Novel PAR-2 inhibitors

Abstract

The present invention provides novel compounds of formula (I) and pharmaceutical compositions containing these compounds. The compounds of the formula (I) can be used as PAR-2 inhibitors to play a role, so that the compounds have great advantages in the aspect of treatment; in particular in the treatment or prevention of pain, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, central nervous system disorders, spinal cord injury, metabolic disorders, gastrointestinal disorders, cardiovascular disorders, fibrosis disorders, respiratory disorders, skin disorders, allergic disorders or cancer. # imgabs0 #

Description

[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, which makes these compounds very advantageous for use in treatment, 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.

[0002] Protease-activated receptor (PAR) family

[0003] G protein-coupled receptors (GPCRs) form the largest family of human membrane proteins (~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).

[0004] 2% of the human genome encodes proteases (also known as proteolytic enzymes), which indicates their importance in the normal functioning of the human body (Hollenberg et al., Br. J. Pharmacol., 2014, 171(5):1180-94). In fact, it has been shown that certain soluble and membrane-bound proteases can regulate cell function by cleaving GPCRs on the cell surface to activate or inactivate 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 (Marcfarlane 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, myocytes, astrocytes, neurons, epithelial cells and fibroblasts, and are involved in a large number of physiological and pathophysiological functions (Ossovskaya et al., Physiol. Rev., 2004, 84(2):579-621).

[0005] PAR-2: Mechanism of Action

[0006] Activation of PAR involves the cleavage of the extracellular N-terminal portion of the receptor by proteases at specific sites. This unmasks the amino-terminal amino acid sequence, which folds back to act as a "tethered ligand" (TL): it binds to a conserved region of the second extracellular loop of the cleaved receptor and triggers intracellular signaling (Ossovskaya et al., Physiol. Rev., 2004, 84(2):579-621; Hollenberg et al., Br. J. Pharmacol., 2014, 171(5):1180-94).

[0007] PAR-2 ​​is activated by several host- and pathogen-derived serine proteases, such as trypsin, mast cell tryptase, kallikrein, and members of the coagulation cascade TF-FVIIa and FVa-FXa. 34 ↓S 35 The receptor is cleaved at LIGKV and exposes the bound ligand SLIGKV. An artificial in vitro synthesized peptide corresponding to TL(SLIGKV) can activate the receptor without cleavage.

[0008] PAR-2 ​​activation induces multiple G proteins, such as G q , G i and G 12 / 13 The best-described pathway to date involves its interaction with G q PAR2 is a key regulator of cellular metabolism and is involved in the mobilization of intracellular calcium, which influences the function of multiple cell types. Following repeated activation, PAR2 is rapidly desensitized by endocytosis and its targeting to lysosomes via a β-arrestin-dependent mechanism (Ossovskaya et al., Physiol. Rev., 2004, 84(2):579-621).

[0009] PAR-2 ​​under physiological conditions

[0010] PAR-2 ​​has been shown to have key functions in a variety of organs (Ossovskaya et al., Physiol. Rev., 2004, 84(2):579-621). PAR-2 ​​is expressed in neurons and glial cells in the brain. PAR-2 ​​has also been found in peripheral spinal cord afferent neurons and nociceptive DRG neurons. PAR-2 ​​signaling is involved in the survival, sensitization, and signaling of these cells, thereby controlling neuronal damage, inflammation, and pain.

[0011] PAR-2 ​​is involved in cardiovascular system function. Its activation can induce relaxation or constriction in certain blood vessels, such as the pulmonary, coronary, and intramyocardial arteries, thereby regulating blood flow. It also controls inflammation and endothelial repair, which affects vascular permeability.

[0012] PAR-2 ​​expression has been detected in the small intestine, colon, liver, pancreas, and stomach of the gastrointestinal system. PAR-2 ​​activation is involved in regulating intestinal mucosal ion transport, gastric longitudinal muscle contraction, pancreatic, salivary, and gastric juice secretion, myenteric neuronal excitation, intestinal barrier integrity, and intestinal epithelial prostaglandin release. Therefore, PAR-2 ​​plays a key role in controlling humoral secretion, intestinal inflammation, and gastrointestinal hyperalgesia.

[0013] PAR-2 ​​is involved in airway function because it is expressed in epithelial and endothelial cells in the lungs. Its activation has been shown to regulate bronchodilation or bronchoconstriction (depending on the experimental system used), ion transport in the airway epithelium, proliferation and activation of airway smooth muscle cells and lung fibroblasts. PAR-2 ​​can therefore regulate airway resistance, lung inflammation and pulmonary fibrosis.

[0014] In the skin, PAR-2 ​​expression has been detected in keratinocytes, microvessels, and immune cells. Its activation is involved in skin pigmentation, skin inflammation, and wound healing.

[0015] Finally, PAR-2 ​​expression has been detected in immune cells such as macrophages, where it affects cell maturation and cytokine secretion, thereby regulating inflammation.

[0016] PAR-2 ​​in pathological conditions

[0017] Because PAR-2 ​​regulates numerous and diverse biological processes, it is not surprising that dysregulation of PAR-2 ​​is associated with numerous pathological conditions.

[0018] PAR-2 ​​is expressed in the brain, dorsal root ganglia, spinal afferent neurons, and nociceptive DRG neurons. It is activated by proteases, such as tryptase released by mast cells, leading to calcium and cAMP signaling (Steinhoff et al., Nat Med, 2000, 6(2):151-8; Zhao et al., J Biol Chem., 2015, 290(22):13875-87). This promotes inflammation and hyperalgesia through the release of CGRP (calcitonin gene-related peptide) and SP (substance P) in spinal afferent neurons and sensitization of transient receptor potential vanilloids (TRPVs) TRPV1 and TRPV4 in sensory neurons (Vergnolle et al., Nat Med, 2001, 6(2):151-8; Steinhoff et al., Nat Med, 2000, 6(2):151-8; Amadesi et al., J Neurosci, 2004, 24(18):4300-12; Grant et al., J Physiol, 2007, 578(Pt 3), 715-33; Jimenez Vargas et al., Proc Natl Acad Sci USA, 2018, 115(31):E7438-E7447). This is supported by a wealth 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, 440-51). PAR-2 ​​is therefore clearly involved in the generation and transmission of pain signals, neurogenic inflammation, and nociception.

[0019] The expression of PAR-2 ​​and proteases in the spinal cord increases after contusion-compression injury (Radulovic et al., Neurobiol Dis, 2015, 83, 75-89; Li et al., Physiol. Res., 2019, 68(2): 305-316). Their activation can lead to cAMP signaling in oligodendrocytes (Yoon et al., Glia, 2017, 65(12): 2070-2086). In vitro and in vivo experiments in rodents have demonstrated that inhibition of PAR-2 ​​signaling during experimental spinal cord injury reduces inflammation, scar formation, and mechanical and thermal hyperalgesia, and improves oligodendrocyte remyelination and motor 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.

[0020] Immune system disorders are the basis of many diseases. In all cases, the immune system attacks normal components of the body that it perceives as foreign. The immune system is pathogenic and leads to specific organ lesions (such as type 1 diabetes in the pancreas or multiple sclerosis in the brain) or systemic lesions (such as rheumatoid arthritis or systemic lupus erythematosus, SLE).

