-yl)(4-ethyl-2,2-dimethylpiperazin-1-yl)methanone; 1-(4-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)ethan-1-one; Ethyl 4-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-oxobutanoate; 4-(4-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-oxobutanoic acid; Ethyl 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-5-oxopentanoate; 5-(4-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-5-oxopentanoic acid; 8-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-1-methyl-1,3,8-triazaspiro[4.5]decan-4-one; 2-(3-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-azabicyclo[3.1.0]hexan-6-yl)acetic acid; Methyl 2-(3-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-azabicyclo[3.1.0]hexan-6-yl)acetate; Methyl 2-((1R,5S,6S)-3-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-azabicyclo[3.1.0]hexan-6-yl)acetate; 2-((1R,5S,6S)-3-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-azabicyclo[3.1.0]hexan-6-yl)acetic acid; Ethyl 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-carboxylate; 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-carboxylic acid; Methyl 2-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidin-4-yl)acetate; 2-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidin-4-yl)acetic acid; 2-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetic acid; Methyl 2-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetate; Methyl 2-((3R,4S)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetate; 2-((3R,4S)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetic acid; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-methylpyrimidine-5-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-methylpyrimidine-5-carboxylic acid; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyrimidine-5-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-pyrimidine-5-carboxylic acid; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)thiazole-4-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)thiazole-4-carboxylic acid; Methyl 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)butanoic acid; Methyl 3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)butanoate; Methyl (R)-3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)butanoate; (R)-3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)butanoic acid; N-(1-carbamoylcyclopropyl)-1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide; Methyl 6-((2-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)ethyl)(methyl)amino)-2,4-dimethylnicotinate; 6-((2-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)ethyl)(methyl)amino)-2,4-dimethylnicotinic acid; 1-(4-chloro-3-fluorophenyl)-N-(1-hydroxy-2-methylpropan-2-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide; 1-(4-chloro-3-fluorophenyl)-N-(2-hydroxy-2-methylpropyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide; 4-(1-(4-chloro-3-fluorophenyl)-3-ethyl-3-methyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one; N-(1-carbamoylcyclopropyl)-1-(4-chloro-3-fluorophenyl)-3-ethyl-3-methyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide; 4-(1’-(4-chloro-3-fluorophenyl)-1’,2,2’,3,5,6-hexahydrospiro[pyran-4,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-2-one; 6-(4-(1’-(4-chloro-3-fluorophenyl)-1’,2,2’,3,5,6-hexahydrospiro[pyran-4,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 4-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclopropane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-2-one; 4-(1’-(4-chloro-3-fluorophenyl)-1’,2’,4,5-tetrahydro-2H-spiro[furan-3,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-2-one; Methyl 6-(4-(1’-(4-chloro-3-fluorophenyl)-1’,2’,4,5-tetrahydro-2H-spiro[furan-3,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1’-(4-chloro-3-fluorophenyl)-1’,2’,4,5-tetrahydro-2H-spiro[furan-3,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 4-(8-(4-chloro-3-fluorophenyl)-3a-methyl-3,3a,8,8a-tetrahydro-2H-furo[3’,2’:4,5]pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one; cis-4-(8-(4-chloro-3-fluorophenyl)-3a-methyl-3,3a,8,8a-tetrahydro-2H-furo[3’,2’:4,5]pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one; 4-((3aR,8aR)-8-(4-chloro-3-fluorophenyl)-3a-methyl-3,3a,8,8a-tetrahydro-2H-furo[3’,2’:4,5]pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one; 4-((3aS,8aS)-8-(4-chloro-3-fluorophenyl)-3a-methyl-3,3a,8,8a-tetrahydro-2H-furo[3’,2’:4,5]pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Ethyl 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-1,3,4-thiadiazole-2-carboxylate; (1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-5-yl)(2,2-dimethyl-4-(1,3,4-thiadiazol-2-yl)piperazin-1-yl)methanone; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-methylthiazole-5-carboxylate; 2-(4-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-methylthiazole-5-carboxylic acid; Ethyl 2-(2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-methylthiazol-5-yl)acetate; 2-(2-(4-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-methylthiazol-5-yl)acetic acid; Methyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-5-methylthiazole-4-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-5-methylthiazole-4-carboxylic acid; 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-7,7-dimethyl-1,4-diazepan-5-one; 8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-2,8-diazaspiro[4.5]decan-1-one; 8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-2,8-diazaspiro[4.5]decan-3-one; 1-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidin-4-yl)imidazolidin-2-one; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-(trifluoromethyl)thiazole-5-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-4-(trifluoromethyl)thiazole-5-carboxylic acid; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-N,N-dimethylthiazole-4-carboxamide; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-5-yl)(4-(4-(4-hydroxypiperidine-1-carbonyl)thiazol-2-yl)-2,2-dimethylpiperazin-1-yl)methanone; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-5-yl)(2,2-dimethyl-4-(4-(morpholine-4-carbonyl)thiazol-2-yl)piperazin-1-yl)methanone; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)thiazole-4-carboxamide; Methyl 6-(4-(1-(3-fluoro-4-methylphenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(3-fluoro-4-methylphenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-8-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-8-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-8-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 6-(4-(1’-(4-chloro-3-fluorophenyl)-3,3-difluoro-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 6-(4-(1’-(4-chloro-3-fluorophenyl)-3-fluoro-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-2-en-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-((3S,4S)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetate; 2-((3S,4S)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetic acid; Methyl 2-((3R,4R)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetate; 2-((3R,4R)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetic acid; Ethyl (2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)thiazole-4-carbonyl)glycinate; (2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)thiazole-4-carbonyl)glycine; Methyl 2-((3S,4R)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetate; 2-((3S,4R)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidin-4-yl)acetic acid; Methyl 6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-5-yl)(2,2-dimethyl-4-(4-(4-methylpiperazine-1-carbonyl)thiazol-2-yl)piperazin-1-yl)methanone; Methyl 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-diethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(4-Chloro-3-fluorophenyl)-3,3-diethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)isonicotinate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)isonicotinic acid; Ethyl 3-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)isonicotinate; 3-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)isonicotinic acid; Ethyl 6-((1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidin-3-yl)amino)nicotinate; 6-((1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidin-3-yl)amino)nicotinic acid; Ethyl 6-((1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidin-3-yl)(methyl)amino)nicotinate; 6-((1-(1-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidin-3-yl)(methyl)amino)nicotinic acid hydrochloride; Methyl 6-(4-(1'-(3,4-difluorophenyl)-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1'-(3,4-difluorophenyl)-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-4-yl)acetate; 2-(2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-4-yl)acetic acid; Ethyl 2-(5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-2-yl)acetate; 2-(5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-2-yl)acetic acid; Methyl 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; 1’-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)spiro[indoline-3,3’-pyrrolidine]-2-one; 8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one; Ethyl 6-(6-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)nicotinate; 6-(6-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)nicotinic acid; Methyl 2-(1-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)piperidin-4-yl)acetate; 2-(1-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)piperidin-4-yl)acetic acid; 4-(1’-(4-chloro-3-fluorophenyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-2-one; Methyl 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-3,3-difluoro-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-3,3-difluoro-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Ethyl 2-((1R,5S)-8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-8-azabicyclo[3.2.1]octan-3-yl)acetate; 2-((1R,5S)-8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-8-azabicyclo[3.2.1]octan-3-yl)acetic acid; Methyl 6-(4-(6-(5-(4-(5-(methoxycarbonyl)-4,6-dimethylpyridin-2-yl)-2,2-dimethylpiperazine-1-carbonyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-1-yl)nicotinoyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-(1-(5-chloropyridin-2-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(6-(5-(4-(5-carboxy-4,6-dimethylpyridin-2-yl)-2,2-dimethylpiperazine-1-carbonyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-1-yl)nicotinoyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 6-(4-(1-(5-Chloropyridin-2-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(3,3-dimethyl-1-(pyridin-2-yl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; Ethyl 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-4-(pyridin-2-yl)piperidine-3-carboxylate; (cis)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-4-(pyridin-2-yl)piperidine-3-carboxylic acid; (trans)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-4-(pyridin-2-yl)piperidine-3-carboxylic acid; Methyl 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-3-methylpicolinate; 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-3-methylpicolinic acid; Methyl 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2-methoxynicotinate; 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2-methoxynicotinic acid; Methyl 6-(4-((1S,3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-((1R,3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-((3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-((1S,3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 6-(4-((1R,3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 6-(4-((3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-((1S,3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-((1R,3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-((3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-((1S,3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 6-(4-((1R,3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 6-(4-((3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-diethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1-(4-Chloro-3-fluorophenyl)-3,3-diethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)nicotinate; Methyl 5-(4-(1-(3-fluoro-4-(4-(5-(methoxycarbonyl)pyridin-3-yl)-2,2-dimethylpiperazine-1-carbonyl)phenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)nicotinate; 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)nicotinic acid; 5-(4-(4-(5-(4-(5-carboxypyridin-3-yl)-2,2-dimethylpiperazine-1-carbonyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-fluorobenzoyl)-3,3-dimethylpiperazin-1-yl)nicotinic acid; Methyl 2-(6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-((1s,3s)-1’-(4-chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-((1s,3s)-1’-(4-chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-((1r,3r)-1’-(4-chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-((1r,3r)-1’-(4-chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-((1r,3r)-1’-(4-chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-((1r,3r)-1’-(4-chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(1’-(4-chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1’-(4-Chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-(1’-(4-chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1’-(4-chloro-3-fluorophenyl)-3-methyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)propanoate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)propanoic acid; Methyl 6-(4-(1-(4-cyanocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(4-carbamoylcyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(1-(4,4-difluorocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1-(4,4-difluorocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; 4-(5-(4-(4,6-dimethylpyridin-2-yl)-2,2-dimethylpiperazine-1-carbonyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)cyclohexane-1-carbonitrile; Methyl 2-(6-(4-(1-cyclopentyl-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1-cyclopentyl-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(1-(4-cyanocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1-(4-cyanocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5-(3,4-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(3,4-Difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)-2-methylpropanoate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)-2-methylpropanoic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-8,8-dimethyl-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-8,8-dimethyl-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(4-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(4-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-(5-(3,4-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3,4-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-cyclopentyl-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-cyclopentyl-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3-fluoro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3-fluoro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(4-chloro-3,5-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(4-chloro-3,5-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3-chloro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3-chloro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3-chloro-4-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3-chloro-4-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3-chloro-4-(trifluoromethyl)phenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3-chloro-4-(trifluoromethyl)phenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(3-(4-chloro-3-fluorobenzyl)-1-isobutyl-3-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-6-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(3-(4-chloro-3-fluorobenzyl)-1-isobutyl-3-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-6-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydros piro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydros piro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydros piro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydros piro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(1’-(4-chloro-3-fluorophenyl)-3-methoxy-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1’-(4-chloro-3-fluorophenyl)-3-methoxy-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(3-fluoro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(3-fluoro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5-(3-chloro-4-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(3-chloro-4-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-(5’-(4-chloro-3-fluorophenyl)-5’,6’-dihydrospiro[cyclopentane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5’-(4-Chloro-3-fluorophenyl)-5’,6’-dihydrospiro[cyclopentane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(1,3-Dihydroisobenzofuran-5-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(4-fluorophenethyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(4-fluorophenethyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-(5-(4-fluorophenethyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 2-(6-(4-(5-(4-fluorophenethyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-(1’-(4-chloro-3-fluorophenyl)-3,3-dimethyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1’-(4-Chloro-3-fluorophenyl)-3,3-dimethyl-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(7,7-dimethyl-5-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(7,7-dimethyl-5-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5-(3-chloro-4-(trifluoromethyl)phenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(3-chloro-4-(trifluoromethyl)phenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5-(3,4-dichlorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(3,4-dichlorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-(5’-(3,4-difluorophenyl)-5’,6’-dihydrospiro[cyclopentane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5’-(3,4-Difluorophenyl)-5’,6’-dihydrospiro[cyclopentane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-((1r,3r)-1’-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-((1r,3r)-1’-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-((1s,3s)-1’-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-((1s,3s)-1’-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(1’-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1’-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5’-(3,4-difluorophenyl)-5’,6’-dihydrospiro[cyclopentane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5’-(3,4-difluorophenyl)-5’,6’-dihydrospiro[cyclopentane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5’-(4-chloro-3-fluorophenyl)-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5’-(4-chloro-3-fluorophenyl)-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-(5’-(3,4-difluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5’-(3,4-difluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(3,3-dimethyl-5’-(3,4,5-trifluorophenyl)-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(3,3-Dimethyl-5'-(3,4,5-trifluorophenyl)-5',6'-dihydrospiro[cyclobutane-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclobutane-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclobutane-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(1’-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1’-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1’,2’-dihydrospiro[cyclobutane-1,3’-pyrrolo[3,2-b]pyridine]-5’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5-(4-chloro-3,5-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3,5-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5’-(4-chloro-3-fluorophenyl)-5’,6’-dihydrospiro[cyclopentane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5’-(4-chloro-3-fluorophenyl)-5’,6’-dihydrospiro[cyclopentane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5’-(3,4-difluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5’-(3,4-Difluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-(5’-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5’-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3,4-dichlorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3,4-dichlorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(3-chloro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate 2-(6-(4-(5-(3-chloro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-8-methoxy-7,7-dimethyl-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-8-methoxy-7,7-dimethyl-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-6-methoxy-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-6-methoxy-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(3-(4-chloro-3-fluorophenyl)-1-isobutyl-3-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-6-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(3-(4-chloro-3-fluorophenyl)-1-isobutyl-3-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-6-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-6-hydroxy-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 8-(4-(5’-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-8-oxooctanoate; 8-(4-(5’-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-8-oxooctanoic acid; N-(37-(4-(5’-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-carbonyl)-3,3-dimethylpiperazin-1-yl)-3-methyl-4,17,30,37-tetraoxo-7,10,13,20,23,26-hexaoxa-3,16,29-triazaoctatriacontyl)-N-methylpalmitamide; Methyl 4-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,6-dimethylnicotinate; 4-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,6-dimethylnicotinic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-6-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-6-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; 1-(1-((5’-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5’,6’-dihydrospiro[cyclobutane-1,7’-pyrrolo[2,3-b]pyrazine]-2’-yl)sulfonyl)piperidin-4-yl)imidazolidin-2-one; Methyl 2-(6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrazino[2,3-b][1,4]oxazine-7-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrazino[2,3-b][1,4]oxazine-7-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; tert-Butyl 2-(4-(5-(2-methoxy-2-oxoethyl)pyridin-2-yl)-2,2-dimethylpiperazine-1-carbonyl)-7,7-dimethyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(4-Chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; Methyl 6-(4-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(3-Fluoro-4-(trifluoromethyl)phenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(7,7-Dimethyl-5-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(7,7-Dimethyl-5-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(1-(4-Cyclopropylphenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(4-Cyclopropylphenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(4-Chloro-3-fluorophenyl)-3,7,7-trimethyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-3,7,7-trimethyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-2-carbonyl)-3,3-dimethylpiperazin-1-yl)pyridin-3-yl)acetic acid; 4-(5'-(3,4-difluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutane-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazin-2-one; Particularly preferably, it is selected from any one of the above compounds, a pharmaceutically acceptable salt or solvate thereof.

[0165] The present invention also relates to each of the intermediates described in the Examples section of the present specification below, in non-salt form and / or non-solvate form, or in the form of a salt or solvate (e.g., a pharmaceutically acceptable salt or solvate) of each compound, and includes any one of these intermediates. Such intermediates can be used particularly in the synthesis of the compounds of formula (I).

[0166] To those skilled in the field of synthetic chemistry, various methods for preparing the compounds of general formula (I) and their pharmaceutically acceptable salts and solvates will become readily apparent. For example, the compounds of the present invention can be prepared according to or similar to the synthetic routes described in detail in the Examples section. In particular, the compounds of formula (I) can be synthesized according to the methods described in the following general scheme (general cleavage). Schematic overview:

[0167]

Chemical formula

[0168] The compounds of formula (I) can be obtained from the precursor (II)-A according to the general cleavage A:

[0169]

Chemical formula

[0170] Z N When Z is a hydrogen atom: - By N-derivatization known to those skilled in the art using an appropriate partner (based on the studies described in Chem. Rev., 2016, 116, 12564 - 12649, Chem. Rev. 2019, 119, 11857 - 11911, Chem. Rev. 2019, 119, 12491 - 12523, Chem. Rev. 2019, 119, 11245 - 11290, Chem. Soc. Rev., 2014, 3525 - 3550, or Nature, 2020, 581, 415 - 420) - By aniline synthesis from an appropriate aldehyde or keto derivative (based on the studies described in Org. Lett., 2012, 14, 5606 - 5609 or Nature, 2020, 584, 75 - 81).

[0171] Z N When Z is a methyl group: - By N-arylation using an appropriate arene precursor (based on the study described in Org. Lett., 2013, 15, 5452 - 5455).

[0172] Z N When Z is a benzoic acid group: - By metal-catalyzed debenzoylative N-arylation using an appropriate organometallic partner (based on the study described in J. Org. Chem., 2006, 71, 219 - 224) Z N When Z is a substituted carbonyl group: - By rearrangement of the corresponding amide derivative (based on the study described in Synlett 2013, 24, 1448 - 1454), or by rearrangement of the corresponding carbamate derivative (based on the study described in J. Am. Chem. Soc., 2019, 141, 7262 - 7265) - By metal-catalyzed deacylative N-arylation using a suitable halogenated or pseudo-halogenated aryl (based on studies described in Org. Lett. 2021, 23, 3, 687 - 691 or J. Org. Chem., 2012, 77, 9236 - 9239) The compound of formula (I) can be obtained from the precursor (II)-B1 according to the general cleavage B1:

[0173]

Chemical formula

[0174] Z L When Z is a hydrogen atom (based on studies described in ARKIVOC 2013, 1, 154 - 174, ARKIVOC 2001, 1, 242 - 268 or Synthesis 2011, 20, 3209 - 3219): - Following N-oxidation, by a sequence that gives a carboxylic acid, sulfonic acid or sulfinic acid and subsequent amide, sulfonamide or sulfinamide synthesis using a suitable amine. - Following N-oxidation, by a sequence that results in the conversion of Z L to a halogen or pseudo-halogen, followed by the following conversion or sequence. - Z L By carbon - hydrogen bond activation using a metal that results in the conversion of Z to a halogen, pseudo-halogen, or organometallic group, followed by the following conversion or sequence.

[0175] Z L When Z is a hydroxy group (based on studies described in Org. Process Res. Dev. 2004, 8, 62 - 71 or Tet. Lett., 1992, 33, 1181 - 1184): - By a conversion or sequence known to those skilled in the art of converting Z L to a halogen or pseudo-halogen, followed by the following conversion or sequence.

[0176] Z LWhen it is a halogen, pseudohalogen, or organometallic group: - By direct metal-catalyzed amino-carbonylation reaction using an appropriate amine, sulfinamide or sulfonamide synthesis (based on the research described in RSC Adv., 2014, 4, 10367 - 10389 or Synthesis, 2008, 311 - 312) - Conversions or sequences known to those skilled in the art that result in carboxylic acid, sulfonic acid or sulfinic acid, followed by amide, sulfonamide or sulfinimide synthesis using an appropriate amine (based on the research described in J. Org. Chem., 2008, 73, 3967 - 3969) The compound of formula (I) can be obtained from precursor (II)-B2 according to general cleavage B2:

[0177]

Chemical formula

[0178] For example, by conversions or sequences known to those skilled in the art that result in tertiary amide, sulfonamide or sulfinimide, including deprotonation and N-substitution with an appropriate partner, or a sequence involving metal-catalyzed N-derivatization.

[0179] The compound of formula (I) can be obtained from precursor (II)-C1 according to general cleavage C1:

[0180]

Chemical formula

[0181] Z A2 is a halogen or pseudohalogen, and when R A1 , Y1 or Y2 is linked to a carbonyl (based on the research described in ChemistryOpen, 2020, 9, 100 - 17, or Acc. Chem. Res. 2008, 41, 11, 1545 - 1554): - By halogen-metal exchange followed by derivatization via metal-catalyzed coupling with a suitable partner. - By halogen-metal exchange followed by nucleophilic displacement or nucleophilic addition to a suitable partner. - By direct nucleophilic substitution of a halogen or pseudohalogen with a suitable nucleophile.

[0182] Z A2 is a hydrogen atom, and R A1 , Y1 or Y2 is linked to a carbonyl (based on the studies described in ChemistryOpen, 2020, 9, 100 - 17, or Acc.Chem.Res. 2008, 41, 11, 1545 - 1554): - By metallation followed by derivatization via metal-catalyzed coupling with a suitable partner. - By metallation followed by nucleophilic substitution or nucleophilic addition to a suitable partner. - By direct nucleophilic substitution of a halogen or pseudohalogen with a suitable nucleophile. - By oxidative coupling (based on the studies described in Angew.Chem.Int.Ed. 2017, 56, 5921 - 5925) Z A2 is a hydrogen atom and Y1 is a bond: - By photoredox-catalyzed α-derivatization of an amine with a suitable radical acceptor (based on the studies described in J.Am.Chem.Soc. 2020, 15, 142, 11972 - 11977, or Chem.Rev., 2013, 113, 5322 - 5363).

[0183] Z A2 is a halogen or pseudohalogen and Y2 is a bond: - By metal-catalyzed coupling with a suitable partner (based on the studies described in Org.Lett., 2009, 11, 23, 5514 - 5517) The compounds of formula (I) can be obtained from the precursors (II)-C2, (II)-C3 or (II)-C4 by general cleavage C 2 / 3 / 4 according to:

[0184]

Chemical formula

[0185] - by [2+1] cycloaddition with a suitable partner (based on the studies described in Chem. Rev. 2017, 117, 18, 11651-11679). - by epoxidation followed by epoxide ring opening with a suitable partner (based on the studies described in Chem. Soc. Rev., 2011, 40, 1722-1760, J. Am. Chem. Soc. 1993, 115, 19, 8867-8868, or Synlett, 2005, 8, 1199-1222). - by [2+2] cycloaddition with a suitable partner (based on the studies described in Eur. J. Org. Chem., 2020, 10, 1310-1326, or Chem. Rev. 2016, 116, 9748-9815). - by [2+2] cycloaddition with a suitable carbonyl, finally followed by the corresponding oxetane ring opening with a suitable partner (based on the studies described in Molecules, 2013, 18, 11384-11428, or Chem. Rev., 2016, 116, 12150-12233). - by [2+3] cycloaddition with a suitable partner (based on the studies described in Beilstein J. Org. Chem. 2020, 16, 3015-3031, or Chem. Rev. 2005, 105, 2765-2809). - by [2+4] Diels-Alder cycloaddition with a suitable diene or a suitable dienophile (based on the studies described in Chem. Rev. 1942, 31, 2, 319-523, or Chem. Soc. Rev., 2018, 47, 7926). - By nucleophilic addition known to those skilled in the art using (II)-C3 containing a conjugated double bond (where Y2 is -CZ-) or an imine (where Y2 is N), or an α,β-unsaturated carbonyl (where Y1 is -CZ2-C(O)-), sulfonyl (where Y1 is -CZ2-S(O)2-), or imine (where Y1 is a bond) containing (II)-C4. - By electrophilic addition known to those skilled in the art to the exocyclic double bond on (II)-C4 (where Y1 is -CZ-).

[0186] In addition, the specific intermediates (II)-C2, (II)-C3, and (II)-C4 can be obtained using synthetic strategies present in the dearomatization of the respective aromatic compounds or can be used as precursors for obtaining the compounds of formula (I) (based on the studies described in Synlett, 2020, 31, 1775 - 1788, Org. Chem. Front., 2020, 7, 3967 - 3998, Tetrahedron, 2015, 71, 3549 - 359, Org. Lett. 2019, 21, 4459 - 4463, Synthesis, 2022, 54, 92 - 110, Chem Sci. 2017, 8, 7112 - 7118, Org. Biomol. Chem., 2014, 12, 4807 - 4815, or Tetrahedron, 2019, 75, 2063 - 2097).

[0187] The compounds of formula (I) can be obtained from the precursors (II)-D1, (II)-D2, (II)-D3, or (II)-D6 according to the general cleavage D 1 / 2 / 3 / 6 as follows:

[0188]

Chemical Structure

[0189] When Z1 is hydrogen or an organometallic group, or a halogen or pseudohalogen, and Z2, Z Y1 、Z Y2 、Z Y3 are each a halogen or pseudohalogen, or hydrogen or an organometallic group: - By a metal-catalyzed coupling reaction known to those skilled in the art.

[0190] When Z1 is hydrogen, or a halogen or pseudohalogen, and Z2, Z Y1 、Z Y2 、Z Y3 are each a halogen or pseudohalogen, or hydrogen: - Following the induced metallation, by an intramolecular nucleophilic substitution or aromatic nucleophilic substitution known to those skilled in the art. - By a nucleophilic substitution or aromatic nucleophilic substitution known to those skilled in the art.

[0191] When Z1 and Z2, Z Y1 、Z Y2 、Z Y3 are all halogens or pseudohalogens: - By metal-catalyzed reductive coupling (based on the studies described in Chem. Eur. J. 2014, 20, 15334 - 15338, or Chem. Eur. J. 2014, 20, 6828 - 6842).

[0192] When Z1 and Z2, Z Y1 、Z Y2 、Z Y3 are suitable partners: - By a suitable cycloaddition described in General Disconnection C 2 / 3 / 4 The compound of formula (I) can be obtained from the precursor (II)-D4 or (II)-D5 according to General Disconnection D 4 / 5 as follows:

[0193]

Chemical Formula

[0194] When Z N is carbonyl: - By a reductive amination reaction or amide synthesis known to those skilled in the art. - By the Petasis reaction (based on the research described in Chem. Rev. 2019, 119, 11245 - 11290, or RSC Adv., 2015, 5, 76337 - 76341).

[0195] Z N is a halogen or pseudohalogen, or an organometallic group: - By nucleophilic substitution known to those skilled in the art. - By a metal - catalyzed coupling reaction (based on the research described in Chem. Rev. 2016, 116, 19, 12564 - 12649, Chem. Soc. Rev., 2014, 43, 3525 - 3550 or Chem. Rev. 2019, 119, 24, 12491 - 12523).

[0196] The compound of formula (I) can be obtained from the precursor (II) - E1 according to the general cleavage E1:

[0197]

Chemical formula

[0198] - By a cross - coupling reaction, reductive coupling or cross - metathesis known to those skilled in the art. - By the Petasis or Mannich reaction (based on the research described in Chem. Rev. 2019, 119, 11245 - 11290, RSC Adv., 2015, 5, 76337 - 76341, Org. Chem. Front., 2018, 5, 1049 - 1066, or Synthesis 2013, 45, 2769 - 2812), respectively).

[0199] The compound of formula (I) can be obtained from the precursor (II) - E2 according to the general cleavage E2:

[0200]

Chemical formula

[0201] - RN by double reductive amination using -NH2 - R N by double (aromatic) nucleophilic substitution using -NH2 - R N by one - pot reductive amination and nucleophilic substitution using -NH2 The compound of formula (I) can be obtained from the precursors (II) - E3 and / or (II) - E4 by general cleavage E 3 / 4 as follows:

[0202]

Chemical formula

[0203] - By heterocyclic ring synthesis from the precursor (II) - E3 known to those skilled in the art, more specifically, by the specific methods described in Topics in Current Chemistry, 2019, 377, 21, Synthetic Communications, 2020, 50, 1251 - 1285, Org.Chem.Front., 2019, 6, 2120 - 2141, Chem.Rev.2011, 111, 4, 2937 - 2980, or Synlett, 2011, 2387 - 2391. - By cycloaddition reactions that result in aromatic heterocyclic synthesis known to those skilled in the art, more specifically, by sequences based on the research described in Org.Chem.Front., 2014, 1, 1010 - 1015, J.Am.Chem.Soc.1999, 121, 54 - 62, Acc.Chem.Res.2020, 53, 4, 773 - 781 or C.R.Chimie, 2017, 20, 643 - 647. - By cycloaddition that results in non - aromatic heterocyclic synthesis known to those skilled in the art, more specifically, by hetero - arene transformation based on the research described in Angew.Chem.Int.Ed., 2015, 54, 11765 - 11769, or Chem.Rev.2021, 121, 3892 - 4044.

[0204] The above - mentioned general cleavages A, B1, B2, C1, C 2 / 3 / 4 , D1 / 2 / 3 / 6 , D 4 / 5 , E1, E2, E 3 / 4 , and by using available documents and combining them, any compound of formula (I) can be synthesized from commercially available compounds or from compounds whose synthesis is already described in the literature or compounds that can be obtained using methods known in the art.

[0205] The following definitions apply throughout this specification and the claims, unless otherwise specifically indicated. The term "hydrocarbon group" refers to a group consisting of carbon atoms and hydrogen atoms.

[0206] The term "alicyclic" is used in relation to a cyclic group and indicates that the corresponding cyclic group is non-aromatic. As used herein, the term "alkyl" refers to a monovalent saturated acyclic (i.e., acyclic) hydrocarbon group that may be linear or branched. Thus, an "alkyl" group does not contain any carbon-carbon double bonds or any carbon-carbon triple bonds. "C 1~5 alkyl" represents an alkyl group having from 1 to 5 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 refers to methyl or ethyl, and even more preferably refers to methyl.

[0207] As used herein, the term "alkenyl" refers to a monovalent unsaturated acyclic hydrocarbon group that may be linear or branched and contains one or more (e.g., one or two) carbon-carbon double bonds, but does not contain any carbon-carbon triple bonds. "C 2~5The term "alkenyl" refers to an alkenyl group having from 2 to 5 carbon atoms. Preferred exemplary alkenyl groups are ethenyl, 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.

[0208] As used herein, the term "alkynyl" may be straight-chain or branched, and refers to a monovalent unsaturated acyclic hydrocarbon group containing one or more (e.g., one or two) carbon-carbon triple bonds, and may contain one or more (e.g., one or two) carbon-carbon double bonds. "C 2~5 alkynyl" refers to an alkynyl group having from 2 to 5 carbon atoms. Preferred exemplary alkynyl groups are ethynyl, propynyl (e.g., propargyl), or butynyl. Unless otherwise defined, the term "alkynyl" preferably refers to C 2~4 alkynyl.

[0209] As used herein, the term "alkylene" refers to an alkanediyl group, i.e., a divalent saturated acyclic hydrocarbon group that may be straight-chain or branched. "C 1~5 alkylene" represents an alkylene group having from 1 to 5 carbon atoms, and the term "C 0~3 alkylene" refers to a covalent bond (corresponding to the option "C0 alkylene") or C 1~3It indicates the presence of alkylene. Preferred exemplary alkylene groups 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 (especially linear C 1~4 alkylene-containing), more preferably refers to methylene or ethylene, and even more preferably refers to methylene.

[0210] As used herein, the term "alkenylene" refers to an alkenediyl group, i.e., a divalent unsaturated acyclic hydrocarbon group that may be linear or branched and contains one or more (e.g., one or two) carbon-carbon double bonds, but does not contain any carbon-carbon triple bonds. "C 2~5 alkenylene" represents an alkenylene group having 2 to 5 carbon atoms. Unless otherwise defined, the term "alkenylene" preferably refers to C 2~4 alkenylene (especially linear C 2~4 alkenylene-containing).

[0211] As used herein, the term "alkynylene" refers to an alkynediyl group, i.e., a divalent unsaturated acyclic hydrocarbon group that may be linear or branched and contains one or more (e.g., one or two) carbon-carbon triple bonds and may contain one or more (e.g., one or two) carbon-carbon double bonds. "C 2~5 alkynylene" represents an alkynylene group having 2 to 5 carbon atoms. Unless otherwise defined, the term "alkynylene" preferably refers to C 2~4 alkynylene (especially linear C 2~4 alkynylene-containing).

[0212] As used herein, the term "carbocyclic" (or "carbocyclic ring") refers to a hydrocarbon ring group including monocyclic rings as well as bridged rings, spiro rings and / or fused ring systems (which may be composed of, for example, two or three rings), and said ring group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. Unless otherwise defined, "carbocyclic" preferably refers to aryl, cycloalkyl or cycloalkenyl.

[0213] As used herein, the term "heterocyclic" (or "heterocyclic ring") refers to a ring group including monocyclic rings as well as bridged rings, spiro rings and / or fused ring systems (which may be composed of, for example, two or three rings), said ring group containing one or more (e.g., 1, 2, 3, or 4, etc.) ring heteroatoms independently selected from O, S and N, with the remaining ring atoms being carbon atoms, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further, said ring group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. For example, each heteroatom-containing ring contained in said ring group may contain 1 or 2 O atoms and / or 1 or 2 S atoms (which may optionally be oxidized) and / or 1, 2, 3 or 4 N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is from 1 to 4, and there is at least one carbon ring atom (which may optionally be oxidized) present in the corresponding heteroatom-containing ring. Unless otherwise defined, "heterocyclic" preferably refers to heteroaryl, heterocycloalkyl or heterocycloalkenyl.