[0021] Cytokines are small proteins involved in cell signaling that coordinate the immune response. Their imbalance underlies the pathogenesis of autoinflammatory diseases. These conditions are characterized by abnormal immune activation, infiltration, and cytokine production. They include, for example, rheumatoid inflammatory diseases, inflammatory diseases of the skin, inflammatory diseases of the lungs, inflammatory diseases of the muscles, inflammatory diseases of the intestines, inflammatory diseases of the brain, and autoimmune diseases.

[0022] Although autoinflammatory diseases are chronic, some conditions lead to acute immune disorders. In fact, sudden excessive and uncontrolled release of proinflammatory cytokines, also known as cytokine storm, 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, F1000 Res, 2016, 5, 2909; Tisoncik JR et al., Microbiol Mol Biol Rev, 2012, 76 (1): 16-32). In these cases, dysregulated immune responses and subsequent excessive inflammation may lead to fatal multiple organ failure.

[0023] Because PAR-2 ​​affects the production of inflammatory cytokines and the function of various organs, many studies have demonstrated that it is a promising therapeutic target for various autoinflammatory diseases.

[0024] The expression of proteases 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 nonalcoholic steatohepatitis (Rana et al., Mol Metab, 2019, 29:99-113), and actively demyelinated areas in the brains of patients with multiple sclerosis (Noorbakhsh et al., J Exp Med, 2006, 203(2):425-35).

[0025] Here, PAR-2 ​​activation leads to calcium signaling in several cells, such as osteoblasts, fibroblasts, monocytes, 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 signal transduction is associated with cell maturation and / or migration, activation, and secretion of inflammatory cytokines such as IL-8, IL6, 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 by acting on the survival of key cells (e.g., neurons and chondrocytes, respectively) 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).Notably, other signaling pathways, such as cyclic AMP in alveolar macrophages and Gi in hepatocytes appear 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).

[0026] It has been clearly demonstrated that in vivo, in mouse models, inhibition of PAR-2 ​​signaling, either pharmacologically or by genetic modification, significantly alleviates the symptoms of atherosclerosis, idiopathic pulmonary fibrosis, atopic dermatitis, multiple sclerosis, arthritis, nonalcoholic 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 key role in the molecular and cellular mechanisms of the pathogenesis of autoinflammatory diseases.

[0027] PAR-2-dependent inflammation also impairs cellular metabolism and promotes insulin resistance, which in turn contributes to the pathogenesis of diabetes, obesity, and metabolic syndrome. In fact, PAR-2 ​​expression in adipocyte tissue is associated with increased BMI in volunteers, and inhibition of PAR-2 ​​signaling alleviates 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).

[0028] Many airborne allergens from house dust mites and cockroach allergens contain protease activity. This protease activity activates PAR-2 ​​expressed on human airway epithelial cells, endothelial cells, and immune cells and induces calcium signaling. This ultimately leads to the release of inflammatory cytokines and angiogenic responses based on the pathogenesis 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, during allergen stimulation, functional blockade of PAR-2 ​​in the airways improved allergen-induced inflammation and airway hyperresponsiveness in mice (Asaduzzaman et al., Clin Exp Allergy, 2015, 45 (12): 1844-55).

[0029] The expression of PAR-2 ​​and proteases is also significantly increased in many cancer types, such as cervical squamous cell carcinoma, endocervical adenocarcinoma, colon adenocarcinoma, esophageal cancer, glioblastoma multiforme, acute myeloid leukemia, lung adenocarcinoma, lung squamous cell carcinoma, ovarian serous cystadenocarcinoma, pancreatic cancer, prostate cancer, rectal adenocarcinoma, gastric adenocarcinoma, testicular germ cell tumor, uterine corpus endometrial cancer, uterine carcinosarcoma, 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 leads to several 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 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). Expression of PAR-2 ​​on other cells of the tumor microenvironment, such as immune cells, fibroblasts, endothelial cells, and DRG neurons, can also control the immune response to cancer cells, fibrosis, 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 at al., Oncol Lett, 2018, 16(2):1513-20; Tu et al., J Neurosci, 2021, 41(1):193-210).In vivo, inhibition of PAR-2 ​​has been shown to be an effective way to reduce tumor growth and increase survival in mouse models of different cancers such as breast cancer, liver cancer, and colon cancer (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 several syngeneic mouse models, inhibition of PAR2 or one of its ligands leads to reduced infiltration of immunosuppressive tumor-associated macrophages and regulatory T cells, while increasing cytotoxic T cells in tumors and increasing antigen-presenting cells in draining lymph nodes; this releases (unleashed) anti-tumor immune responses and increases the efficacy of currently clinically used immune checkpoint inhibitors (Graf et al., Sci Immunol, 2019, 4(39):eaaw8405). Therefore, PAR-2 ​​constitutes a promising therapeutic target in oncology and immuno-oncology.

[0030] Given the role of PAR-2 ​​in several pathophysiological conditions, inhibitors of this receptor could have therapeutic applications in a wide variety of human diseases, which has sparked considerable interest in the development of such compounds within the pharmaceutical industry. Various PAR-2 ​​inhibitors and their therapeutic use have been proposed, for example in the following documents: Yau et al., Expert Opin Ther Pat, 2016, 26(4):471-83; Jiang et al., J Pharmacol Exp Ther, 2018, 364(2):246-57; WO 2004 / 002418; WO 2005 / 030773; WO 2012 / 012843; WO 2012 / 026765; WO 2012 / 026766; WO 2012 / 101453; WO 2015 / 048245; WO 2016 / 154075; WO 2017 / 194716; WO 2017 / 197463; WO 2018 / 043461 (EP 3 508 487); WO 2018 / 057588;WO 2019 / 163956 (EP 3 760 631); WO 2019 / 199800;JP 2020 / 007262;And WO 2021 / 106864. However, despite efforts in the past 10 years, no PAR-2 ​​inhibitors have yet entered the market (Yau et al., Expert Opin Ther Pat., 2016, 26(4):471-83). Therefore, there is still an unmet need for new and / or improved PAR-2 ​​inhibitors with high efficacy, selectivity and bioavailability.

[0031] The present invention satisfies such needs and solves the problem of providing novel and highly effective PAR-2 ​​inhibitors. In particular, it has been surprisingly found that the compounds of formula (I) provided herein are potent inhibitors of PAR-2 ​​signaling, which makes these compounds very advantageous for use in treatment, including in particular in the treatment or prevention of pain, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, central nervous system disorders, spinal cord injury, metabolic disorders, gastrointestinal disorders, cardiovascular disorders, fibrotic disorders, respiratory disorders, skin disorders, allergic disorders or cancer.

[0032] Therefore, the present invention provides a compound of the following formula (I)

[0033]

[0034] or a pharmaceutically acceptable salt or solvate thereof.

[0035] In formula (I), ring B is a non-aromatic C 4-8A carbocyclic or non-aromatic 4- to 8-membered heterocyclic ring, wherein the ring B is fused to the ring D, wherein the carbocyclic or heterocyclic ring: (i) is fused to the ring D; 1 (ii) a group R connected to the same ring carbon atom of the carbocyclic ring or the heterocyclic ring 2A and R 2B and (iii) optionally substituted by one or more groups R Y replace.

[0036] Ring D is a 5- or 6-membered heteroaromatic ring, said ring D being fused to ring B, wherein said heteroaromatic ring comprises at least one nitrogen ring atom, wherein said heteroaromatic ring is substituted with a group -LA, and wherein said heteroaromatic ring is optionally substituted with one or more groups R X replace.

[0037] R 1 Selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -(C 0-5 Alkylene)-carbocyclyl, and -(C 0-5 Alkylene) -heterocyclic group, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, and said-(C 0-5 The alkylene groups in the heterocyclic group are each optionally substituted by one or more groups R 12 Substituted, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, or said-(C 0-5 One or more -CH2- units contained in the alkylene group in the alkylene)-heterocyclyl group are each optionally independently selected from -C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, wherein each R L1 are independently hydrogen or C 1-5 Alkyl groups, in which two groups R are attached to the same carbon atom L1 They may also be linked to each other to form, together with the carbon atoms to which they are linked, a cycloalkyl group or a heterocycloalkyl group, and wherein said -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R 11 replace.

[0038] Each R 11 Independently selected from C 1-5 Alkyl, C 2-5Alkenyl, 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 0-3Alkylene)-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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace.

[0039] Each R 12Independently selected from -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), carbocyclyl, heterocyclyl, and -L Z -RZ wherein the carbocyclyl and the heterocyclyl are each optionally substituted by one or more groups R Cyc replace.

[0040] R 2A and R 2B are linked to each other to form, together with the carbon atoms to which they are attached, a cycloalkyl, a cycloalkenyl, a heterocycloalkyl, or a heterocycloalkenyl, wherein the cycloalkyl, the cycloalkenyl, the heterocycloalkyl or the heterocycloalkenyl is optionally substituted by one or more groups R 21 replace;

[0041] or R 2A and R 2B Each independently selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -(C 0-5 Alkylene)-carbocyclyl, and -(C 0-5 Alkylene) -heterocyclic group, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, and said-(C 0-5 The alkylene groups in the heterocyclic group are each optionally substituted by one or more groups R 22 Substituted, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, or said-(C 0-5 The one or more -CH2- units contained in the alkylene in the alkylene)-heterocyclyl are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, wherein the -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace,

[0042] where R 2A and group R Y They may also be linked to each other to form, together with the ring atoms to which they are attached, a carbocyclic group or a heterocyclic group, wherein the carbocyclic group or the heterocyclic group is optionally substituted by one or more groups R Cyc replace.

[0043] Each R 21 Independently selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -(C 0-3Alkylene)-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 0-3Alkylene)-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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace.

[0044] Each R 22 Independently selected from -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), carbocyclyl, heterocyclyl, and -L Z -R Zwherein the carbocyclyl and the heterocyclyl are each optionally substituted by one or more groups R Cyc replace.

[0045] Each R X Independently selected from 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), -(C0-3 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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace.

[0046] Each R Y Independently selected from 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, -(C0-3 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 group, -(C 0-3alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace;

[0047] Among them, any two groups R attached to the same ring carbon atom Y (i) may also be linked to each other to form, together with the carbon atoms to which they are linked, a cycloalkyl group or a heterocycloalkyl group, wherein the cycloalkyl group or the heterocycloalkyl group is optionally substituted by one or more groups R Cyc or (ii) may mutually form a group =0.

[0048] L is selected from -CO-, -SO- and -SO2-.

[0049] Group A is -N(-R N )-R N or a heterocyclic group, wherein the heterocyclic group is linked to the group L via a ring nitrogen atom, and wherein the heterocyclic group is optionally substituted by one or more groups R A replace.

[0050] Each R N are independently selected from 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-(C1-5 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(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)-carbocyclyl, and -(C 0-8 Alkylene)-heterocyclic group, wherein the C 1-8Alkyl, the C 2-8 Alkenyl, the C 2-8 Alkynyl, and the above C 0-8 Alkylene and C 1-8 One or more -CH2- units contained in any one of the alkylene groups are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, wherein the -(C 0-8 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-8 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc substituted, and wherein at least one group R N Not hydrogen.

[0051] Each R A Independently selected from 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(C1-5 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 1-5Alkyl), -(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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc and further, wherein any two groups R connected to the same carbon atom of group A are A They may also be linked to each other to form, together with the carbon atoms to which they are attached, a cycloalkyl group or a heterocycloalkyl group, wherein the cycloalkyl group or the heterocycloalkyl group is optionally substituted by one or more groups R Cyc replace.

[0052] Each R Cyc Independently selected from 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 Halogenated alkyl), -CN, -CHO, -CO(C 1-5 alkyl), -COOH, -COO(C 1-5alkyl), -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)(-OC 1-5 alkyl), -P(=O)(-OC 1-5 Alkyl)(-OC 1-5 Alkyl), -(C 0-3 Alkylene)-cycloalkyl, -(C 0-3 alkylene)-heterocycloalkyl, and -L Z -R Z .

[0053] Each L Z independently selected from covalent bonds, C 1-7 Alkylene, C 2-7 Alkenylene, and C 2-7 Alkynylene, wherein the alkylene, the alkenylene and the alkynylene are each optionally substituted by one or more 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 1-5Alkyl)(C 1-5 alkyl) group, and further, wherein the one or more -CH2- units contained in the alkylene, the alkenylene or the alkynylene are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2- groups.

[0054] Each R Z Independently selected from -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 Halogenated alkyl), -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 1-5Alkyl)(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, wherein the aryl, the heteroaryl, the cycloalkyl and the heterocycloalkyl are each optionally substituted by one or more 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), -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 1-5alkyl), carbocyclyl, and heterocyclyl, wherein the carbocyclyl and the heterocyclyl are each optionally substituted by one or more independently selected 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), and -SO2-(C 1-5 alkyl) groups.

[0055] Preferably, the following conditions apply to compounds of formula (I):

[0056] – If Ring B is a pyrrolidinyl ring and Ring D is a pyridyl ring, R 2A and R 2B are linked to each other to form a cyclopropyl group together with the carbon atoms to which they are attached, L is -CO-, and group A is morpholin-4-yl, then R1 Not 5-R 11 -pyrimidin-2-yl or acetyl;

[0057] – If 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 Each is methyl, R 1 is optionally replaced by one or more groups R 11 Substituted phenyl, L is -CO-, and group A is -NH-R N , then R N is not a heterocycloalkyl group containing one oxidized sulfur ring atom, wherein all other ring atoms are carbon atoms, and said heterocycloalkyl group is substituted with methyl;

[0058] – If ring B and ring D together form 3-R X -4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring, R X is -OH, R 2A and R 2B One of them is a methyl group, R 2A and R 2B The other one is -CON(-CH3)2, R 1 is methyl, L is -CO-, and group A is -NH-R N , then R N is not 4-fluorobenzyl; and

[0059] – If 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 group A is -NH-R N , and R 1 is -CH2-phenyl or -CH2-pyridyl, wherein the phenyl group in the -CH2-phenyl group and the pyridyl group in the -CH2-pyridyl group are each optionally substituted by one or more groups R 11 Substitution, then R 2A and R 2B Not meth.

[0060] The present invention also relates to a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable excipient. Therefore, the present invention relates to a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or any one of the above entities and a pharmaceutically acceptable excipient, for use as a medicament.

[0061] The present invention also relates to a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any of the above entities and a pharmaceutically acceptable excipient, for use in treating or preventing a PAR-2 ​​mediated disease or disorder. Accordingly, the present invention particularly provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient, for use in treating or preventing a PAR-2 ​​mediated disease or disorder.

[0062] 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 treating or preventing a disease or disorder mediated by PAR-2.