[0214] As used herein, the term "aryl" refers to an aromatic hydrocarbon ring group that includes monocyclic aromatic rings as well as bridged and / or fused ring systems containing at least one aromatic ring (e.g., a ring system composed of two or three fused rings, at least one of these fused rings being aromatic; or a bridged ring system composed of two or three rings, at least one of these bridged rings being aromatic). When aryl is a bridged and / or fused ring system that contains, in addition to one or more aromatic rings, at least one non-aromatic ring (e.g., a saturated or unsaturated alicyclic ring), one or more carbon ring atoms in each non-aromatic ring may optionally be oxidized (i.e., to form an oxo group). "Aryl" can refer to, for example, phenyl, naphthyl, dihydronaphthyl (i.e., 1,2-dihydronaphthyl), tetrahydronaphthyl (i.e., 1,2,3,4-tetrahydronaphthyl), indanyl, indenyl (e.g., 1H-indenyl), anthracenyl, phenanthrenyl, 9H-fluorenyl, or azulenyl. 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.

[0215] As used herein, the term "heteroaryl" (or "aromatic heterocycle") refers to an aromatic ring group containing a monocyclic aromatic ring as well as a bridged ring and / or a fused ring system containing at least one aromatic ring (e.g., a ring system composed of two or three fused rings, at least one of these fused rings being aromatic; or a bridged ring system composed of two or three rings, at least one of these bridged rings being aromatic), said aromatic ring group containing one or more (e.g., 1, 2, 3, or 4, etc.) ring heteroatoms independently selected from O, S, and N, the remaining ring atoms being carbon atoms, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further, one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring contained in the aromatic ring group may contain 1 or 2 O atoms and / or 1 or 2 S atoms (which may optionally be oxidized) and / or 1, 2, 3, or 4 N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is from 1 to 4 and that at least one carbon ring atom (which may optionally be oxidized) is present in the corresponding heteroatom-containing ring. "Heteroaryl" includes, for example, thienyl (i.e., thiophenyl), benzo[b]thienyl, naphtho[2,3-b] Thienyl, thianthrenyl, furyl (i.e., furanyl), benzofuranyl, isobenzofuranyl, chromanyl, chromenyl (e.g., 2H-1-benzopyranyl or 4H-1-benzopyranyl), isochromenyl (e.g., 1H-2-benzopyranyl), chromonyl, xanthenyl, phenoxathiinyl, pyrrolyl (e.g., 1H-pyrrolyl), imidazolyl, pyrazolyl, pyridyl (i.e., pyridinyl; e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl), pyrazinyl, pyrimidinyl, pyridazinyl, indolyl (e.g., 1H-indolyl), isoindolyl, indazolyl, indolizinyl, purinyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, cinnolinyl, pteridinyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl (e.g., [1,10]phenanthrolinyl, [1,7]phenanthrolinyl, or [4,7]phenanthrolinyl), phenazinyl, thiazolyl, isothiazolyl, phenothiazinyl, oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl (i.e., furazanyl), or 1,3,4-oxadiazolyl), thiadiazolyl (e.g., 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, or 1,3,4-thiadiazolyl), phenoxazinyl, pyrazolo[1,5-a]pyrimidinyl (e.g., pyrazolo[1,5-a]pyrimidin-3-yl), 1,2-benzisoxazol-3-yl, benzothiazolyl, benzothiadiazolyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzo[b]thiophenyl (i.e., benzothienyl), 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), furo[2,3-c]pyridinyl, dihydrofuropyridinyl (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, benzodioxanyl (e.g., 1,3-benzodioxanyl or 1,4-benzodioxanyl), or coumarinyl. 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 containing one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be oxidized, one or more carbon ring atoms may be oxidized, and even more preferably, "heteroaryl" refers to a 5- or 6-membered monocyclic ring containing one or more (e.g., 1, 2, or 3) ring heteroatoms independently selected from O, S, and N, one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be oxidized, one or more carbon ring atoms may be oxidized. Further, unless otherwise defined, particularly preferred examples of "heteroaryl" include pyridinyl (e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl), imidazolyl, thiazolyl, 1H-tetrazolyl, 2H-tetrazolyl, thienyl (i.e., thiophenyl), or pyrimidinyl.,

[0216] As used herein, the term "cycloalkyl" refers to a saturated hydrocarbon ring group that includes monocyclic rings as well as bridged, spiro, and / or fused ring systems (e.g., may be composed of two or three rings; e.g., a fused ring system composed of two or three fused rings, etc.). "Cycloalkyl" can refer to, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, decalinyl (i.e., decahydronaphthyl), or adamantyl. Unless otherwise defined, "cycloalkyl" preferably refers to C 3~11 cycloalkyl, more preferably refers to C 3~7 cycloalkyl. Particularly preferred "cycloalkyl" is a monocyclic saturated hydrocarbon ring having 3 to 7 ring members. Further, unless otherwise defined, particularly preferred examples of "cycloalkyl" include cyclohexyl or cyclopropyl, particularly cyclohexyl.

[0217] As used herein, the term "heterocycloalkyl" refers to a saturated cyclic group including monocyclic rings as well as bridged, spiro and / or fused ring systems (e.g., may be composed of two or three rings; such as a fused ring system composed of two or three fused rings, etc.), said cyclic group containing one or more (e.g., 1, 2, 3, or 4, etc.) ring heteroatoms independently selected from O, S and N, with the remaining ring atoms being carbon atoms, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further, one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring contained in said saturated cyclic group may contain 1 or 2 O atoms and / or 1 or 2 S atoms (which may optionally be oxidized) and / or 1, 2, 3 or 4 N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is from 1 to 4 and there is at least one carbon ring atom (which may optionally be oxidized) present in the corresponding heteroatom-containing ring. "Heterocycloalkyl" may refer to, for example, aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, piperazinonyl (e.g., piperazin-2-one-1-yl or piperazin-3-one-1-yl), azepanyl, diazepanyl (e.g., 1,4-diazepanyl), oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, morpholinyl (e.g., morpholin-4-yl), thiomorpholinyl (e.g., thiomorpholin-4-yl), oxazepanyl, oxiranyl, oxetanyl, tetrahydrofuranyl, 1,3-dioxolanyl, tetrahydropyranyl, 1,4-dioxanyl, oxepanyl, thietanyl, thietanyl, tetrahydrothiophenyl (i.e., thioranyl), 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 that is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), the ring group containing one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be oxidized, and one or more carbon ring atoms may be oxidized. More preferably, "heterocycloalkyl" refers to a 5- to 7-membered saturated monocyclic ring group containing one or more (e.g., 1, 2, or 3) ring heteroatoms independently selected from O, S, and N, one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be oxidized, and one or more carbon ring atoms may be oxidized. Further, unless otherwise defined, particularly preferred examples of "heterocycloalkyl" include tetrahydropyranyl, piperidinyl, piperazinyl, piperazinonyl, morpholinyl, pyrrolidinyl, or tetrahydrofuranyl.

[0218] As used herein, the term "cycloalkenyl" refers to an unsaturated alicyclic (non-aromatic) hydrocarbon ring group including a monocyclic ring as well as a bridged ring, a spiro ring, and / or a fused ring system (e.g., which may be composed of two or three rings; e.g., a fused ring system composed of two or three fused rings, etc.), the hydrocarbon ring group containing one or more (e.g., one or two) carbon-carbon double bonds and no carbon-carbon triple bonds. "Cycloalkenyl" may refer to, for example, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, or cycloheptadienyl. Unless otherwise defined, "cycloalkenyl" preferably refers to C 3~11 refers to cycloalkenyl, more preferably C 3~7Refers to 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.

[0219] As used herein, the term "heterocycloalkenyl" refers to an unsaturated alicyclic (non-aromatic) ring group including monocyclic rings as well as bridged rings, spiro rings and / or fused ring systems (e.g., which may be composed of two or three rings; e.g., a fused ring system composed of two or three fused rings, etc.), said ring group containing one or more (e.g., 1, 2, 3, or 4, etc.) ring heteroatoms independently selected from O, S and N, the remaining ring atoms being carbon atoms, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further, said ring group contains at least one double bond between adjacent ring atoms and does not contain any triple bonds between adjacent ring atoms. For example, each heteroatom-containing ring contained in said unsaturated alicyclic ring group may contain 1 or 2 O atoms and / or 1 or 2 S atoms (which may optionally be oxidized) and / or 1, 2, 3 or 4 N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is from 1 to 4 and that at least one carbon ring atom (which may optionally be oxidized) is present in the corresponding heteroatom-containing ring. "Heterocycloalkenyl" may refer to, for example, imidazolinyl (e.g., 2-imidazolinyl (i.e., 4,5-dihydro-1H-imidazolyl), 3-imidazolinyl, or 4-imidazolinyl), tetrahydropyridinyl (e.g., 1,2,3,6-tetrahydropyridinyl), dihydropyridinyl (e.g., 1,2-dihydropyridinyl or 2,3-dihydropyridinyl), pyranyl (e.g., 2H-pyranyl or 4H-pyranyl), thiopyranyl (e.g., 2H-thiopyranyl or 4H-thiopyranyl), dihydropyranyl, dihydrofuranyl, 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 a 3- to 11-membered unsaturated alicyclic ring group that is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), the ring group contains one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be oxidized, one or more carbon ring atoms may be oxidized, the ring group contains at least one double bond between adjacent ring atoms and does not contain any triple bonds 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., 1, 2, or 3) ring heteroatoms independently selected from O, S, and N, one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be oxidized, one or more carbon ring atoms may be oxidized, the ring group contains at least one double bond between adjacent ring atoms and does not contain any triple bonds between adjacent ring atoms.

[0220] As used herein, the term "halogen" refers to fluoro (-F), chloro (-Cl), bromo (-Br), or iodo (-I). 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 fluoro, chloro, bromo, and iodo, preferably all fluoro atoms. The maximum number of halogen atoms is limited by the number of available bonding sites and thus depends on the number of carbon atoms in the alkyl portion of the haloalkyl group. "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.

[0221] Unless otherwise clearly indicated or unless the context is inconsistent, the terms "bond" and "covalent bond" are used synonymously herein. 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" or "may" are used, the invention specifically relates to both possibilities, i.e., whether the corresponding feature is present or, alternatively, whether the corresponding feature is absent. For example, the expression "X may be substituted with Y" (or "X may be replaced with Y") means that X is either substituted with Y or unsubstituted. Similarly, when a component of a composition is indicated to be "optional", the invention specifically relates to both possibilities, i.e., whether the corresponding component is present (contained in the composition) or whether the corresponding component is absent from the composition.

[0222] In this specification, various groups are referred to as "optionally substituted". In general, these groups may have one or more substituents, such as 1, 2, 3 or 4 substituents. It will be understood that the maximum number of substituents is limited by the number of available bonding sites on the substituted moiety. Unless otherwise defined, the "optionally substituted" groups referred to herein preferably have 2 or fewer substituents, particularly may have only 1 substituent. Further, unless otherwise defined, it is preferred that there are no optional substituents, i.e., the corresponding group is unsubstituted.

[0223] One of ordinary skill in the art will recognize that the substituents included in the compounds of the present invention may be attached to the remainder of each compound via several different positions of the corresponding specific substituent. Unless otherwise defined, the preferred attachment positions for the various specific substituents are as illustrated by the examples.

[0224] As used herein, unless otherwise expressly indicated or unless the context clearly dictates otherwise, the terms "a," "an," and "the" are used interchangeably with "one or more" and "at least one." Thus, for example, a composition containing "a" compound of formula (I) can be construed to refer to a composition containing "one or more" compounds of formula (I).

[0225] Whenever a numerical range is provided / disclosed herein, it should be understood that every value and subrange subsumed by that numerical range is intended to be encompassed within the scope of the invention. Thus, the invention specifically and individually relates to each value within the numerical ranges disclosed herein, and to each subrange subsumed by the numerical ranges disclosed herein.

[0226] As used herein, the term "about" preferably refers to ±10% of the indicated numerical value, more preferably to ±5% of the indicated numerical value, and in particular to the exact numerical value indicated. When the term "about" is used in connection with the endpoints of a range, this preferably refers to a range from -10% of the indicated lower endpoint value to +10% of the indicated upper endpoint value, more preferably to a range from -5% of the lower endpoint to +5% of the upper endpoint, and even more preferably to the range defined by the exact numerical values of the lower and upper endpoints.

[0227] As used herein, the term "comprising" (or "comprise", "comprises", "contain", "contains", or "containing") has the meaning of "including, among other things", i.e., "including... among additional optional elements", unless otherwise clearly indicated or inconsistent with the context. In addition, this term also includes the narrower meanings of "consisting essentially of" and "consisting of". For example, the term "A comprising B and C" has the meaning of "A including, among other things, B and C", and A may further contain additional optional elements (e.g., "A containing B, C and D" is also included), but this term also includes the meaning of "A consisting essentially of B and C" and the meaning of "A consisting of B and C" (i.e., A does not contain components other than B and C).

[0228] The scope of the present invention encompasses all pharmaceutically acceptable salt forms of the compounds of formula (I) which can be formed, for example, by protonation with an inorganic or organic acid of an atom having a lone pair of electrons susceptible to protonation, such as an amino group, or as a salt of an acidic 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; heterocyclic aromatic amine salts such as pyridine salt, picoline 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, mineral acid salts such as hydrochloride, hydrobromide, hydroiodide, sulfate (e.g., sulfate or bisulfate, etc.), nitrate, phosphate (e.g., phosphate, hydrogen phosphate, or dihydrogen phosphate, etc.), carbonate, bicarbonate, perchlorate, borate, or thiocyanate; organic acid salts such as acetate, propionate, butyrate, pentanoate, 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), camphorsulfonate, glucoheptanoate, or pivalate; sulfonate salts such as methanesulfonate (mesylate), ethanesulfonate (esylate), 2-hydroxyethanesulfonate (isethionate), benzenesulfonate (besylate), p-toluenesulfonate (tosylate), 2-naphthalenesulfonate (napsylate), 3-phenylsulfonate, or camphorsulfonate; glycerophosphate; and acidic amino acid salts such as aspartate or glutamate. Further pharmaceutically acceptable salts are described in the literature, for example, Stahl PH & Wermuth CG (eds.), "Handbook of Pharmaceutical Salts: Properties, Selection, and Use", Wiley-VCH, 2002 and the references cited therein. Preferred pharmaceutically acceptable salts of the compound of formula (I) include hydrochloride, hydrobromide, mesylate, sulfate, tartrate, fumarate, acetate, citrate, and phosphate. Particularly preferred pharmaceutically acceptable salts of the compound of formula (I) are hydrochloride. Accordingly, a compound of formula (I) comprising any one of the specific compounds of formula (I) described herein is preferably in the form of hydrochloride, hydrobromide, mesylate, sulfate, tartrate, fumarate, acetate, citrate, or phosphate, and particularly preferably the compound of formula (I) is in the form of hydrochloride.

[0229] The present invention also relates specifically to a compound of formula (I) comprising any one of the specific compounds of formula (I) described herein in non-salt form. Furthermore, the scope of the present invention encompasses, for example, solvates with water (i.e., as hydrates) or solvates with organic solvents such as, for example, methanol, ethanol, isopropanol, acetic acid, ethyl acetate, ethanolamine, DMSO, or acetonitrile, of the compound of formula (I). All physical forms, including any amorphous or crystalline form (i.e., polymorph) of the compound of formula (I), are also encompassed within the scope of the present invention. It should be understood that such solvates and physical forms of pharmaceutically acceptable salts of the compound of formula (I) are likewise encompassed by the present invention.

[0230] Furthermore, the compounds of formula (I) may exist in the form of different isomers, in particular stereoisomers (including, for example, geometric isomers (or cis / trans isomers), enantiomers and diastereomers) or tautomers (including, in particular, prototropic tautomers such as keto / enol tautomers or thione / thiol tautomers). All such isomers of the compounds of formula (I) are intended to be part of the present invention, either as mixtures or in pure or substantially pure form. With regard to stereoisomers, the present invention encompasses the isolated optical isomers of the compounds according to the invention and any mixtures thereof (including, in particular, racemic mixtures / racemates). Racemates can be resolved by physical methods such as fractional crystallization, separation or crystallization of diastereomeric derivatives, or separation by chiral column chromatography. The individual optical isomers can also be obtained from the racemate via salt formation with an optically active acid followed by crystallization. The present invention further encompasses any tautomers of the compounds of formula (I). It will be understood that some compounds may exhibit tautomerism. In such cases, the formulae provided herein explicitly depict only one of the possible tautomers. The formulae and chemical names provided herein are intended to encompass any tautomers of the corresponding compounds and are not limited to the specific tautomers depicted by the drawings or identified by the name of the compound.