[0063] Likewise, the present invention relates to a method for treating or preventing a PAR-2 ​​mediated disease or disorder, comprising administering to an individual (preferably a human) in need thereof a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any of the aforementioned entities and a pharmaceutically acceptable excipient. It should be understood that according to this method, a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof (or a pharmaceutical composition thereof) is administered.

[0064] As described above, the disease disorders treated or prevented using the compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof (or corresponding pharmaceutical compositions) according to the present invention include any PAR-2 ​​mediated disease or disorder. Preferably, the disease / disorder treated or prevented according to the present invention is pain (e.g., chronic pain), an autoimmune disorder, an autoinflammatory disorder, an inflammatory disorder (e.g., a rheumatic inflammatory disorder, a skin inflammatory disorder, a lung inflammatory disorder, a muscle inflammatory disorder, an intestinal inflammatory disorder, or an inflammatory disorder of the brain), a central nervous system disorder, a spinal cord injury, a metabolic disorder, a gastrointestinal disorder, a cardiovascular disorder, a fibrotic disorder, a respiratory disorder, a skin disorder, an allergic disorder, or a cancer.More preferably, the disease / disorder treated or prevented according to the present invention is selected from the group consisting of neuropathic pain, inflammatory pain, cancer pain, postoperative incisional 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), fatty inflammation, pancreatitis, metabolic syndrome, PAR-2-related metabolites, inflammatory bowel disease ... Metabolic dysfunction, periodontitis, gingivitis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, peptic ulcer disease (e.g., gastric or duodenal ulcer), infectious enteritis, irritable bowel syndrome, atherosclerosis, asthma, interstitial lung disease, pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis), interstitial lung disease associated with rheumatoid arthritis, 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 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 mite allergy), cockroach allergy, allergic asthma, colorectal cancer, colon cancer (e.g., colon adenocarcinoma), stomach 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 cystic fibrosis), In some embodiments, the present invention may include but is not limited to: adenocarcinoma, endometrial cancer (e.g., uterine corpus endometrial cancer), uterine sarcoma (e.g., uterine carcinosarcoma), 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 gland cancer (e.g., adrenocortical carcinoma), bile duct cancer (e.g., biliary tract cancer), bladder cancer (e.g., urothelial bladder carcinoma), head and neck cancer, kidney cancer (e.g., renal chromophobe cell carcinoma, renal cell carcinoma, renal clear cell carcinoma, or renal papillary cell carcinoma), lymphoma (e.g., diffuse large B-cell lymphoma), mesothelioma, sarcoma, melanoma (e.g., cutaneous melanoma or uveal melanoma), thyroid cancer, thymic cancer (e.g., thymoma), or glioblastoma.

[0065] Therefore, the present invention particularly relates to a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any one of the above entities and a pharmaceutically acceptable excipient, for use in treating or preventing neuropathic pain, inflammatory pain, cancer pain, postoperative incisional 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, lipopolysaccharide ... Fat inflammation, pancreatitis, metabolic syndrome, PAR-2 ​​related metabolic dysfunction, periodontitis, gingivitis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, peptic ulcer disease (such as gastric ulcer or duodenal ulcer), infectious enteritis, irritable bowel syndrome, atherosclerosis, asthma, interstitial lung disease, pulmonary fibrosis (such as idiopathic pulmonary fibrosis), interstitial lung disease associated with rheumatoid arthritis, 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 mite allergy), cockroach allergy, allergic asthma, or cancer (e.g., colorectal cancer, colon cancer (e.g., colon adenocarcinoma), stomach 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., In some embodiments, the present invention may include but is not limited to: endometrial cancer, uterine corpus endometrial cancer, uterine sarcoma (e.g., uterine carcinosarcoma), 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 gland cancer (e.g., adrenocortical carcinoma), bile duct cancer (e.g., biliary tract cancer), bladder cancer (e.g., urothelial bladder carcinoma), head and neck cancer, kidney cancer (e.g., chromophobe renal cell carcinoma, renal cell carcinoma, clear cell renal cell carcinoma, or papillary renal cell carcinoma), lymphoma (e.g., diffuse large B-cell lymphoma), mesothelioma, sarcoma, melanoma (e.g., cutaneous melanoma or uveal melanoma), thyroid cancer, thymic cancer (e.g., thymoma), or glioblastoma.

[0066] The present invention also relates to a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is bound to a membrane anchor via a linker. The corresponding conjugate can replace the compound of formula (I) for any of the uses or purposes described herein, such as for treating or preventing PAR-2-mediated diseases or disorders, including any of the diseases / disorders mentioned above. The advantage of such conjugates is that they tether the bound compound of formula (I) to the cell membrane near PAR-2, thereby promoting its interaction with PAR-2.

[0067] The membrane anchor can be any moiety, in particular a hydrophobic moiety or a lipid moiety, that is capable of inserting / partitioning into a lipid membrane (preferably a cell membrane); thereby "anchoring" the bound compound of formula (I) to the corresponding lipid membrane. For example, the membrane anchor can be C 12-20 Alkanoyl (e.g., hexadecanoyl, -CO-(CH2) 14 -CH3), cholesterol, cholestanol, sphingolipids or glycophosphatidylinositol (GPI). The membrane anchor may also be, for example, a moiety of formula (II), (III), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV) or (XV), as described and defined in WO 2017 / 197463, in particular pages 10 to 15 of WO 2017 / 197463, which is incorporated herein by reference. The membrane anchor may also be, for example, a raftophile A or A', or formula 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 a portion of any one of 1900b, as described and defined in WO 2005 / 097199, which is incorporated herein by reference.

[0068] The joint is covalently bound to the compound (or its pharmaceutically acceptable salt or solvate) of film anchor and formula (I). Although the joint is not particularly limited, its length is preferably about 1nm to about 50nm, and / or preferably provides a distance of at least 8 atoms between the compound of formula (I) and film anchor. For example, the joint can include one or more polyethylene glycol (PEG) units (or be composed of one or more polyethylene glycol (PEG) units), or can include a peptide (the peptide can be composed of, for example, 2 to 200 amino acid residues) (or be composed of a peptide (the peptide can be composed of, for example, 2 to 200 amino acid residues)). The joint can also be a part of, for example, formula (IV), (XX), (XXI) or (XXII), as described and defined in WO 2017 / 197463, particularly pages 15 to 18 of WO 2017 / 197463, which are incorporated herein by reference. The linker can also be, for example, a linker B or B', or a portion of any one of formulas 20, 2000, 2001, 21, 2100, 2101, 22, 23, 28, or 28a, as described and defined in WO 2005 / 097199, which is incorporated herein by reference. It should be understood that the linker can be connected to the membrane anchor by any suitable chemical bond (linkage) (e.g., by an amide bond or by an ester bond). Similarly, the linker can be connected to the compound of formula (I) (or its pharmaceutically acceptable salt or solvate) by any suitable chemical bond (e.g., by an amide bond or by an ester bond). Although the linker can be connected to any position of the compound of formula (I) or its pharmaceutically acceptable salt or solvate (or to any functional group thereof), it is preferably connected to the substituent R on the group A or the group A. A .

[0069] In addition, the linker and the membrane anchor can together form, for example, any of the moieties described in WO 2017 / 197463 (incorporated herein by reference) to which a PAR-2 ​​inhibitor is attached, or any of the moieties described in WO 2017 / 173347 (incorporated herein by reference) to which a PAR-2 ​​modulating compound is attached, or any of the moieties described in WO 2005 / 097199 (incorporated herein by reference) to which a pharmacophore is attached. Suitable protocols for preparing the corresponding linkers and membrane anchors are also described in these documents.

[0070] An example of a corresponding conjugate, in which the compound of formula (I) is bound to the membrane anchor via a linker, is described in Example 261.

[0071] Therefore, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is bound to a membrane anchor via a linker, wherein the membrane anchor is C 12-20Alkanoyl (e.g., hexadecanoyl, -CO-(CH2) 14 -CH3). The present invention particularly 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-triazaheptatriacontyl)-N-methylpalmitamide or a pharmaceutically acceptable salt or solvate thereof.

[0072] The present invention also relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as a protease-activated receptor 2 (PAR-2) inhibitor in research, in particular as a research tool compound for inhibiting PAR-2. Thus, the present invention relates 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 methods of inhibiting PAR-2, in particular in vitro methods, comprising applying a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. The present invention also relates to methods of inhibiting PAR-2, comprising 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 relates to methods of inhibiting PAR-2 ​​in a sample (e.g., a biological sample), in particular in vitro methods, comprising applying a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof to the sample. The present invention also provides a method for inhibiting PAR-2, the method comprising 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 cellular or subcellular 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 body fluid, or an extract thereof. It should be understood that in this particular context, the term "in vitro" means "outside a living human or animal," and particularly includes experiments conducted with cells, cellular or subcellular extracts, and / or biomolecules in an artificial environment, such as an aqueous solution or culture medium that can be provided, for example, in a flask, test tube, petri dish, microtiter plate, or the like.

[0073] Compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof are described in more detail below.

[0074]

[0075] In formula (I), ring B is a non-aromatic C 4-8 A carbocyclic or non-aromatic 4- to 8-membered heterocyclic ring, wherein the ring B is fused to the ring D, wherein the carbocyclic or heterocyclic ring: (i) is fused to the ring D; 1 (ii) a group R connected to the same ring carbon atom of the carbocyclic ring or the heterocyclic ring 2A and R 2B and (iii) optionally substituted by one or more (eg one, two or three) groups R Y replace.

[0076] Ring D is a 5- or 6-membered heteroaromatic ring, said ring D being fused to ring B, wherein said heteroaromatic ring comprises at least one nitrogen ring atom, wherein said heteroaromatic ring is substituted with a group -LA, and wherein said heteroaromatic ring is optionally substituted with one or more (e.g., one, two, or three) groups R X replace.

[0077] Thus, as shown in formula (I), Ring B and Ring D are fused, i.e., they share two adjacent ring atoms (the two adjacent ring atoms forming part of Ring B and Ring D), thereby forming a fused bicyclic ring system. In the fused bicyclic ring system, only Ring D is aromatic, while Ring B is non-aromatic.

[0078] As mentioned above, ring B is a non-aromatic C 4-8 A carbocyclic or non-aromatic 4- to 8-membered heterocyclic ring, wherein the carbocyclic or heterocyclic ring is optionally substituted by one or more groups R Y It should be understood that ring B is fused to ring D and is replaced by group R 1 substituted by a group R 2A and R 2B (R 2A and R 2B These features are also described in formula (I) and will not be repeated in each case in which Ring B is further described below.

[0079] Preferably, the non-aromatic C 4-8 The carbon ring is C 4-8 Cycloalkyl ring or C 4-8 The cycloalkenyl ring is more preferably C 5-7 Cycloalkyl ring or C 5-7 A cycloalkenyl ring (eg, a cyclohexenyl ring), even more preferably a cyclopentyl ring, a cyclohexyl ring or a cycloheptyl ring.

[0080] Furthermore, preferably, the non-aromatic 4 to 8-membered heterocycle 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, a 3,4-dihydro-2H-pyranyl ring or a 3,6-dihydro-2H-pyranyl ring), even more preferably a 5 to 7-membered heterocycloalkyl ring (e.g., a pyrrolidinyl ring, a piperidinyl ring, a 1,3-diazinanyl ring, a piperazinyl ring, an azepanyl ring, a tetrahydropyranyl ring, a morpholino ring, a 1,4-oxazepanyl ring, or a 1,4-thiaazepanyl ring). In addition, preferably, the non-aromatic heterocycle (also including the heterocycloalkyl ring or the heterocycloalkenyl ring) has one or more (e.g., one or two) ring heteroatoms selected from nitrogen, oxygen, and sulfur, while all remaining ring atoms are carbon atoms, wherein any nitrogen ring atom (if present) and / or any sulfur ring atom (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized (i.e., forming an oxo group). More preferably, the heterocycle (also including the heterocycloalkyl ring or the heterocycloalkenyl ring) has one or more (e.g., one or two) nitrogen ring atoms, while all remaining ring atoms are carbon atoms, wherein one or more carbon ring atoms are optionally oxidized; corresponding examples include, in particular, a pyrrolidinyl ring, a piperidinyl ring, a 1,3-diazacyclohexane ring, a piperazinyl ring, or an azepanyl ring. A particularly preferred example of the heterocycle (or the heterocycloalkyl ring) is a pyrrolidinyl ring.

[0081] Preferably, Ring B is a non-aromatic 4 to 8 membered heterocyclic ring (eg, a 4 to 8 membered heterocycloalkyl ring or a 4 to 8 membered heterocycloalkenyl ring), wherein the heterocyclic ring is optionally substituted by one or more groups R Y More preferably, Ring B is a 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 is optionally substituted by one or more R Y Even more preferably, Ring B is a 5- to 7-membered heterocycloalkyl ring, which is optionally substituted by one or more R Y Even more preferably, Ring B is a 5- to 7-membered heterocycloalkyl ring, which is optionally substituted by one or more R Ysubstituted, wherein the heterocycloalkyl ring has one or two ring heteroatoms (preferably one or two nitrogen ring atoms) selected from nitrogen, oxygen and sulfur, and all remaining ring atoms are carbon atoms, wherein one or more carbon ring atoms are optionally oxidized. Corresponding preferred examples include pyrrolidinyl ring, piperidinyl ring, 1,3-diazacyclohexane ring, morpholinyl ring or azepanyl ring, in particular pyrrolidinyl ring or piperidinyl ring, even more preferably pyrrolidinyl ring. For each of the above preferred definitions of ring B, it is further preferred that ring B contains at least one nitrogen ring atom and the group R 1 Thus, particularly preferred examples of ring B are pyrrolidinyl or piperidinyl rings, wherein the pyrrolidinyl or piperidinyl rings are optionally substituted by one or more R Y substituted, and wherein the group R 1 is connected to the nitrogen ring atom of the pyrrolidinyl ring or the piperidinyl ring. An even more preferred example of ring B is a pyrrolidinyl ring (which is optionally substituted by one or more R Y substituted), wherein the group R 1 is attached to the nitrogen ring atom of the pyrrolidinyl ring.

[0082] According to the above general and preferred definitions of ring B, it is particularly preferred that 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):

[0083]

[0084] It should be understood that the groups of formula (B1), (B2) and (B3) described above are connected by 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 ) between two ring carbon atoms, or C(-R 2A )(-R 2B ) and N(-R 1 ) are fused to Ring D, which is reflected in Formulas (B1), (B2) and (B3) by the bonds extending from these adjacent ring carbon atoms (cut by the wavy lines).