[0231] The scope of the present invention also encompasses compounds of formula (I) in which one or more atoms are replaced by specific isotopes of the corresponding atoms. 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 compounds of formula (I) that are enriched in deuterium. Naturally occurring hydrogen consists of approximately 99.98 mol% hydrogen-1 ( 1 H) and approximately 0.0156 mol% deuterium ( 2is an isotope mixture containing H or D). The deuterium content at one or more hydrogen positions in the compound of formula (I) can be increased using deuteration techniques known in the art. For example, the compound of formula (I) or the reactants or precursors used in the synthesis of the compound of formula (I) can be subjected to an H / D exchange reaction using, for example, heavy water (D2O). Further 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 deuterium content can be determined using, for example, mass spectrometry or NMR spectroscopy. Unless otherwise specifically indicated, the compound of formula (I) is preferably not enriched in deuterium. Thus, it is preferred that hydrogen atoms or 1 H hydrogen atoms that occur naturally in the compound of formula (I) are present.

[0232] The present invention also encompasses compounds of formula (I) in which one or more atoms are replaced by the positron-emitting isotopes of the corresponding atoms, such as 18 F, 11 C, 13 N, 15 O, 76 Br, 77 Br, 120 I and / or 124 I, etc. Such compounds can be used as tracers, trackers or imaging probes in positron emission tomography (PET). Thus, the present invention relates to (i) a compound of formula (I) in which one or more fluorine atoms (or, for example, all fluorine atoms) are 18 replaced by F atoms, (ii) a compound of formula (I) in which one or more carbon atoms (or, for example, all carbon atoms) are 11Compounds of formula (I) in which one or more carbon atoms (or, for example, all carbon atoms) are replaced by C atoms, (iii) one or more nitrogen atoms (or, for example, all nitrogen atoms) are 13 Compounds of formula (I) in which one or more nitrogen atoms (or, for example, all nitrogen atoms) are replaced by N atoms, (iv) one or more oxygen atoms (or, for example, all oxygen atoms) are 15 Compounds of formula (I) in which one or more oxygen atoms (or, for example, all oxygen atoms) are replaced by O atoms, (v) one or more bromine atoms (or, for example, all bromine atoms) are 76 Compounds of formula (I) in which one or more bromine atoms (or, for example, all bromine atoms) are replaced by Br atoms, (vi) one or more bromine atoms (or, for example, all bromine atoms) are 77 Compounds of formula (I) in which one or more bromine atoms (or, for example, all bromine atoms) are replaced by Br atoms, (vii) one or more iodine atoms (or, for example, all iodine atoms) are 120 Compounds of formula (I) in which one or more iodine atoms (or, for example, all iodine atoms) are replaced by I atoms, and (viii) one or more iodine atoms (or, for example, all iodine atoms) are 124 Compounds of formula (I) in which one or more iodine atoms (or, for example, all iodine atoms) are replaced by I atoms. Generally, it is preferred that none of the atoms in the compounds of formula (I) are replaced by a specific isotope.

[0233] The compounds provided herein may be administered as the compound itself or formulated as a medicament. The medicament / pharmaceutical composition may optionally contain one or more pharmaceutically acceptable excipients, such as carriers, diluents, fillers, disintegrants, lubricants, binders, colorants, pigments, stabilizers, preservatives, antioxidants, and / or solubility enhancers.

[0234] The pharmaceutical composition may include one or more solubility enhancers, such as poly(ethylene glycol) having a molecular weight in the range of about 200 to about 5,000 Da (e.g., PEG200, PEG300, PEG400, or PEG600), ethylene glycol, propylene glycol, glycerol, nonionic surfactants, tyloxapol, polysorbate 80, macrogol-15-hydroxystearate (e.g., Kolliphor® HS 15, CAS70142-34-6), 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, dihydroxypropyl-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 thioether, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, vinyl acetate copolymer, vinyl pyrrolidone, sodium lauryl sulfate, sodium dioctyl sulfosuccinate, or any combination thereof, etc.

[0235] The pharmaceutical composition may also contain one or more preservatives, in particular one or more antibacterial preservatives, such as benzyl alcohol, chlorobutanol, 2-ethoxyethanol, m-cresol, chlorocresol (e.g., 2-chloro-3-methyl-phenol or 4-chloro-3-methyl-phenol), benzalkonium chloride, benzethonium chloride, benzoic acid (or a pharmaceutically acceptable salt thereof), sorbic acid (or a pharmaceutically acceptable salt thereof), chlorhexidine, thimerosal, or any combination thereof.

[0236] The pharmaceutical composition 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 composition can be formulated as 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, lozenges, troches, solutions, emulsions, suspensions, syrups, elixirs, powders and granules for reconstitution, dispersible powders and granules, gums, chewable tablets and effervescent tablets. Dosage forms for parenteral administration include solutions, emulsions, suspensions, dispersions and powders and granules for reconstitution. Emulsions are a preferred dosage form for parenteral administration. Dosage forms for rectal and vaginal administration include suppositories and vaginal suppositories. Dosage forms for nasal administration can be administered via inhalation and insufflation, for example, by a metered-dose inhaler. Dosage forms for topical administration include creams, gels, ointments, plasters, patches and transdermal delivery systems.

[0237] The above pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the foregoing constructs, may be administered to a subject by any convenient route of administration including, but not limited to, oral (e.g., as tablets, capsules, or ingestible solutions), topical (e.g., transdermal, intranasal, ocular, buccal, and sublingual), parenteral (e.g., using injection or infusion techniques, e.g., injection, e.g., by subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subepidermal, intraarticular, subarachnoid, or intrasternal injection, e.g., including depot, e.g., by subcutaneous or intramuscular implantation), pulmonary (e.g., by inhalation or insufflation therapy from the mouth or nose, e.g., using an aerosol), gastrointestinal, intrauterine, intraocular, subcutaneous, ophthalmic (including intravitreal or intracameral), rectal, or vaginal administration, whether systemically or locally to a desired site of action.

[0238] When the compound or pharmaceutical composition is administered parenterally, examples of such administration include administering the compound or pharmaceutical composition intravenously, intraarterially, intraperitoneally, intrathecally, intraventricularly, intraurethrally, intrasternal, intracardially, intracranially, intramuscularly or subcutaneously, and / or by using infusion techniques. For parenteral administration, the compound is most preferably used in the form of a sterile aqueous solution which may contain other substances, e.g., salts or glucose sufficient to render the solution isotonic with blood. The aqueous solution should preferably be buffered (preferably to a pH of from 3 to 9) if necessary. The preparation of suitable parenteral formulations under aseptic conditions is readily achieved by standard pharmaceutical techniques well known to those skilled in the art.

[0239] 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.

[0240] The tablets may contain excipients such as microcrystalline cellulose, lactose, sodium citrate, calcium carbonate, calcium hydrogen phosphate and glycine, starch (preferably corn, potato or tapioca starch), disintegrants such as sodium starch glycolate, croscarmellose sodium and certain complex silicates, and granulating binders such as polyvinylpyrrolidone, hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose (HPC), sucrose, gelatin and acacia. Additionally, lubricants such as magnesium stearate, stearic acid, glyceryl behenate and talc may be included. Solid compositions of a similar type may also be used as fillers in gelatin capsules. Preferred excipients in this regard include lactose, starch, cellulose, or high molecular weight polyethylene glycol. For aqueous suspensions and / or elixirs, the drug may be combined with various sweetening or flavoring agents, coloring substances or dyes, emulsifying and / or suspending agents and diluents such as water, ethanol, propylene glycol and glycerin, and combinations thereof.

[0241] For oral administration, the compound or pharmaceutical composition is preferably administered by oral ingestion, particularly by swallowing. Thus, the compound or pharmaceutical composition can be administered to pass through the mouth and into the gastrointestinal tract, which can also be referred to as "oral-gastrointestinal" administration.

[0242] Alternatively, the compound or pharmaceutical composition can be administered in the form of a suppository or pessary, or may be applied topically in the form of a gel, hydrogel, lotion, solution, cream, ointment or spray. The compounds of the present invention may also be administered to the skin or transdermally, for example, by the use of a skin patch.

[0243] The compound or pharmaceutical composition may also be administered by a sustained release system. Suitable examples of sustained release compositions include semipermeable polymer matrices in the form of shaped articles such as films or microcapsules. Sustained release matrices include, for example, polylactide, copolymers of L-glutamic acid and gamma-ethyl-L-glutamate, poly(2-hydroxyethyl methacrylate), ethylene vinyl acetate, or poly-D-(-)-3-hydroxybutyric acid. Sustained release pharmaceutical compositions also include compounds encapsulated in liposomes. Accordingly, the present invention also relates to liposomes containing the compounds of the present invention.

[0244] 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 physiological saline or, preferably, as a solution in isotonic, pH-adjusted, sterile physiological saline, optionally in combination with a preservative such as benzalkonium chloride. Alternatively, they may be formulated as an ointment such as petrolatum.

[0245] It is also contemplated to prepare dry powder formulations of the compounds of formula (I) for pulmonary administration, particularly inhalation. Such dry powder agents may be prepared by spray drying under conditions that result in a substantially amorphous glassy or substantially crystalline bioactive powder. Accordingly, dry powder agents of the compounds of the present invention can be made according to an emulsification / spray drying process.

[0246] For topical application to the skin, the compound or pharmaceutical composition can be formulated as a suitable ointment containing the active compound suspended or dissolved in a mixture with one or more of, for example, the following: mineral oil, liquid petrolatum, white petrolatum, propylene glycol, emulsifying wax, and water. Alternatively, they can be formulated as a suitable lotion or cream containing the active compound suspended or dissolved in a mixture with one or more of, for example, the following: mineral oil, sorbitan monostearate, polyethylene glycol, liquid paraffin, polysorbate 60, cetyl ester wax, 2-octyldodecanol, benzyl alcohol, and water.

[0247] Accordingly, the present invention relates to the compounds or pharmaceutical compositions provided herein, and the corresponding compounds or pharmaceutical compositions are administered by any one of the following routes: oral route; topical routes, such as transdermal, intranasal, ocular, buccal, or sublingual routes; parenteral routes using injection techniques or infusion techniques, such as subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subepidermal, intraarticular, subarachnoid, intrasternal, intraventricular, intraurethral, or intracranial routes; pulmonary routes, such as by inhalation or insufflation therapy; gastrointestinal routes; intrauterine routes; intraocular routes; subcutaneous routes; ophthalmic routes, such as intravitreal or intracameral routes; rectal routes; or vaginal routes. Preferred routes of administration are oral administration or parenteral administration. For each of the compounds or pharmaceutical compositions provided herein, it is particularly preferred that each compound or pharmaceutical composition is administered orally (especially by oral ingestion).

[0248] Typically, 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 may vary and depend on a variety of factors including the activity of the specific compound used, the metabolic stability and duration of action of that compound, age, weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, severity of the particular condition, and the individual subject receiving the therapy.

[0249] The compounds according to the invention are proposed for oral administration to humans (of approximately 70 kg body weight), but non-limiting dosages may be from 0.05 to 2000 mg, preferably from 0.1 mg to 1000 mg of active ingredient per unit dose. The unit dose may be administered, for example, 1 to 3 times per day. The unit dose may also be administered 1 to 7 times per week, for example, at a frequency of less than once per day. It will be appreciated that the dosage may need to be varied routinely according to the age and weight of the patient / subject and the severity of the condition being treated. The exact dosage and further the route of administration will ultimately be at the discretion of the attending physician or veterinarian.

[0250] The pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the foregoing constructs, may be administered in monotherapy (e.g., without co-administering any further therapeutic agent or without co-administering any further therapeutic agent for the same disease treated or prevented by the compound of formula (I)). However, the pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the foregoing constructs, may also be administered in combination with one or more further therapeutic agents. When a compound of formula (I) is used in combination with a second therapeutic agent that is active against the same disease or condition, the dosage of each compound may be different from the dosage when the corresponding compound is used alone, in particular, lower dosages of each compound may be used. The combination of a compound of formula (I) with one or more further therapeutic agents may include simultaneous / concurrent administration (either as a single pharmaceutical formulation or as separate pharmaceutical formulations) of the compound of formula (I) and the further therapeutic agent(s), or sequential / separate administration of the compound of formula (I) and the further therapeutic agent(s). When the administration is sequential, either the compound of formula (I) according to the invention or one or more of the further therapeutic agents may be administered first. When the administration is concurrent, the one or more further therapeutic agents may be included in the same pharmaceutical formulation as the compound of formula (I), or they may be administered as two or more different (separate) pharmaceutical formulations.

[0251] For the treatment or prevention of cancer, one or more additional therapeutic agents administered in combination with the compounds of the present invention are preferably anti-cancer drugs. Anti-cancer drugs administered in combination with a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof include, for example, tumor angiogenesis inhibitors (e.g., protease inhibitors, epidermal growth factor receptor kinase inhibitors, or vascular endothelial growth factor receptor kinase inhibitors); cytotoxic drugs (e.g., antimetabolites, such as purine and pyrimidine analog antimetabolites); antimitotic agents (e.g., microtubule stabilizing agents or antimitotic alkaloids); platinum coordination complexes; antitumor antibiotics; alkylating agents (e.g., nitrogen mustard or nitrosourea); endocrine agents (e.g., corticosteroids, androgens, antiandrogens, estrogens, antiestrogens, aromatase inhibitors, gonadotropin releasing hormone agonists, or somatostatin analogs); compounds that target an enzyme or receptor overexpressed in tumor cells and / or otherwise participate in a specific metabolic pathway that is deregulated (or misregulated) (e.g., ATP and GTP phosphodiesterase inhibitors, histone deacetylase inhibitors, protein kinase inhibitors (serine, threonine and tyrosine kinase inhibitors, such as abelson protein tyrosine kinase inhibitors, etc.) as well as various growth factors, their receptors and corresponding kinase inhibitors (epidermal growth factor receptor kinase inhibitors, vascular endothelial growth factor receptor kinase inhibitors, fibroblast growth factor inhibitors, insulin-like growth factor receptor inhibitors and platelet-derived growth factor receptor kinase inhibitors, etc.)); methionine; aminopeptidase inhibitors; proteasome inhibitors; cyclooxygenase inhibitors (e.g., cyclooxygenase-1 inhibitors or cyclooxygenase-2 inhibitors); topoisomerase inhibitors (e.g., topoisomerase I inhibitors or topoisomerase II inhibitors); poly ADP ribose polymerase inhibitors (PARP inhibitors); epidermal growth factor receptor (EGFR) inhibitors / antagonists; adenosine A 2A receptor antagonist; adenosine A 2B receptor antagonist; dual adenosine A 2A / A 2BIt may be selected from a receptor antagonist; and a prostaglandin E2 receptor 4 (EP4) antagonist.

[0252] Alkylating agents that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, nitrogen mustards (such as cyclophosphamide, mechlorethamine (chloromethine), uracil mustard, melphalan, chlorambucil, ifosfamide, bendamustine, or trofosfamide, etc.), nitrosoureas (such as carmustine, streptozocin, fotemustine, lomustine, nimustine, prednimustine, ranimustine, or semustine, etc.), alkyl sulfonates (such as busulfan, mannosulfan, or treosulfan, etc.), aziridines (such as hexamethylmelamine (altretamine), triethylenemelamine, thiotepa (N,N’N’-triethylenethiophosphoramide), carbocon, or triazicon, etc.), hydrazines (such as procarbazine, etc.), triazenes (such as dacarbazine, etc.), or imidazotetrazines (such as temozolomide, etc.).

[0253] Platinum coordination complexes that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, cisplatin, carboplatin, nedaplatin, oxaliplatin, satraplatin, or triplatin tetranitrate.

[0254] Cytotoxic drugs that can be used as anticancer drugs in combination with the compounds of the present invention may be antimetabolites including, for example, folic acid analog antimetabolites (such as aminopterin, methotrexate, pemetrexed, or raltitrexed, etc.), purine analog antimetabolites (such as cladribine, clofarabine, fludarabine, 6-mercaptopurine (including its prodrug form azathioprine), pentostatin, or 6-thioguanine, etc.), and pyrimidine analog antimetabolites (such as cytarabine, decitabine, 5-fluorouracil (including its prodrug forms capecitabine and tegafur), floxuridine, gemcitabine, enocitabine, or sapacitabine, etc.).

[0255] Antimitotic agents that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, taxanes (such as docetaxel, larotaxel, ortataxel, paclitaxel / taxol, tesetaxel, or nab-paclitaxel (e.g., Abraxane®)), vinca alkaloids (such as vinblastine, vincristine, vinflunine, vindesine, or vinorelbine), epothilones (such as epothilone A, epothilone B, epothilone C, epothilone D, epothilone E, or epothilone F), or epothilone B analogs (such as ixabepilone / azaepothilone B).

[0256] Antitumor antibiotics that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, anthracyclines (such as aclarubicin, daunorubicin, doxorubicin, epirubicin, idarubicin, amrubicin, pirarubicin, valrubicin, or zorubicin), anthraquinones (such as mitoxantrone, or pixantrone), or antitumor antibiotics isolated from Streptomyces (such as actinomycin (including actinomycin D), bleomycin, mitomycin (including mitomycin C), or plicamycin).

[0257] Tyrosine kinase inhibitors that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, axitinib, bosutinib, cediranib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib, sorafenib, sunitinib, axitinib, nintedanib, ponatinib, vandetanib, or bemrafenib.

[0258] Topoisomerase inhibitors that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, topoisomerase I inhibitors (such as irinotecan, topotecan, camptothecin, velotecan, rubitecan, or lamellarin D) or topoisomerase II inhibitors (such as amsacrine, etoposide, etoposide phosphate, teniposide, or doxorubicin).

[0259] PARP inhibitors that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, niraparib, olaparib, rucaparib, talazoparib, veliparib, pamiparib (BGB-290), BMN-673, CEP9722, MK 4827, E7016, or 3-aminobenzamide.

[0260] EGFR inhibitors / antagonists that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, gefitinib, erlotinib, lapatinib, afatinib, neratinib, osimertinib, brigatinib, dacomitinib, vandetanib, pelitinib, canertinib, icotinib, poziotinib, ABT-414, AV-412, PD153035, PKI-166, BMS-690514, CUDC-101, AP26113, XL647, cetuximab, panitumumab, zalutumumab, nimotuzumab, or matuzumab.

[0261] Adenosine A 2A receptor antagonists that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, siporadenant, imaladenant, inupadenant, istradefylline, preladenant, SCH-58261, SCH-442416, ST 1535, or ZM241385.

[0262] Adenosine A 2B receptor antagonists that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, LAS38096 or LAS101057. Dual adenosine A 2A / A 2B receptor antagonists that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, M1069, etomadenant, or INCB106385.

[0263] Prostaglandin E2 receptor 4 (EP4) antagonists that can be used as anticancer drugs in combination with the compounds of the present invention include, for example, DT-9081, grapiprant, palupiprant, BAY-1316957, CJ-42794, ER-819762, GW627368, L-161982, MF498, MF-766, MK-2894, or ONO-AE3-208.

[0264] Additional anticancer drugs may also be used in combination with the compounds of the present invention. Anticancer drugs may include biological or chemical molecules such as TNF-related apoptosis-inducing ligand (TRAIL), tamoxifen, amsacrine, bexarotene, estramustine, ilofibrate, trabectedin, cetuximab, panitumumab, tositumomab, alemtuzumab, bevacizumab, edrecolomab, gemtuzumab, albosidib, seliciclib, aminolevulinic acid, methyl aminolevulinate, efaproxiral, porfimer sodium, talaporfin, temoporfin, verteporfin, alitretinoin, tretinoin, anagrelide, arsenic trioxide, atrasentan, bortezomib, carmofur, celecoxib, dexamethasone, elesclomol, elsamitrucin, etoglucide, lonidamine, lucanthone, masoprocol, mitobronitol, mitoguazone, mitotane, oblimersen, omacetaxine, sitimagene, seladenovec, tegafur, testolactone, thiazofurin, tipifarnib, vorinostat, iniparib, or copanlisib.

[0265] Biological drugs such as antibodies, antibody fragments, antibody constructs (e.g., single-chain constructs), and / or modified antibodies (such as CDR-grafted antibodies, humanized antibodies, "fully human" antibodies, etc.) against cancer or tumor markers / factors / cytokines involved in proliferative diseases can also be used in combination therapy approaches with the compounds of the present invention. Examples of such biomolecules are anti-HER2 antibodies (e.g., trastuzumab, Herceptin®), anti-CD20 antibodies (e.g., rituximab, Rituxan®, MabThera®, Reditux®), anti-CD19 / CD3 constructs, and anti-TNF antibodies (see, e.g., Taylor PC, Curr Opin Pharmacol, 2003, 3(3):323-328).

[0266] Anticancer drugs that can be used in combination with the compounds of the present invention include, in particular, CTLA-4, PD-1, PD-L1, TIGIT, TIM3, LAG3, OX40, CSF1R, IDO, CD40, adenosine A 2A receptor (A2A), adenosine A 2BAn immuno-oncology therapeutic (such as an antibody (e.g., a monoclonal antibody or a polyclonal antibody), an antibody fragment, an antibody construct (e.g., a single-chain construct), or a modified antibody (e.g., a CDR-grafted antibody, a humanized antibody, or a "fully human" antibody) or a small molecule, etc.) that targets any one of the receptors (A2B), A2A / A2B, prostaglandin E2 receptor 4 (EP4), or chemokine (C-C motif) receptor 8 (CCR8) may also be used.Such immuno-oncology therapeutic agents include, for example, anti-CTLA-4 antibodies (e.g., ipilimumab or tremelimumab), anti-PD-1 antibodies (e.g., nivolumab (BMS-936558), pembrolizumab (MK-3475), pidilizumab (CT-011), semipilimab, dostarlimab, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, zimberelimab, AMP-224, AMP-514 (or MEDI0680), JTX-4014, INCMGA00012 (or MGA012), or APE02058), anti-PD-L1 antibodies (e.g., atezolizumab, avelumab, durvalumab, KN035, CK-301, BMS-936559, MEDI4736, MPDL3280A (RG7446), MDX-1105, MEDI6469, or vintafusp alpha), anti-TIGIT antibodies (e.g., tiragolumab, vibostolimab, domvanalimab, etigilimab, BMS-986207, EOS-448, COM902, ASP8374, SEA-TGT, BGB-A1217, IBI-939, or M6223), anti-TIM3 antibodies, anti-LAG3 antibodies (e.g., relatlimab (or BMS-986016), yerramilimab (or LAG525), enserelumab (or TSR-033), tebotelimab (or MGD013), REGN3767 (or R3767), FS118, IMP701, or IMP731), anti-OX40 antibodies (e.g., MEDI0562), anti-CSF1R antibodies (e.g., IMC-CS4 or RG7155), anti-IDO antibodies, anti-CD40 antibodies (e.g., CP-870,893 or Chi Lob 7 / 4), or anti-CCR8 antibodies (e.g., DT-7012, BMS-986340, S-531011, BAY-3375968, GS-1811 (or JTX-1811), FPA157, SRF114, HBM1022, or LM-108).Additional immuno - oncology therapeutics are known in the art, for example, as described in Kyi C et al., FEBS Lett, 2014, 588(2):368 - 76; Intlekofer AM et al., J Leukoc Biol, 2013, 94(1):25 - 39; Callahan MK et al., J Leukoc Biol, 2013, 94(1):41 - 53; Ngiow SF et al., Cancer Res, 2011, 71(21):6567 - 71; and Blattman JN et al., Science, 2004, 305(5681):200 - 5.

[0267] In particular, a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the foregoing constructs, may be administered in combination with an immune checkpoint inhibitor, preferably an antibody (or an antigen-binding fragment thereof, or an antibody construct) against CTLA-4, PD-1, PD-L1, TIGIT, or LAG3. Corresponding preferred examples include any one of ipilimumab or tremelimumab, which are anti-CTLA-4 antibodies; any one of nivolumab, pembrolizumab, pidilizumab, semaprilumab, dostarlimab, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, zimberelimab, AMP-224, AMP-514, JTX-4014, INCMGA00012, or APE02058, which are anti-PD-1 antibodies; any one of atezolizumab, avelumab, durvalumab, KN035, CK-301, BMS-936559, MEDI4736, MPDL3280A, MDX-1105, MEDI6469, or vintafolide alpha, which are anti-PD-L1 antibodies; any one of tirigolumab, vibostolimab, domvanalimab, etigilimab, BMS-986207, EOS-448, COM902, ASP8374, SEA-TGT, BGB-A1217, IBI-939, or M6223, which are anti-TIGIT antibodies; and / or any one of relatlimab, yerramilimab, enserelumab, tebotelimab, REGN3767, FS118, IMP701, or IMP731, which are anti-LAG3 antibodies, but are not limited thereto.Accordingly, the present invention relates to a pharmaceutical composition for use in the treatment or prevention of cancer, comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the foregoing constructs, optionally in combination with a pharmaceutically acceptable excipient, wherein the compound or the pharmaceutical composition is administered in combination with one or more immune checkpoint inhibitors, and the one or more immune checkpoint inhibitors are preferably selected from anti-CTLA-4 antibodies, anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-TIGIT antibodies, and / or anti-LAG3 antibodies (for example, the one or more immune checkpoint inhibitors may be selected from anti-CTLA-4 antibodies, anti-PD-1 antibodies and / or anti-PD-L1 antibodies, such as ipilimumab, tremelimumab, nivolumab, pembrolizumab, semipilimab, spartalizumab, camrelizumab, sintilimab, tislelizumab, AMP-224, AMP-514, atezolizumab, avelumab, durvalumab, KN035, or CK-301, etc.), more preferably, the one or more immune checkpoint inhibitors are selected from ipilimumab, tremelimumab, nivolumab, pembrolizumab, pidilizumab, semipilimab, dostarlimab, spartalizumab, camrelizumab, sintilimab, tislelizumab, tripalimumab, dimberelimab, AMP-224, AMP-514, JTX-4014, INCMGA00012, APE02058, atezolizumab, avelumab, durvalumab, KN035, CK-301, BMS-936559, MEDI4736, MPDL3280A, MDX-1105, MEDI6469, vindraluspa alpha, tirigolumab, vibostrimumab, domvanalimab, etigilimab, BMS-986207, EOS-448, COM902, ASP8374, SEA-TGT, BGB-A1217, IBI-939, M6223, relatlimab, yerramilimab, enserlimab, tebotelimab, REGN3767, FS118, IMP701, and IMP731.

[0268] Furthermore, the pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the aforementioned constructs may also be administered in combination with an anti-CCR8 antibody (particularly an antagonist anti-CCR8 antibody), for example, DT-7012, BMS-986340, S-531011, BAY-3375968, GS-1811 (or JTX-1811), FPA157, SRF114, HBM1022, or LM-108. Accordingly, the present invention relates to a pharmaceutical composition for use in the treatment or prevention of cancer, comprising the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the aforementioned constructs, optionally in combination with a pharmaceutically acceptable excipient, wherein the compound or the pharmaceutical composition is administered in combination with one or more anti-CCR8 antibodies (which may be selected from, for example, DT-7012, BMS-986340, S-531011, BAY-3375968, GS-1811 (or JTX-1811), FPA157, SRF114, HBM1022, and LM-108).

[0269] Accordingly, the present invention particularly relates to a pharmaceutical composition for use in the treatment or prevention of cancer, comprising the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any of the aforementioned constructs, optionally in combination with a pharmaceutically acceptable excipient, wherein the compound or the pharmaceutical composition is administered in combination with one or more anti-cancer drugs (comprising any one or more of the specific anti-cancer drugs described above herein).

[0270] The combinations referred to above may conveniently be provided for use in the form of pharmaceutical formulations. The individual components of such combinations may be administered sequentially or simultaneously / combinatorially, either separately or in combined pharmaceutical formulations, by any convenient route. When the administration is sequential, either the compound of the invention (i.e., a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof) or a further therapeutic agent may be administered first. When the administration is simultaneous, the combination may be administered either as the same pharmaceutical composition or as different pharmaceutical compositions. It will be appreciated that when combined in the same formulation, two or more compounds must be stable and compatible with each other and with the other components of the formulation. When formulated separately, they may be provided as any convenient formulation and administered by any convenient route. For the combinations described above, it is preferred that the individual components of such combinations be provided as separate pharmaceutical formulations.

[0271] The subject or patient to be treated according to the invention may 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., a human male or female) or a non-human mammal (e.g., a guinea pig, hamster, rat, mouse, rabbit, dog, cat, horse, monkey, ape, marmoset, baboon, gorilla, chimpanzee, orangutan, langur, sheep, cow, or pig, etc.). Most preferably, the subject / patient to be treated according to the invention is a human.

[0272] The term "treatment" of a disorder or disease as used herein is well known in the art. "Treatment" of a disorder or disease implies that the disorder or disease is suspected or diagnosed in a patient / subject. A patient / subject suspected of suffering from a disorder or disease typically exhibits certain clinica...