[0085] Y1, Y2 (if present), and Y3 (if 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- are each optionally replaced by one or more groups R Y substituted, wherein the -NH- is optionally replaced by a group R Ysubstituted, and further, wherein one -CH2- unit in the -CH2-CH2- is optionally 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 selection of Y1, Y2 and Y3 in formula (B1) is limited by the additional requirement that the resulting ring B is a 4 to 8-membered ring). In particular, the -CH2- may be optionally replaced by one or two groups R Y and the -CH2-CH2- may be optionally substituted by one, two, three or four groups R Y Substitution. It should be understood that the definitions of Y1, Y2, and Y3 apply only to the presence of these groups in the compound of formula (I), regardless of whether the term "if present" in the definitions of Y1, Y2, and Y3 explicitly reflects this. 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).

[0086] Preferably, Y1, Y2 (if present) and Y3 (if present) are each independently selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, -CO-, and -NH-, wherein said -CH2- and said -CH2-CH2- are each optionally replaced by one or more (e.g., one or two) groups R Y substituted, wherein the -NH- is optionally replaced by a group R Y substituted, and one of the -CH2-CH2- units is optionally replaced by a group selected from -O-, -S-, and -CO-; provided that formula (B1) has 4 to 8 ring atoms. More preferably, Y1, Y2 (if present) and Y3 (if present) are each independently selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, and -CO-, wherein said -CH2- and said -CH2-CH2- are each optionally replaced by one or more (e.g., one or two) groups R Y substituted; provided that formula (B1) has 4 to 8 ring atoms. Even more preferably, Y1, Y2 (if present) and Y3 (if present) are each independently selected from a bond, -CH2-, and -CH2-CH2-, wherein said -CH2- is optionally replaced by one or two groups R Y substituted, and wherein the -CH2-CH2- is optionally substituted by one, two, three or four groups R Y substituted; provided that formula (B1) has 4 to 8 ring atoms.

[0087] In formula (B1), it is particularly preferred that: Y1 is selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, -CO-, and -NH-, wherein said -CH2- and said -CH2-CH2- are each optionally replaced by one or more (e.g., one or two) groups R Y substituted, wherein the -NH- is optionally replaced by a group R Y substituted, and wherein one -CH2- unit of said -CH2-CH2- is optionally replaced by a group selected from -O-, -S-, and -CO-; and Y2 and Y3 are each independently selected from a bond, -CH2-, -O-, -S-, and -CO-, wherein said -CH2- is optionally replaced by one or two groups R Y More preferably, Y1 in formula (B1) is selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, and -CO-, wherein said -CH2- and said -CH2-CH2- are each optionally substituted by one or more (e.g., one or two) groups R Y and Y2 and Y3 in formula (B1) are each independently a bond or -CH2-, wherein the -CH2- is optionally substituted by one or two groups R Y replace.

[0088] In formula (B2), preferably, Y1 and Y2 are each independently selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, -CO-, and -NH-, wherein said -CH2- and said -CH2-CH2- are each optionally replaced by one or more (e.g., one or two) groups R Y substituted, wherein the -NH- is optionally replaced by a group R Y substituted, and one of the -CH2-CH2- units is optionally substituted 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-, wherein the -CH2- and the -CH2-CH2- are each optionally substituted by one or more (e.g., one or two) groups R Y Even more preferably, Y1 and Y2 in formula (B2) are each independently selected from a bond, -CH2-, and -CH2-CH2-, wherein said -CH2- is optionally replaced by one or two groups R Y substituted, and wherein the -CH2-CH2- is optionally substituted by one, two, three or four groups R Y replace.

[0089] In formula (B3), preferably, Y1 is selected from a bond, -CH2-, -CH2-CH2-, -O-, -S-, -CO-, and -NH-, wherein said -CH2- and said -CH2-CH2- are each optionally replaced by one or more (e.g., one or two) groups R Y substituted, wherein the -NH- is optionally replaced by a group R Y substituted, and one of the -CH2-CH2- units in the -CH2- is optionally 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-, wherein the -CH2- and the -CH2-CH2- are each optionally replaced by one or more (e.g., one or two) groups R Y Even more preferably, Y1 in formula (B3) is selected from a bond, -CH2-, and -CH2-CH2-, wherein said -CH2- is optionally replaced by one or two groups R Y substituted, and wherein the -CH2-CH2- is optionally substituted by one, two, three or four groups R Y Even more preferably, Y1 in formula (B3) is -CH2- or -CH2-CH2-, wherein said -CH2- is optionally substituted by one or two groups R Y substituted, and wherein the -CH2-CH2- is optionally substituted by one, two, three or four groups R Y Still more preferably, Y1 in formula (B3) is -CH2-, which is optionally substituted by one or two groups R Y replace.

[0090] Therefore, it is particularly preferred that ring B is a group of the formula:

[0091]

[0092] which are optionally substituted by one or two groups R Y Although the formula (ie, ring B) may be substituted with 0, 1 or 2 groups R Y substituted, but preferably by 0 or 1 groups R Y and more preferably not substituted by any R Y replace.

[0093] Therefore, most preferably, ring B is a group of the formula:

[0094]

[0095] As described above, ring D is a 5- or 6-membered heteroaromatic ring containing at least one nitrogen ring atom, wherein the heteroaromatic ring is optionally substituted by one or more groups R XIt will be understood that ring D is fused to ring B and that ring D is substituted with the group -LA; these features are also described in formula (I) and will not be repeated in each case where ring D is further described below.

[0096] Preferably, ring D is a 5- or 6-membered heteroaromatic ring having one, two or three ring heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein at least one of the ring heteroatoms is a nitrogen ring atom (preferably all the ring heteroatoms are nitrogen ring atoms), while all the remaining ring atoms are carbon atoms, wherein the heteroaromatic ring is optionally substituted by one or more groups R X substituted. Corresponding preferred examples of ring D include pyridyl ring, pyridazinyl ring, pyrimidinyl ring, pyrazinyl ring, 1,2,4-triazinyl ring, 1H-pyrrolyl ring, pyrazolyl ring, imidazolyl ring, 1,2,3-triazolyl ring, furyl ring, thienyl ring, oxazolyl ring, isoxazolyl ring, thiazolyl ring, or isothiazolyl ring. In particular, ring D can be, for example, a 5- or 6-membered heteroaromatic ring comprising one nitrogen ring atom and optionally one further ring heteroatom (preferably further nitrogen ring atom) selected from nitrogen, oxygen and sulfur, wherein all remaining ring atoms are carbon atoms, and wherein the heteroaromatic ring is optionally substituted by one or more radicals R X More preferably, ring D is a 6-membered heteroaromatic ring containing one, two or three nitrogen ring atoms, with all remaining ring atoms being carbon atoms, and wherein the heteroaromatic ring is optionally substituted by one or more groups R X Even more preferably, ring D is a 6-membered heteroaromatic ring comprising one or two nitrogen ring atoms, with all remaining ring atoms being carbon atoms, and wherein the heteroaromatic ring is optionally substituted by one or more groups R X corresponding examples include in particular a pyridyl ring, a pyridazinyl ring, a pyrimidinyl ring, or a pyrazinyl ring. Even more preferably, ring D is a pyridyl or pyrazinyl ring, which is optionally substituted by one or more groups R X Even more preferably, ring D is a pyridyl or pyrazinyl ring, which is optionally substituted by one or more groups R X substituted, wherein the pyridyl or pyrazinyl ring is fused to ring B via its ring carbon atoms 2 and 3. Still more preferably, ring D is a pyrazinyl ring, which is optionally substituted by one or more groups R X substituted, wherein the pyrazinyl ring is fused to ring B via its ring carbon atoms 2 and 3. Furthermore, preferably, ring D is substituted by 0, 1 or 2 groups R X substituted, more preferably by 0 or 1 groups R X Even more preferably, ring D is not substituted by any group R X replace.

[0097] The group -LA is connected to ring D, as also shown in formula (I). Although the group -LA can in principle be connected to any ring atom of ring D (except the two ring atoms shared by ring B and ring D), in the case of a 5-membered heteroaromatic ring as ring D, preferably -LA is connected to the ring atom in the 5-membered heteroaromatic ring that is farthest from the two ring atoms shared by ring B and ring D. In the case of a 6-membered heteroaromatic ring as ring D, preferably -LA is connected to one of the two ring atoms in the 6-membered heteroaromatic ring that are farthest from the two ring atoms shared by ring B and ring D, more preferably, -LA is connected to a ring atom (the ring atom is one of the two ring atoms farthest from the two ring atoms shared by ring B and ring D), the ring atom being closer (i.e., closer) to the ring atom carrying the group R 2A and R 2B A ring atom of Ring B.

[0098] According to the above general and preferred definitions of ring D, it is particularly preferred that ring D is a group of the following formula (D1):

[0099]

[0100] wherein the ring atoms X1, X2, X3 and X4 are each independently a carbon atom or a nitrogen atom, wherein one of X2 and X3 is a carbon atom and carries a group -LA, wherein at least one of the remaining ring atoms of X1, X2, X3 and X4 is a nitrogen atom, and wherein any one of the ring atoms X1, X2, X3 and X4 is a carbon atom (and does not carry a group -LA), which is optionally replaced by a group R X replace.

[0101] It will be understood that the groups of formula (D1) described above are fused to ring B via two adjacent ring carbon atoms (except X1 to X4), which is reflected in formula (D1) by the bonds extending from these adjacent ring carbon atoms (and cut by the wavy line). It will be further understood that if any one of X1, X2, X3 and X4 is fused to ring B via two adjacent ring carbon atoms (except X1 to X4), the fused ring B will be fused to ring B via two adjacent ring carbon atoms (except X1 to X4), which is reflected in formula (D1) by the bonds extending from these adjacent ring carbon atoms (and cut by the wavy line). X substituted carbon atoms, then the group R X Replaces hydrogen atoms, otherwise (ie, no optional substituent R is present X ) wherein the hydrogen atom is attached to the corresponding carbon atom. In addition, it is understood that any one of the ring atoms X1, X2, X3 and X4 is a nitrogen atom which does not carry any optional substituent.

[0102] In formula (D1), preferably, one or two of the ring atoms X1, X2, X3 and X4 are each a nitrogen atom, and all the remaining ring atoms (in X1, X2, X3 and X4) are carbon atoms, wherein one of X2 and X3 is a carbon atom carrying the group -LA. For example, X1 can be a nitrogen atom, while all the remaining ring atoms X2, X3 and X4 are carbon atoms (wherein one of X2 and X3 is a carbon atom carrying the group -LA); or X4 can be a nitrogen atom, while all the remaining ring atoms X1, X2 and X3 are carbon atoms (wherein one of X2 and X3 is a carbon atom carrying the group -LA); or X1 and X4 can be nitrogen atoms, while the remaining ring atoms X2 and X3 are carbon atoms (wherein one of X2 and X3 is a carbon atom carrying the group -LA). 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, wherein one of X2 and X3 is a carbon atom carrying a group -LA. 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, wherein one of X2 and X3 is a carbon atom carrying a group -LA. Still even more preferably, X1 and X4 are each a nitrogen atom and X2 and X3 are each a carbon atom, wherein the carbon atom in X2 or X3 carries a group -LA. As described above, preferably, the compound of formula (I) contains zero, one or two groups R X , more preferably containing zero or one group R X , even more preferably comprising zero (ie no) groups R X Therefore, it is particularly preferred that X1 and X4 are each a nitrogen atom, one of X2 and X3 is C(—LA), and the other of X2 and X3 is C(—H).

[0103] Still more preferably, ring D is a group of the following formula (D2):

[0104]

[0105] wherein the ring atoms X1, X3 and X4 are each independently a carbon atom or a nitrogen atom, wherein at least one of X1, X3 and X4 is a nitrogen atom, and wherein any one of the ring atoms X1, X3 and X4 is optionally replaced by a group R X substituted carbon atoms.

[0106] Preferably, one or two of the ring atoms X1, X3 and X4 are each a nitrogen atom, and all the remaining ring atoms (in 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 can be a nitrogen atom, and X3 and X4 can each be a carbon atom; alternatively, X1 and X3 can each be a nitrogen atom, and X4 can be a carbon atom; alternatively, X1 and X4 can each be a nitrogen atom, and X3 can be a carbon atom. Particularly preferably, X1 and X4 are each a nitrogen atom, and X3 is a carbon atom. As described above, any one of the ring atoms X1, X3 and X4 is optionally replaced by a group R X However, preferably, the compound of formula (I) contains zero, one or two groups R X , more preferably containing zero or one group R X , even more preferably contains zero groups R X , such that any one of the ring atoms X1, X3 and X4 is a carbon atom, which is preferably not replaced by a group R X Therefore, it is particularly preferred that X1 and X4 are each a nitrogen atom, and X3 is optionally replaced by R X substituted carbon atoms; even more preferably, X1 and X4 are each N, and X3 is C(-H).

[0107] Therefore, even more preferably, ring D is a group of formula (D3):

[0108]

[0109] According to the above definitions of rings B and D, it is particularly preferred that the compound of formula (I) has the following structure:

[0110]

[0111] More preferably, the compound of formula (I) has the following structure:

[0112]

[0113] Even more preferably, the compound of formula (I) has the following structure:

[0114]

[0115] Still even more preferably, the compound of formula (I) has the following structure:

[0116]

[0117] Still more preferably, the compound of formula (I) has the following structure:

[0118]

[0119] In formula (I), the group R 1 Selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -(C 0-5 Alkylene)-carbocyclyl, and -(C 0-5 Alkylene) -heterocyclic group, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, and said-(C 0-5 Each alkylene group in the alkylene)-heterocyclyl group is optionally replaced by one or more (eg one, two or three) groups R 12 Substituted, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, or said-(C 0-5 One or more (eg, one, two, or three) -CH2- units contained in the alkylene group in the alkylene group)-heterocyclyl group are each optionally independently selected from -C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, wherein each R L1 are independently hydrogen or C 1-5 Alkyl groups, in which two groups R are attached to the same carbon atom L1 They may also be linked to each other to form, together with the carbon atoms to which they are linked, a cycloalkyl group or a heterocycloalkyl group, and wherein said -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two, three or four) groups R 11 replace.