Claims

1. Compounds of the following formula (I) 【Chemistry 1】 [In the formula, Ring B is condensed with ring D and contains non-aromatic C ４～８ It is a carbocyclic ring or a non-aromatic 4-8 membered heterocyclic ring. The carbocyclic ring or the heterocyclic ring is (i) group R １ (ii) The group R is substituted and bonded to the same ring carbon atom of the carbocyclic ring or the heterocyclic ring. ２Ａ and R ２Ｂ It is replaced by (iii) one or more base R Ｙ It may also be replaced with Ring D is a 5 or 6-membered aromatic heterocycle fused to ring B, the aromatic heterocycle contains at least one nitrogen ring atom, the aromatic heterocycle is substituted with the group -L-A, and the aromatic heterocycle contains one or more groups R Ｘ It may also be replaced with R １ is selected from C １～５ alkyl, C ２～５ alkenyl, C ２～５ alkynyl, -(C ０～５ alkylene)-carbocyclic, and -(C ０～５ alkylene)-heterocyclic, The alkyl, the alkenyl, the alkynyl, the -(C ０～５ Alkylene) - Alkylene group in carbocykyl, and the - (C ０～５ The alkylene groups in the alkylene-heterocyclyl are each one or more groups R １２ The alkyl, the alkenyl, the alkynyl, and the -(C) may be substituted. ０～５ Alkylene) - Alkylene group in carbocykyl, or the aforementioned - (C ０～５ One or more -CH groups contained in the alkylene group of an alkylene-heterocyclyl ２ - The units are -C (R) respectively. Ｌ１ ) (Caution Ｌ１ )-, -O-, -S-, -SO-, -SO ２ -, -CO-, and -N(R Ｌ１ ) - may be replaced by a group independently selected from each R Ｌ１ These are, independently, hydrogen or C １～５ It is an alkyl group, and two R groups are bonded to the same carbon atom. Ｌ１ They may also bond to each other and, together with the carbon atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group. Said -(C ０～５ Alkylene)-Carbocyclyl group in carbocyclyl and the aforementioned-(C ０～５ Each heterocyclyl group in an alkylene-heterocyclyl is one or more R groups. １１ It may also be replaced with Each R １１ C １～５ Alkyl, C ２～５ Alkenil, C ２～５ Alkinyl, -(C ０～３ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-O(C) １～５ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkylene)-S(C) １～５ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkilen)-NH ２ , - (C ０～３ Alkylene)-NH(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkylene)-NH-OH,-(C ０～３ Alkylene)-N(C) １～５ Alkyl)-OH,-(C ０～３ Alkylene)-NH-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-O(C １～５ Alkyl), -(C ０～３ Alkylene)-halogen,-(C) ０～３ Alkylene) - (C １～５ Haloalkyl), -(C ０～３ Alkylene)-O-(C) １～５ Haloalkyl), -(C ０～３ Alkylene)-CN,-(C ０～３ Alkylene)-CHO,-(C) ０～３ Alkylene)-CO-(C) １～５ alkyl), -(C ０～３ alkylene)-COOH, -(C ０～３ alkylene)-CO-O-(C １～５ alkyl), -(C ０～３ alkylene)-O-CO-(C １～５ alkyl), -(C ０～３ alkylene)-CO-NH ２ , -(C ０～３ alkylene)-CO-NH(C １～５ alkyl), -(C ０～３ alkylene)-CO-N(C １～５ alkyl)(C １～５ alkyl), -(C ０～３ alkylene)-NH-CO-(C １～５ alkyl), -(C ０～３ alkylene)-N(C １～５ alkyl)-CO-(C １～５ alkyl), -(C ０～３ alkylene)-NH-COO(C １～５ alkyl), -(C ０～３ alkylene)-N(C １～５ alkyl)-COO(C １～５ alkyl), -(C ０～３ alkylene)-O-CO-NH(C １～５ alkyl), -(C ０～３ alkylene)-O-CO-N(C １～５ alkyl)(C １～５ alkyl), -(C ０～３ alkylene)-SO ２ -NH ２ , -(C ０～３ alkylene)-SO ２ -NH(C １～５ alkyl), -(C ０～３ alkylene)-SO ２ -N(C １～５ alkyl)(C １～５ alkyl), -(C ０～３ alkylene)-NH-SO ２ -(C １～５ alkyl), -(C ０～３ alkylene)-N(C １～５ alkyl)-SO ２ -(C １～５ Alkyl), -(C ０～３ Alkylene)-SO-(C １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ - (C １～５ Alkyl), -(C ０～３ Alkilen)-Carbocyclyl,-(C) ０～３ Alkilen)-heterocyclyl and -L Ｚ -R Ｚ Selected independently from, and the above-(C ０～３ Alkylene)-Carbocyclyl group in carbocyclyl and the aforementioned-(C ０～３ Each heterocyclyl group in an alkylene-heterocyclyl is one or more R groups. Ｃｙｃ It may also be replaced with Each R １２ is -OH, -O(C) １～５ Alkyl), -O (C １～５ Alkylene)-OH,-O(C) １～５ Alkylene)-O(C) １～５ Alkyl), -SH, -S(C １～５ Alkyl), -S (C １～５ Alkylene)-SH,-S(C) １～５ Alkylene)-S(C) １～５ Alkyl), -NH ２ ,-NH(C １～５ Alkyl), -N(C １～５ (Alkyl) (C １～５ Alkyl), -NH-OH, -N(C １～５ Alkyl)-OH,-NH-O(C １～５ Alkyl), -N(C １～５ Alkyl)-O(C １～５ Alkyl), halogen, C １～５ Haloalkyl, -O-(C) １～５ Haloalkyl), -CN, -CHO, -CO-(C) １～５ Alkyl), -COOH, -CO-O-(C １～５ Alkyl), -O-CO-(C １～５ Alkyl), -CO-NH ２ ,-CO-NH(C １～５ Alkyl), -CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -NH-CO-(C １～５ Alkyl), -N(C １～５ Alkyl)-CO-(C １～５ Alkyl), -NH-COO(C １～５ Alkyl), -N(C １～５ Alkyl)-COO(C １～５ Alkyl), -O-CO-NH(C １～５ Alkyl), -O-CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -SO ２ -NH ２ , -SO ２ -NH(C) １～５ Alkyl), -SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -NH-SO ２ - (C １～５ Alkyl), -N(C １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -SO-(C １～５ Alkyl), -SO ２ - (C １～５ Alkyl), carbocyrillic, heterocyclyl, and -L Ｚ -R Ｚ Independently selected from, the carbocyclyl and heterocyclyl each have one or more R groups Ｃｙｃ It may also be replaced with R ２Ａ and R ２Ｂ These elements bond to each other, and together with the carbon atoms to which they are bonded, form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, and the cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl has one or more R groups. ２１ Is it okay if it is replaced with? or R ２Ａ and R ２Ｂ C １～５ Alkyl, C ２～５ Alkenil, C ２～５ Alkinyl, -(C ０～５ Alkilen)-Carbocyclyl, and-(C ０～５ Each is independently selected from alkylene-heterocyclyl, and the alkyl, alkenyl, alkynyl, and -(C ０～５ Alkylene) - Alkylene group in carbocykyl, and the - (C ０～５ The alkylene groups in the alkylene-heterocyclyl are each one or more groups R ２２ The alkyl, the alkenyl, the alkynyl, and the -(C) may be substituted. ０～５ Alkylene) - Alkylene group in carbocykyl, or the aforementioned - (C ０～５ One or more -CH groups contained in the alkylene group of an alkylene-heterocyclyl ２ The units are -O-, -NH-, and -N(C) respectively. １～５ Alkyl)-, -CO-, -S-, -SO-, and -SO ２ - may be replaced by a base selected independently of - (C ０～５ Alkylene)-Carbocyclyl group in carbocyclyl and the aforementioned-(C ０～５ Each heterocyclyl group in an alkylene-heterocyclyl is one or more R groups. Ｃｙｃ It may also be replaced with R ２Ａ and base R Ｙ They may also bond to each other and, together with the ring atoms to which they are bonded, form a carbocykryl or heterocyclyl, wherein the carbocykryl or heterocyclyl comprises one or more groups R Ｃｙｃ It may also be replaced with Each R ２１ C １～５ Alkyl, C ２～５ Alkenil, C ２～５ Alkinyl, -(C ０～３ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-O(C) １～５ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkylene)-S(C) １～５ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkilen)-NH ２ , - (C ０～３ Alkylene)-NH(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkylene)-NH-OH,-(C ０～３ Alkylene)-N(C) １～５ Alkyl)-OH,-(C ０～３ Alkylene)-NH-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-O(C １～５ Alkyl), -(C ０～３ Alkylene)-halogen,-(C) ０～３ Alkylene) - (C １～５ Haloalkyl), -(C ０～３ Alkylene)-O-(C) １～５ Haloalkyl), -(C ０～３ Alkylene)-CN,-(C ０～３ Alkylene)-CHO,-(C) ０～３ Alkylene)-CO-(C) １～５ Alkyl), -(C ０～３ Alkylene)-COOH,-(C ０～３ Alkylene)-CO-O-(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-(C １～５ Alkyl), -(C ０～３ Alkilen)-CO-NH ２ , - (C ０～３ Alkylene)-CO-NH(C １～５ Alkyl), -(C ０～３ Alkylene)-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkilen)-NH-CO-(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-CO-(C １～５ Alkyl), -(C ０～３ Alkilen)-NH-COO(C １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-COO(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-NH(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ -NH ２ , - (C ０～３ Alkylene)-SO ２ -NH(C) １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkilen)-NH-SO4 ２ - (C １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -(C ０～３ Alkylene)-SO-(C １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ - (C １～５ Alkyl), -(C ０～３ Alkilen)-Carbocyclyl,-(C) ０～３ Alkilen)-heterocyclyl and -L Ｚ -R Ｚ Selected independently from, and the above-(C ０～３ Alkylene)-Carbocyclyl group in carbocyclyl and the aforementioned-(C ０～３ Each heterocyclyl group in an alkylene-heterocyclyl is one or more R groups. Ｃｙｃ It may also be replaced with Each R ２２ is -OH, -O(C) １～５ Alkyl), -O (C １～５ Alkylene)-OH,-O(C) １～５ Alkylene)-O(C) １～５ Alkyl), -SH, -S(C １～５ Alkyl), -S (C １～５ Alkylene)-SH,-S(C) １～５ Alkylene)-S(C) １～５ Alkyl), -NH ２ ,-NH(C １～５ Alkyl), -N(C １～５ (Alkyl) (C １～５ Alkyl), -NH-OH, -N(C １～５ Alkyl)-OH,-NH-O(C １～５ Alkyl), -N(C １～５ Alkyl)-O(C １～５ Alkyl), halogen, C １～５ Haloalkyl, -O-(C) １～５ Haloalkyl), -CN, -CHO, -CO-(C) １～５ Alkyl), -COOH, -CO-O-(C １～５ Alkyl), -O-CO-(C １～５ Alkyl), -CO-NH ２ ,-CO-NH(C １～５ Alkyl), -CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -NH-CO-(C １～５ Alkyl), -N(C １～５ Alkyl)-CO-(C １～５ Alkyl), -NH-COO(C １～５ Alkyl), -N(C １～５ Alkyl)-COO(C １～５ Alkyl), -O-CO-NH(C １～５ Alkyl), -O-CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -SO ２ -NH ２ , -SO ２ -NH(C) １～５ Alkyl), -SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -NH-SO ２ - (C １～５ Alkyl), -N(C １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -SO-(C １～５ Alkyl), -SO ２ - (C １～５ Alkyl), carbocyrillic, heterocyclyl, and -L Ｚ -R Ｚ Independently selected from, the carbocyclyl and heterocyclyl each have one or more R groups Ｃｙｃ It may also be replaced with Each R Ｘ C １～５ Alkyl, C ２～５ Alkenil, C ２～５ Alkinyl, -(C ０～３ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-O(C) １～５ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkylene)-S(C) １～５ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkilen)-NH ２ , - (C ０～３ Alkylene)-NH(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkylene)-NH-OH,-(C ０～３ Alkylene)-N(C) １～５ Alkyl)-OH,-(C ０～３ Alkylene)-NH-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-O(C １～５ Alkyl), -(C ０～３ Alkylene)-halogen,-(C) ０～３ Alkylene) - (C １～５ Haloalkyl), -(C ０～３ Alkylene)-O-(C) １～５ Haloalkyl), -(C ０～３ Alkylene)-CN,-(C ０～３ Alkylene)-CHO,-(C) ０～３ Alkylene)-CO-(C) １～５ Alkyl), -(C ０～３ Alkylene)-COOH,-(C ０～３ Alkylene)-CO-O-(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-(C １～５ Alkyl), -(C ０～３ Alkilen)-CO-NH ２ , - (C ０～３ Alkylene)-CO-NH(C １～５ Alkyl), -(C ０～３ Alkylene)-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkilen)-NH-CO-(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-CO-(C １～５ Alkyl), -(C ０～３ Alkilen)-NH-COO(C １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-COO(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-NH(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ -NH ２ , - (C ０～３ Alkylene)-SO ２ -NH(C) １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkilen)-NH-SO4 ２ - (C １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -(C ０～３ Alkylene)-SO-(C １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ - (C １～５ Alkyl), -(C ０～３ Alkilen)-Carbocyclyl,-(C) ０～３ Alkilen)-heterocyclyl and -L Ｚ -R Ｚ Selected independently from, and the above-(C ０～３ Alkylene)-Carbocyclyl group in carbocyclyl and the aforementioned-(C ０～３ Each heterocyclyl group in an alkylene-heterocyclyl is one or more R groups. Ｃｙｃ It may also be replaced with Each R Ｙ C １～５ Alkyl, C ２～５ Alkenil, C ２～５ Alkinyl, -(C ０～３ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-O(C) １～５ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkylene)-S(C) １～５ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkilen)-NH ２ , - (C ０～３ Alkylene)-NH(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkylene)-NH-OH,-(C ０～３ Alkylene)-N(C) １～５ Alkyl)-OH,-(C ０～３ Alkylene)-NH-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-O(C １～５ Alkyl), -(C ０～３ Alkylene)-halogen,-(C) ０～３ Alkylene) - (C １～５ Haloalkyl), -(C ０～３ Alkylene)-O-(C) １～５ Haloalkyl), -(C ０～３ Alkylene)-CN,-(C ０～３ Alkylene)-CHO,-(C) ０～３ Alkylene)-CO-(C) １～５ Alkyl), -(C ０～３ Alkylene)-COOH,-(C ０～３ Alkylene)-CO-O-(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-(C １～５ Alkyl), -(C ０～３ Alkilen)-CO-NH ２ , - (C ０～３ Alkylene)-CO-NH(C １～５ Alkyl), -(C ０～３ Alkylene)-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkilen)-NH-CO-(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-CO-(C １～５ Alkyl), -(C ０～３ Alkilen)-NH-COO(C １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-COO(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-NH(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ -NH ２ , - (C ０～３ Alkylene)-SO ２ -NH(C) １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkilen)-NH-SO4 ２ - (C １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -(C ０～３ Alkylene)-SO-(C １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ - (C １～５ Alkyl), -(C ０～３ Alkilen)-Carbocyclyl,-(C) ０～３ Alkilen)-heterocyclyl and -L Ｚ -R Ｚ Selected independently from, and the above-(C ０～３ Alkylene)-Carbocyclyl group in carbocyclyl and the aforementioned-(C ０～３ Each heterocyclyl group in an alkylene-heterocyclyl is one or more R groups. Ｃｙｃ It may also be replaced with Any two groups R bonded to the same ring carbon atom Ｙ (i) They may also bond to each other and together with the carbon atoms to which they are bonded to form a cycloalkyl or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is one or more groups R Ｃｙｃ They may be substituted with, or (ii) they may form a base = O with each other. L is -CO-, -SO-, and -SO ２ - Selected from, Base A is -N(-R Ｎ )-R Ｎ Alternatively, it is a heterocycline, the heterocycline being bonded to group L via a ring nitrogen atom, and the heterocycline being one or more groups R Ａ It may also be replaced with Each R Ｎ is hydrogen, C １～８ Alkyl, C ２～８ Alkenil, C ２～８ Alkinyl, -(C ０～８ Alkylene)-OH,-(C) ０～８ Alkylene)-O(C) １～５ Alkyl), -(C ０～８ Alkylene)-SH,-(C ０～８ Alkylene)-S(C) １～５ Alkyl), -(C １～８ Alkilen)-NH ２ , - (C １～８ Alkylene)-NH(C) １～５ Alkyl), -(C １～８ Alkylene)-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C １～８ Alkylene)-halogen,-(C) １～８ Alkylene)-C １～５ Haloalkyl, -(C) ０～８ Alkylene)-O-(C) １～８ Haloalkyl), -(C ０～８ Alkylene)-CN,-(C ０～８ Alkylene)-CHO,-(C) ０～８ Alkylene)-CO-(C) １～５ Alkyl), -(C ０～８ Alkylene)-COOH,-(C ０～８ Alkylene)-CO-O-(C １～５ Alkyl), -(C ０～８ Alkylene)-O-CO-(C １～５ Alkyl), -(C ０～８ Alkilen)-CO-NH ２ , - (C ０～８ Alkylene)-CO-NH(C １～５ Alkyl), -(C ０～８ Alkylene)-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C １～８ Alkilen)-NH-CO-(C) １～５ Alkyl), -(C １～８ Alkylene)-N(C) １～５ Alkyl)-CO-(C １～５ Alkyl), -(C １～８ Alkilen)-NH-COO(C １～５ Alkyl), -(C １～８ Alkylene)-N(C) １～５ Alkyl)-COO(C １～５ Alkyl), -(C ０～８ Alkylene)-O-CO-NH(C １～５ Alkyl), -(C ０～８ Alkylene)-O-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～８ Alkylene)-SO ２ -NH ２ , - (C ０～８ Alkylene)-SO ２ -NH(C) １～５ Alkyl), -(C ０～８ Alkylene)-SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C １～８ Alkilen)-NH-SO4 ２ - (C １～５ Alkyl), -(C １～８ Alkylene)-N(C) １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -(C ０～８ Alkylene)-SO-(C １～５ Alkyl), -(C ０～８ Alkylene)-SO ２ - (C １～５ Alkyl), -(C ０～８ Alkilen)-Carbocyclyl, and-(C ０～８ Independently selected from alkylene-heterocyclines, the C １～８ alkyl, the C ２～８ Alkenyl, the C ２～８ Alkinyl, as well as the aforementioned C ０～８ Alkylene and C １～８ One or more -CH groups are contained within any of the alkylene groups. ２ The units are -O-, -NH-, and -N(C) respectively. １～５ Alkyl)-, -CO-, -S-, -SO-, and -SO ２ - may be replaced by a base selected independently of - (C ０～８ Alkylene)-Carbocyclyl group in carbocyclyl and the aforementioned-(C ０～８ Each heterocyclyl group in an alkylene-heterocyclyl is one or more R groups. Ｃｙｃ It may be substituted with at least one base R Ｎ It is not hydrogen, Each R Ａ C １～５ Alkyl, C ２～５ Alkenil, C ２～５ Alkinyl, -(C ０～３ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-O(C) １～５ Alkylene)-OH,-(C) ０～３ Alkylene)-O(C) １～５ Alkylene)-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkylene)-S(C) １～５ Alkylene)-SH,-(C ０～３ Alkylene)-S(C) １～５ Alkylene)-S(C) １～５ Alkyl), -(C ０～３ Alkilen)-NH ２ , - (C ０～３ Alkylene)-NH(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkylene)-NH-OH,-(C ０～３ Alkylene)-N(C) １～５ Alkyl)-OH,-(C ０～３ Alkylene)-NH-O(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-O(C １～５ Alkyl), -(C ０～３ Alkylene)-halogen,-(C) ０～３ Alkylene) - (C １～５ Haloalkyl), -(C ０～３ Alkylene)-O-(C) １～５ Haloalkyl), -(C ０～３ Alkylene)-CN,-(C ０～３ Alkylene)-CHO,-(C) ０～３ Alkylene)-CO-(C) １～５ Alkyl), -(C ０～３ Alkylene)-COOH,-(C ０～３ Alkylene)-CO-O-(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-(C １～５ Alkyl), -(C ０～３ Alkilen)-CO-NH ２ , - (C ０～３ Alkylene)-CO-NH(C １～５ Alkyl), -(C ０～３ Alkylene)-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkilen)-NH-CO-(C) １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-CO-(C １～５ Alkyl), -(C ０～３ Alkilen)-NH-COO(C １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-COO(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-NH(C １～５ Alkyl), -(C ０～３ Alkylene)-O-CO-N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ -NH ２ , - (C ０～３ Alkylene)-SO ２ -NH(C) １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -(C ０～３ Alkilen)-NH-SO4 ２ - (C １～５ Alkyl), -(C ０～３ Alkylene)-N(C) １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -(C ０～３ Alkylene)-SO-(C １～５ Alkyl), -(C ０～３ Alkylene)-SO ２ - (C １～５ Alkyl), -(C ０～３ Alkilen)-Carbocyclyl,-(C) ０～３ Alkilen)-heterocyclyl and -L Ｚ -R Ｚ Selected independently from, and the above-(C ０～３ Alkylene)-Carbocyclyl group in carbocyclyl and the aforementioned-(C ０～３ Each heterocyclyl group in an alkylene-heterocyclyl is one or more R groups. Ｃｙｃ It may also be substituted with any two groups R bonded to the same carbon atom of group A. Ａ They may also bond to each other and, together with the carbon atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, the cycloalkyl or heterocycloalkyl group comprising one or more R groups Ｃｙｃ It may also be replaced with Each R Ｃｙｃ C １～５ Alkyl, C ２～５ Alkenil, C ２～５ Alkinyl, -OH, -O(C) １～５ Alkyl), -O (C １～５ Alkylene)-OH,-O(C) １～５ Alkylene)-O(C) １～５ Alkyl), -SH, -S(C １～５ Alkyl), -S (C １～５ Alkylene)-SH,-S(C) １～５ Alkylene)-S(C) １～５ Alkyl), -NH ２ ,-NH(C １～５ Alkyl), -N(C １～５ (Alkyl) (C １～５ Alkyl), -NH-OH, -N(C １～５ Alkyl)-OH,-NH-O(C １～５ Alkyl), -N(C １～５ Alkyl)-O(C １～５ Alkyl), halogen, C １～５ Haloalkyl, -O-(C) １～５ Haloalkyl), -CN, -CHO, -CO(C) １～５ Alkyl), -COOH, -COO(C １～５ Alkyl), -O-CO(C １～５ Alkyl), -CO-NH ２ ,-CO-NH(C １～５ Alkyl), -CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -NH-CO(C １～５ Alkyl), -N(C １～５ Alkyl)-CO(C １～５ Alkyl), -NH-COO(C １～５ Alkyl), -N(C １～５ Alkyl)-COO(C １～５ Alkyl), -O-CO-NH(C １～５ Alkyl), -O-CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -SO ２ -NH ２ , -SO ２ -NH(C) １～５ Alkyl), -SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -NH-SO ２ - (C １～５ Alkyl), -N(C １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -SO ２ - (C １～５ Alkyl), -SO-(C １～５ Alkyl), -P(=O)(-OH)(-OH), -P(=O)(-OH)(-O-C １～５ Alkyl), -P (=O) (-O-C) １～５ Alkyl) (-O-C) １～５ Alkyl), -(C ０～３ Alkylene)-cycloalkyl,-(C) ０～３ Alkylene)-heterocycloalkyl, and -L Ｚ -R Ｚ Selected independently from, Each L Ｚ Covalent bond, C １～７ Alkylene, C ２～７ Alkenylene and C ２～７ Independently selected from alkylene, the alkylene, the alkenylene and the alkenylene are each halogen, C １～５ Haloalkyl, -O-(C) １～５ Haloalkyl), -CN, -OH, -O(C １～５ Alkyl), -SH, -S(C １～５ Alkyl), -NH ２ ,-NH(C １～５ Alkyl), and -N(C １～５ (Alkyl) (C １～５ The alkylene may be substituted with one or more groups independently selected from alkyl groups, and furthermore, one or more -CH groups contained in the alkylene, alkenylene, or alkynylene. ２ The units are -O-, -NH-, and -N(C) respectively. １～５ Alkyl)-, -CO-, -S-, -SO-, and -SO ２ - may be replaced by a base selected independently of it, Each R Ｚ is -OH, -O(C) １～５ Alkyl), -O (C １～５ Alkylene)-OH,-O(C) １～５ Alkylene)-O(C) １～５ Alkyl), -SH, -S(C １～５ Alkyl), -S (C １～５ Alkylene)-SH,-S(C) １～５ Alkylene)-S(C) １～５ Alkyl), -NH ２ ,-NH(C １～５ Alkyl), -N(C １～５ (Alkyl) (C １～５ Alkyl), -NH-OH, -N(C １～５ Alkyl)-OH,-NH-O(C １～５ Alkyl), -N(C １～５ Alkyl)-O(C １～５ Alkyl), halogen, C １～５ Haloalkyl, -O-(C) １～５ Haloalkyl), -CN, -CHO, -CO(C) １～５ Alkyl), -COOH, -COO(C １～５ Alkyl), -O-CO(C １～５ Alkyl), -CO-NH ２ ,-CO-NH(C １～５ Alkyl), -CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -NH-CO(C １～５ Alkyl), -N(C １～５ Alkyl)-CO(C １～５ Alkyl), -NH-COO(C １～５ Alkyl), -N(C １～５ Alkyl)-COO(C １～５ Alkyl), -O-CO-NH(C １～５ Alkyl), -O-CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -SO ２ -NH ２ , -SO ２ -NH(C) １～５ Alkyl), -SO ２ -N(C) １～５ (Alkyl) (C １～５ -NH-SO (alkyl), ２ -(C １～５ alkyl), -N(C １～５ alkyl)-SO ２ -(C １～５ alkyl), -SO ２ -(C １～５ alkyl), -SO-(C １～５ alkyl), aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each independently selected from C １～５ alkyl, C ２～５ alkenyl, C ２～５ alkynyl, halogen, C １～５ haloalkyl, -O-(C １～５ haloalkyl), -CN, -OH, -O(C １～５ alkyl), -SH, -S(C １～５ alkyl), -NH ２ , -NH(C １～５ alkyl), -N(C １～５ alkyl)(C １～５ alkyl), -CHO, -CO-(C １～５ alkyl), -COOH, -CO-O-(C １～５ alkyl), -O-CO-(C １～５ alkyl), -CO-NH ２ , -CO-NH(C １～５ alkyl), -CO-N(C １～５ alkyl)(C １～５ alkyl), -NH-CO-(C １～５ alkyl), -N(C １～５ alkyl)-CO-(C １～５ alkyl), -NH-COO(C １～５ alkyl), -N(C １～５ alkyl)-COO(C １～５ alkyl), -O-CO-NH(C １～５ alkyl), -O-CO-N(C １～５ alkyl)(C １～５ alkyl), -SO ２ -NH ２ , -SO ２ -NH(C １～５ alkyl), -SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -NH-SO ２ - (C １～５ Alkyl), -N(C １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -SO-(C １～５ Alkyl), -SO ２ - (C １～５ The groups may be substituted with one or more groups independently selected from alkyl, carbocyrill, and heterocyclyl groups, wherein the carbocyrill and heterocyclyl groups are each C １～５ Alkyl, C ２～５ Alkenil, C ２～５ Alkynyl, halogen, C １～５ Haloalkyl, -O-(C) １～５ Haloalkyl), -CN, -OH, -O(C １～５ Alkyl), -SH, -S(C １～５ Alkyl), -NH ２ ,-NH(C １～５ Alkyl), -N(C １～５ (Alkyl) (C １～５ Alkyl), -CHO, -CO- (C １～５ Alkyl), -COOH, -CO-O-(C １～５ Alkyl), -O-CO-(C １～５ Alkyl), -CO-NH ２ ,-CO-NH(C １～５ Alkyl), -CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -NH-CO-(C １～５ Alkyl), -N(C １～５ Alkyl)-CO-(C １～５ Alkyl), -NH-COO(C １～５ Alkyl), -N(C １～５ Alkyl)-COO(C １～５ Alkyl), -O-CO-NH(C １～５ Alkyl), -O-CO-N(C １～５ (Alkyl) (C １～５ Alkyl), -SO ２ -NH ２ , -SO ２ -NH(C) １～５ Alkyl), -SO ２ -N(C) １～５ (Alkyl) (C １～５ Alkyl), -NH-SO ２ - (C １～５ Alkyl), -N(C １～５ Alkyl)-SO ２ - (C １～５ Alkyl), -SO-(C １～５ Alkyl), and -SO ２ - (C １～５ It may be substituted with one or more groups independently selected from alkyl groups, however, - Ring B is a pyrrolidinyl ring, and ring D is a pyridinyl ring, R ２Ａ and R ２Ｂ When these groups bond to each other and together with the carbon atoms to which they are bonded, they form a cyclopropyl group, and L is -CO- and group A is morpholine-4-yl, R １ 5-R １１ -Pyrimidine-2-yl or acetyl, - ring B and ring D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl ring, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-c]pyridinyl ring or 6-oxo-6,7-dihydro-5H-pyrrolo[2,3-c]pyridazinyl ring, R ２Ａ and R ２Ｂ are each methyl, R １ is phenyl which may be substituted with one or more groups R １１ , L is -CO-, and when the group A is -NH-R Ｎ , R Ｎ is not a heterocycloalkyl containing one oxidized sulfur ring atom and all other ring atoms being carbon atoms and being substituted with a methyl group - Rings B and D combine to form 3-R Ｘ It is a -4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyradinyl ring, R Ｘ is -OH, and R ２Ａ and R ２Ｂ One of them is methyl, R ２Ａ and R ２Ｂ One of the other is -CON(-CH ３ ) ２ And R １ The first group is methyl, L is -CO-, and group A is -NH-R Ｎ If R Ｎ It is not 4-fluorobenzyl, - Rings B and D together form a 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine ring, a 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine ring, or a 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine ring, L is -CO-, and group A is -NH-R Ｎ And R １ ga-CH ２ -phenyl or -CH ２ -Pyridinyl, and the aforementioned -CH ２ - Phenyl in phenyl and the aforementioned -CH ２ - Each pyridinyl in the pyridinyl has one or more R groups １１ If it is acceptable to substitute with R ２Ａ and R ２Ｂ [provided that it is not methyl] or a pharmaceutically acceptable salt or solvate thereof.

2. Ring B is a pyrrolidinyl ring or a piperidinyl ring, and the pyrrolidinyl ring or piperidinyl ring has one or more groups R Ｙ It may also be substituted with base R １ The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is bonded to the nitrogen ring atom of the pyrrolidinyl ring or the piperidinyl ring.

3. Ring B has one or two bases R Ｙ The following expressions may be substituted with: 【Chemistry 2】 The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

4. Ring D is a six-membered aromatic heterocycle containing one or two nitrogen ring atoms, but all the remaining ring atoms are carbon atoms, and the aromatic heterocycle contains one or more groups R Ｘ The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, which may be substituted with.

5. Ring D is a pyridinyl ring or a pyrazinyl ring, and the pyridinyl ring or the pyrazinyl ring has one or more groups R Ｘ The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, which may be substituted with.

6. The compound of formula (I) has the following structure: 【Transformation 3】 A compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, having the above.

7. R １ However, -L １ -Carbocyclyl or -L １ - is a heterocyclyl, and the above-L １ -Carbocyclyl in carbocyclyl or the aforementioned -L １ - The heterocyclyl in the heterocyclyl has one or more R groups １１ It may also be replaced by each L １ However, bonding, -C(R Ｌ１ ) (Caution Ｌ１ )-, -O-, -S-, -SO-, -SO ２ -, -CO-, and -N(R Ｌ１ ) - Selected independently from each R Ｌ１ However, independently, hydrogen or C １～５ It is an alkyl group, and furthermore, it has two R groups bonded to the same carbon atom. Ｌ１ The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, which may also bond to each other and together with the carbon atoms to which they are bonded to form a cycloalkyl or heterocycloalkyl.

8. R １ However, one or more bases R １１ The compound according to claim 1, wherein the phenyl is substituted with a phenyl compound, or a pharmaceutically acceptable salt or solvate thereof.

9. R １ However, 3-R １１ -4-R １１ -Phenyl or 3-R １１ -4-R １１ -5-R １１ - Phenyl, and each R １１ However, halogen, C １～５ Haloalkyl and C １～５ A compound according to claim 1, independently selected from alkyl groups, or a pharmaceutically acceptable salt or solvate thereof.

10. R ２Ａ and R ２Ｂ However, they bond to each other and together with the carbon atoms to which they are bonded, form a cycloalkyl or heterocycloalkyl group, and the cycloalkyl or heterocycloalkyl group has one or more R groups. ２１ The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, which may be substituted with.

11. R ２Ａ and R ２Ｂ However, they bond to each other and together with the carbon atoms to which they are bonded, form cyclopentyl or tetrahydrofuranyl, and the cyclopentyl or tetrahydrofuranyl has one or more R groups. ２１ The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, which may be substituted with.

12. R ２Ａ and R ２Ｂ However, each is independent of C １～５ A compound according to claim 1, wherein it is alkyl, or a pharmaceutically acceptable salt or solvate thereof.

13. The compound according to claim 1, wherein L is -CO-, or a pharmaceutically acceptable salt or solvate thereof.

14. Group A is a heterocycloalkyl group bonded to group L via a cyclic nitrogen atom, and the heterocycloalkyl group is bonded to one or more groups R Ａ The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, which may be substituted with.

15. Group A is 2,2-dimethylpiperazine-1-yl, and the piperazinyl group in the 2,2-dimethylpiperazine-1-yl is one or more groups R Ａ The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, which may be substituted with.

16. 1'-(4-chloro-3-fluorophenyl)-5'-(2,2-dimethyl-3-oxopiperazine-1-carbonyl)-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-2'(1'H)-one; 1'-(4-chloro-3-fluorophenyl)-5'-(2,2-dimethyl-3-oxopiperazine-1-carbonyl)spiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-2'(1'H)-one; 4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-2-one; 8-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione; Methyl 1-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperidine-4-carboxylate; 1-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperidine-4-carboxylic acid; Methyl 6-(4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 4-(1'-(3-chlorophenyl)-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-2-one; 4-(1'-(2-chlorophenyl)-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-2-one; 4-(3,3-dimethyl-1-(thiophen-3-yl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-2-one; 4-(1-(3,4-difluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-2-one; Methyl 6-(4-(1-(3,4-difluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(3,4-difluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 4-(1-(4-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-2-one; Methyl 6-(4-(1-(3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-2-one; 4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-1-ethyl-3,3-dimethylpiperazine-2-one; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-yl)(3,3-dimethylmorpholino)methanone; tert-butyl4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-carboxylate; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-yl)(2,2-dimethylpiperazine-1-yl)methanone; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-yl)(4-ethyl-2,2-dimethylpiperazine-1-yl)methanone; 1-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)ethane-1-one; Ethyl 4-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-oxobutanoate; 4-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-oxobutanoic acid; Ethyl 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-5-oxopentanoate; 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-5-oxopentanoic acid; 8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-1-methyl-1,3,8-triazaspiro[4.5]decane-4-one; 2-(3-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-azabicyclo[3.1.0]hexane-6-yl)acetic acid; Methyl 2-(3-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-azabicyclo[3.1.0]hexane-6-yl) acetate; Methyl 2-((1R,5S,6S)-3-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-azabicyclo[3.1.0]hexane-6-yl) acetate; 2-((1R,5S,6S)-3-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-azabicyclo[3.1.0]hexane-6-yl)acetic acid; Ethyl 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-carboxylate; 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-carboxylic acid; Methyl 2-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-yl) acetate; 2-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-yl)acetic acid; 2-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl)acetic acid; Methyl 2-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl) acetate; Methyl 2-((3R,4S)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl) acetate; 2-((3R,4S)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl)acetic acid; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-methylpyrimidine-5-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-methylpyrimidine-5-carboxylic acid; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyrimidine-5-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-pyrimidine-5-carboxylic acid; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)thiazole-4-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)thiazole-4-carboxylic acid; Methyl 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)butanoic acid; Methyl 3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)butanoate; Methyl(R)-3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)butanoate; (R)-3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)butanoic acid; N-(1-carbamoylcyclopropyl)-1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide; Methyl 6-((2-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)ethyl)(methyl)amino)-2,4-dimethylnicotinate; 6-((2-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide)ethyl)(methyl)amino)-2,4-dimethylnicotinic acid; 1-(4-chloro-3-fluorophenyl)-N-(1-hydroxy-2-methylpropan-2-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide; 1-(4-chloro-3-fluorophenyl)-N-(2-hydroxy-2-methylpropyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide; 4-(1-(4-chloro-3-fluorophenyl)-3-ethyl-3-methyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-2-one; N-(1-carbamoylcyclopropyl)-1-(4-chloro-3-fluorophenyl)-3-ethyl-3-methyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide; 4-(1'-(4-chloro-3-fluorophenyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-2-one; 6-(4-(1'-(4-chloro-3-fluorophenyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopropane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-2-one; 4-(1'-(4-chloro-3-fluorophenyl)-1',2',4,5-tetrahydro-2H-spiro[furan-3,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-2-one; Methyl 6-(4-(1'-(4-chloro-3-fluorophenyl)-1',2',4,5-tetrahydro-2H-spiro[furan-3,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1'-(4-chloro-3-fluorophenyl)-1',2',4,5-tetrahydro-2H-spiro[furan-3,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 4-(8-(4-chloro-3-fluorophenyl)-3a-methyl-3,3a,8,8a-tetrahydro-2H-flu[3',2':4,5]pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-2-one; cis-4-(8-(4-chloro-3-fluorophenyl)-3a-methyl-3,3a,8,8a-tetrahydro-2H-flu[3',2':4,5]pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-2-one; 4-((3aR,8aR)-8-(4-chloro-3-fluorophenyl)-3a-methyl-3,3a,8,8a-tetrahydro-2H-flu[3',2':4,5]pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-2-one; 4-((3aS,8aS)-8-(4-chloro-3-fluorophenyl)-3a-methyl-3,3a,8,8a-tetrahydro-2H-flu[3',2':4,5]pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-2-one; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Ethyl 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-1,3,4-thiadiazole-2-carboxylate; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-yl)(2,2-dimethyl-4-(1,3,4-thiadiazole-2-yl)piperazine-1-yl)methanone; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-methylthiazole-5-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-methylthiazole-5-carboxylic acid; Ethyl 2-(2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-methylthiazole-5-yl) acetate; 2-(2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-methylthiazole-5-yl)acetic acid; Methyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-5-methylthiazole-4-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-5-methylthiazole-4-carboxylic acid; 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-7,7-dimethyl-1,4-diazepan-5-one; 8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-2,8-diazaspiro[4.5]decane-1-one; 8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-2,8-diazaspiro[4.5]decane-3-one; 1-(1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-yl)imidazolidin-2-one; Ethyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-(trifluoromethyl)thiazole-5-carboxylate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-4-(trifluoromethyl)thiazole-5-carboxylic acid; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-N,N-dimethylthiazole-4-carboxamide; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-yl)(4-(4-(4-hydroxypiperidine-1-carbonyl)thiazole-2-yl)-2,2-dimethylpiperazine-1-yl)methanone; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-yl)(2,2-dimethyl-4-(4-(morpholine-4-carbonyl)thiazole-2-yl)piperazine-1-yl)methanone; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)thiazole-4-carboxamide; Methyl 6-(4-(1-(3-fluoro-4-methylphenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(3-fluoro-4-methylphenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-8-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-8-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine-8-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 6-(4-(1'-(4-chloro-3-fluorophenyl)-3,3-difluoro-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 6-(4-(1'-(4-chloro-3-fluorophenyl)-3-fluoro-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-2-en-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-((3S,4S)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl) acetate; 2-((3S,4S)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl)acetic acid; Methyl 2-((3R,4R)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl) acetate; 2-((3R,4R)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl)acetic acid; Ethyl (2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)thiazole-4-carbonyl)glycinate; (2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)thiazole-4-carbonyl)glycine; Methyl 2-((3S,4R)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl) acetate; 2-((3S,4R)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3-methoxypiperidine-4-yl)acetic acid; Methyl 6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-yl)(2,2-dimethyl-4-(4-(4-methylpiperazine-1-carbonyl)thiazole-2-yl)piperazine-1-yl)methanone; Methyl 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-diethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-diethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl) isonicotinate; 2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl) isonicotinic acid; Ethyl 3-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl) isonicotinate; 3-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl) isonicotinic acid; Ethyl 6-((1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-3-yl)amino)nicotinate; 6-((1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-3-yl)amino)nicotinic acid; Ethyl 6-((1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-3-yl)(methyl)amino)nicotinate; 6-((1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-3-yl)(methyl)amino)nicotinate; Methyl 6-(4-(1'-(3,4-difluorophenyl)-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1'-(3,4-difluorophenyl)-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-4-yl) acetate; 2-(2-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-4-yl)acetic acid; Ethyl 2-(5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-2-yl)acetate; 2-(5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-2-yl)acetic acid; Methyl 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; 1'-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)spiro[indoline-3,3'-pyrrolidine]-2-one; 8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one; Ethyl 6-(6-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)nicotinate; 6-(6-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)nicotinic acid; Methyl 2-(1-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)piperidine-4-yl) acetate; 2-(1-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)piperidine-4-yl)acetic acid; 4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-2-one; Methyl 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-3,3-difluoro-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-3,3-difluoro-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Ethyl 2-((1R,5S)-8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-8-azabicyclo[3.2.1]octan-3-yl) acetate; 2-((1R,5S)-8-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-8-azabicyclo[3.2.1]octan-3-yl)acetic acid; Methyl 6-(4-(6-(5-(4-(5-(methoxycarbonyl)-4,6-dimethylpyridine-2-yl)-2,2-dimethylpiperazine-1-carbonyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-1-yl)nicotinoyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-(1-(5-chloropyridine-2-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(6-(5-(4-(5-carboxy-4,6-dimethylpyridine-2-yl)-2,2-dimethylpiperazine-1-carbonyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-1-yl)nicotinoyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 6-(4-(1-(5-chloropyridine-2-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(3,3-dimethyl-1-(pyridine-2-yl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; Ethyl 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-4-(pyridine-2-yl)piperidine-3-carboxylate; (cis)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-4-(pyridine-2-yl)piperidine-3-carboxylic acid; (trans)-1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-4-(pyridine-2-yl)piperidine-3-carboxylic acid; Methyl 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-3-methylpicolinate; 6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-3-methylpicolinic acid; Methyl 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2-methoxynicotinate; 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2-methoxynicotinic acid; Methyl 6-(4-((1S,3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-((1R,3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-((3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-((1S,3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 6-(4-((1R,3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 6-(4-((3R)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-((1S,3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-((1R,3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; Methyl 6-(4-((3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-((1S,3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 6-(4-((1R,3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; 6-(4-((3S)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclopentan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-diethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-diethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)nicotinate; Methyl 5-(4-(1-(3-fluoro-4-(4-(5-(methoxycarbonyl)pyridine-3-yl)-2,2-dimethylpiperazine-1-carbonyl)phenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)nicotinate; 5-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)nicotinic acid; 5-(4-(4-(5-(4-(5-carboxypyridine-3-yl)-2,2-dimethylpiperazine-1-carbonyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-1-yl)-2-fluorobenzoyl)-3,3-dimethylpiperazine-1-yl)nicotinic acid; Methyl 2-(6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-(1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1'-(4-chloro-3-fluorophenyl)-3-methyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)propanoate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)propanoic acid; Methyl 6-(4-(1-(4-cyanocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(4-carbamoylcyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(1-(4,4-difluorocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1-(4,4-difluorocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; 4-(5-(4-(4,6-dimethylpyridine-2-yl)-2,2-dimethylpiperazine-1-carbonyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-1-yl)cyclohexane-1-carbonil; Methyl 2-(6-(4-(1-cyclopentyl-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1-cyclopentyl-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(1-(4-cyanocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1-(4-cyanocyclohexyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5-(3,4-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(3,4-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)-2-methylpropanoate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)-2-methylpropanoic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-8,8-dimethyl-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-8,8-dimethyl-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(4-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(4-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-(5-(3,4-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3,4-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-cyclopentyl-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-cyclopentyl-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3-fluoro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3-fluoro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(4-chloro-3,5-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(4-chloro-3,5-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3-chloro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3-chloro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3-chloro-4-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3-chloro-4-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3-chloro-4-(trifluoromethyl)phenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3-chloro-4-(trifluoromethyl)phenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(3-(4-chloro-3-fluorobenzyl)-1-isobutyl-3-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-6-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(3-(4-chloro-3-fluorobenzyl)-1-isobutyl-3-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-6-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1'-(4-chloro-3-fluorophenyl)-3-methoxy-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(3-fluoro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(3-fluoro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5-(3-chloro-4-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(3-chloro-4-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclopentan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclopentan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(1,3-dihydroisobenzofuran-5-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(4-fluorophenethyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(4-fluorophenethyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-(5-(4-fluorophenethyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 2-(6-(4-(5-(4-fluorophenethyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-(1'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(7,7-dimethyl-5-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(7,7-dimethyl-5-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5-(3-chloro-4-(trifluoromethyl)phenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(3-chloro-4-(trifluoromethyl)phenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5-(3,4-dichlorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(3,4-dichlorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-(5'-(3,4-difluorophenyl)-5',6'-dihydrospiro[cyclopentan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5'-(3,4-difluorophenyl)-5',6'-dihydrospiro[cyclopentan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5'-(3,4-difluorophenyl)-5',6'-dihydrospiro[cyclopentan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5'-(3,4-difluorophenyl)-5',6'-dihydrospiro[cyclopentan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-(5'-(3,4-difluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5'-(3,4-difluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(3,3-dimethyl-5'-(3,4,5-trifluorophenyl)-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(3,3-dimethyl-5'-(3,4,5-trifluorophenyl)-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(((1s,3s)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(((1r,3r)-1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1'-(4-chloro-3-fluorophenyl)-3-(methoxymethyl)-1',2'-dihydrospiro[cyclobutan-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5-(4-chloro-3,5-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3,5-difluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclopentan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5'-(4-chloro-3-fluorophenyl)-5',6'-dihydrospiro[cyclopentan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5'-(3,4-difluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5'-(3,4-difluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-(5'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(5-(3,4-dichlorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(5-(3,4-dichlorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(3-chloro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate 2-(6-(4-(5-(3-chloro-4-methylphenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-8-methoxy-7,7-dimethyl-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-8-methoxy-7,7-dimethyl-5,6,7,8-tetrahydro-1,5-naphthyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-6-methoxy-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-6-methoxy-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(3-(4-chloro-3-fluorophenyl)-1-isobutyl-3-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-6-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(3-(4-chloro-3-fluorophenyl)-1-isobutyl-3-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-6-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-6-hydroxy-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 8-(4-(5'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-8-oxoctanoate; 8-(4-(5'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-8-oxooctanoic acid; N-(37-(4-(5'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-1-yl)-3-methyl-4,17,30,37-tetraoxo-7,10,13,20,23,26-hexaoxa-3,16,29-triazaheptatriacontyl)-N-methylpalmitamide; Methyl 4-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,6-dimethylnicotinate; 4-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,6-dimethylnicotinic acid; Methyl 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-6-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; 1-(1-((5'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-yl)sulfonyl)piperidine-4-yl)imidazolidined-2-one; Methyl 2-(6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrazino[2,3-b][1,4]oxazine-7-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(4-(4-chloro-3-fluorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrazino[2,3-b][1,4]oxazine-7-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; tert-butyl 2-(4-(5-(2-methoxy-2-oxoethyl)pyridine-2-yl)-2,2-dimethylpiperazine-1-carbonyl)-7,7-dimethyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; Methyl 6-(4-(1-(3-fluoro-4-(trifluoromethyl)phenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(3-fluoro-4-(trifluoromethyl)phenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(7,7-dimethyl-5-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(7,7-dimethyl-5-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 6-(4-(1-(4-cyclopropylphenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinate; 6-(4-(1-(4-cyclopropylphenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazine-1-yl)-2,4-dimethylnicotinic acid; Methyl 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-3,7,7-trimethyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetate; 2-(6-(4-(5-(4-chloro-3-fluorophenyl)-3,7,7-trimethyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-2-carbonyl)-3,3-dimethylpiperazine-1-yl)pyridine-3-yl)acetic acid; 4-(5'-(3,4-difluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutan-1,7'-pyrrolo[2,3-b]pyrazine]-2'-carbonyl)-3,3-dimethylpiperazine-2-one; Alternatively, the compound according to claim 1, selected from any pharmaceutically acceptable salt or solvate of any of the aforementioned compounds.

17. A compound according to any one of claims 1 to 16 or a pharmaceutically acceptable salt or solvate thereof, conjugated to a membrane anchor via a linker.

18. A pharmaceutical composition comprising a compound according to any one of claims 1 to 16 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

19. The pharmaceutical composition according to claim 18 for use in the treatment or prevention of pain, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, central nervous system disorders, spinal cord injuries, metabolic disorders, gastrointestinal disorders, cardiovascular disorders, fibrous disorders, respiratory disorders, skin disorders, allergic disorders, or cancer.

20. Neuropathic pain, inflammatory pain, cancer pain, postoperative incision pain, fracture pain, osteoporotic fracture pain, gouty joint pain, chronic pain, spinal cord injury, atopic dermatitis, contact dermatitis, dry skin dermatitis, seborrheic dermatitis, arthritis, rheumatoid arthritis, osteoarthritis, psoriasis, psoriatic arthritis, multiple sclerosis, non-alcoholic fatty liver disease, obesity, diabetes, adipose tissue inflammation, pancreatitis, metabolic syndrome, PAR-2 ​​related metabolic dysfunction, periodontitis, gingivitis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, peptic ulcer disease, infectious enteritis, irritable bowel syndrome, atherosclerosis, asthma, interstitial The pharmaceutical composition according to claim 18 for use in the treatment or prevention of pulmonary diseases, pulmonary fibrosis, rheumatoid arthritis-associated interstitial lung disease, hepatic fibrosis, cystic fibrosis, renal fibrosis, peritoneal fibrosis, pancreatic fibrosis, intestinal fibrosis, cardiac fibrosis, dermatofibrosis, systemic lupus erythematosus, scleroderma, eczema, acne, rosacea, post-inflammatory hyperpigmentation, lichen planus, pruritus, polymyositis, vasculitis, Wegener's granulomatosis, Netherton syndrome, dermatomyositis, uveitis, cirrhosis, Alzheimer's disease, Parkinson's disease, dust mite allergy, cockroach allergy, or allergic asthma.

21. The pharmaceutical composition according to claim 18 for use in the treatment or prevention of cancer.

22. The pharmaceutical composition according to claim 21, wherein the cancer is selected from colorectal cancer, colon cancer, stomach cancer, rectal cancer, liver cancer, breast cancer, pancreatic cancer, cervical cancer, prostate cancer, ovarian cancer, endometrial cancer, uterine sarcoma, germ cell cancer, esophageal cancer, leukemia, lung cancer, adrenal cancer, bile duct cancer, bladder cancer, head and neck cancer, kidney cancer, lymphoma, mesothelioma, sarcoma, melanoma, thyroid cancer, thymic cancer, and glioblastoma.

23. The pharmaceutical composition according to claim 21, for use in combination administration with one or more immune checkpoint inhibitors.

24. A pharmaceutical composition comprising an immune checkpoint inhibitor for use in the treatment or prevention of cancer, wherein the composition is for combination administration with a compound according to any one of claims 1 to 16 or a pharmaceutically acceptable salt or solvate thereof.

25. The pharmaceutical composition according to claim 23, wherein the immune checkpoint inhibitor is selected from anti-CTLA-4 antibody, anti-PD-1 antibody, anti-PD-L1 antibody, anti-TIGIT antibody, and anti-LAG3 antibody.

26. The aforementioned immune checkpoint inhibitors are ipilimumab, tremelimumab, nivolumab, pembrolizumab, pidilizumab, semiprimab, dostallimab, spartalizumab, camrelizumab, cintilimab, tislerizumab, tripalimab, zimbererimab, AMP-224, AMP-514, JTX-4014, INCMGA00012, APE02058, atezolizumab, avelumab, durvalumab, KN035, CK-301, BMS-936559, MEDI4736, The pharmaceutical composition according to claim 25, selected from MPDL3280A, MDX-1105, MEDI6469, vintrafusp alfa, tiragolumab, vivostrimab, dombanarimab, etigirimab, BMS-986207, EOS-448, COM902, ASP8374, SEA-TGT, BGB-A1217, IBI-939, M6223, leratrimab, yeramirimab, enserimab, teboterimab, REGN3767, FS118, IMP701, and IMP731.

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