[0120] Preferably, R 1 Selected from C 1-5 Alkyl, -(C 0-5 Alkylene)-carbocyclyl, and -(C 0-5 Alkylene)-heterocyclic group, wherein the alkyl, the -(C 0-5 Alkylene)-alkylene in carbocyclic group, and said-(C 0-5 The alkylene groups in the heterocyclic group are each optionally substituted by one or more groups R 12 Substituted, wherein the alkyl group, the -(C 0-5 Alkylene)-alkylene in carbocyclic group, or said-(C0-5 One or more -CH2- units contained in the alkylene group in the alkylene)-heterocyclyl group are each optionally independently selected from -C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, wherein each R L1 are independently hydrogen or C 1-5 Alkyl, in which two groups R are attached to the same carbon atom L1 They may also be linked to each other to form a cycloalkyl group (e.g., C 3-6 cycloalkyl) or heterocycloalkyl (e.g., 3- to 6-membered heterocycloalkyl), and wherein the -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R 11 replace.

[0121] More preferably, R 1 Selected from C 1-5 Alkyl (e.g. isobutyl), -(C 0-5 Alkylene)-carbocyclyl, and -(C 0-5 Alkylene)-heterocyclic group, wherein the -(C 0-5 Alkylene)-carbocyclic alkylene and said -(C 0-5 The alkylene groups in the heterocyclic group are each optionally substituted by one or more groups R 12 Substituted, wherein said -(C 0-5 Alkylene)-alkylene in carbocyclic group or said-(C 0-5 One or more -CH2- units contained in the alkylene group in the alkylene)-heterocyclyl group are each optionally independently selected from -C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, wherein each R L1 are independently hydrogen or C 1-5 Alkyl groups, in which two groups R are attached to the same carbon atom L1 They may also be linked to each other to form, together with the carbon atoms to which they are linked, a cycloalkyl group or a heterocycloalkyl group, and wherein said -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R 11 replace.

[0122] Even more preferably, R 1 Yes-L 1 -Carbocyclyl or -L 1 -heterocyclic group, wherein the -L 1 -Carbocyclic group or the -L 1 -heterocyclyl in the heterocyclyl group is optionally substituted by one or more (eg, one, two, three or four) groups R 11 replace.

[0123] For example, R 1 Can be -L 1 Aryl, -L 1 -cycloalkyl, -L 1 -cycloalkenyl, -L 1 -heteroaryl, -L 1 -heterocycloalkyl, or -L 1 -heterocycloalkenyl, wherein the ring portion of each of the above groups is optionally replaced by one or more groups R 11 Particularly preferably, R 1 Yes-L 1 Aryl, -L 1 -cycloalkyl, -L 1 -heteroaryl or -L 1 -heterocycloalkyl, wherein the -L 1 The aryl group in the aryl group, the -L 1 -cycloalkyl in the cycloalkyl group, the -L 1 -heteroaryl in heteroaryl or the -L 1 The heterocycloalkyl group in the heterocycloalkyl group is optionally replaced by one or more groups R 11 More preferably, R 1 Yes-L 1 Aryl, -L 1 -cycloalkyl or -L 1 -heteroaryl, wherein the -L 1 The aryl group in the aryl group, the -L 1 -cycloalkyl in the cycloalkyl group or the -L 1 - The heteroaryl group in the heteroaryl group is optionally replaced by one or more groups R 11 In particular, preferably, R 1 Selected from -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), wherein the ring portion of each of the above groups is optionally replaced by one or more groups R 11 For example, if R 1 Yes-L 1 -heteroaryl [e.g. -L 1 -(monocyclic 5- or 6-membered heteroaryl) or -L 1 -(bicyclic 9- or 10-membered heteroaryl)], wherein the -L 1 - The heteroaryl group in the heteroaryl group is optionally replaced by one or more groups R 11 Substituted, then the -L 1 -heteroaryl can be, for example, selected from 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); Such as, 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, furanyl (e.g., furan-2-yl or furan-3-yl), thienyl (e.g., thien-2-yl or thien-3-yl), oxazolyl (e.g., oxazol-2-yl, oxazol-4-yl, or oxazol-5-yl), 1-yl, 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, benzothiazolyl, benzothiazolyl, benzofuran-6-yl, benzofuran-7-yl, benzofuran-8-yl, benzofuran-9-yl, benzofuran-10-yl, benzofuran-20-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, benzofuran-7-yl, benzofuran-8 ...2 If R 1 Yes-L 1 -cycloalkyl [e.g. -L 1 -(C 3-7 cycloalkyl)], wherein the -L1 -cycloalkyl groups are optionally substituted by one or more groups R 11 Substituted, then the -L 1 The cycloalkyl group in the -cycloalkyl group may, for example, be selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. Even more preferably, R 1 Selected from -L 1 -phenyl, -L 1 -(monocyclic 5- or 6-membered heteroaryl), or -L 1 -(bicyclic 9- or 10-membered heteroaryl), wherein the -L 1 -phenyl in the phenyl group, the -L 1 -(monocyclic 5- or 6-membered heteroaryl) and the -L 1 -(bicyclic 9- or 10-membered heteroaryl) are each optionally substituted by one or more groups R 11 Still even more preferably, R 1 Yes-L 1 -phenyl, wherein the -L 1 The phenyl group in the -phenyl group is optionally substituted by one or more (eg one, two or three) groups R 11 replace.

[0124] R 1 Further examples include the specific groups R contained in the compounds of formula (I) described in the Examples section, especially in any one of Examples 1-282. 1 Any of.

[0125] L 1 independently selected from a bond, --C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, where each R L1 are independently hydrogen or C 1-5 alkyl, and further wherein two groups R attached to the same carbon atom L1 They may also be linked to each other to form a cycloalkyl group (e.g., C 3-6 cycloalkyl) or heterocycloalkyl (e.g., 3- to 6-membered heterocycloalkyl).

[0126] Preferably, L 1 are 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 (C 3-6cycloalkyl-1,1-ene), -O-, -S-, -SO-, -SO2-, -CO-, -NH-, and -N(C 1-5 More preferably, L 1 are 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 are independently selected from a bond, -CH2-, -CH(C 1-3 alkyl)-, and -C(C 1-3 Alkyl)(C 1-3 Still even more preferably, L 1 It is a key.

[0127] According to the above L 1 Definition, particularly preferably, R 1 is optionally substituted by one or more (eg one, two or three) groups R 11 If the phenyl group is optionally substituted by a group R 11 substituted, then preferably, the group R 11 Connected to the meta or para position (preferably the para position) of the phenyl group, that is, R 1 It's 3-R 11 -phenyl or 4-R 11 -phenyl (preferably 4-R 11 -phenyl). If the phenyl group is optionally substituted by two groups R 11 substituted, then preferably, the two groups R 11 Connected at the meta and para positions, i.e. R 1 It's 3-R 11 -4-R 11 -phenyl. If the phenyl group is optionally substituted by three groups R 11 substituted, then preferably, the three groups R 11 The two are connected at the meta position, and a group R 11 Connect in the opposite position, that is, R 1 It's 3-R 11 -4-R 11 -5-R 11 Furthermore, preferably, the phenyl group is surrounded by two or three (especially two) groups R 11 Therefore, it is particularly preferred that R 1 It's 3-R 11 -4-R 11 -phenyl or 3-R 11 -4-R11 -5-R 11 -phenyl, where each R 11 are 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), even more preferably, wherein each R 11 R is independently selected from -F, -Cl, -CF3, and -CH3. 1 Corresponding preferred examples 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. 1 Particularly preferred examples are 4-chloro-3-fluoro-phenyl or 3,4-difluoro-phenyl.

[0128] Each R 11 Independently selected from 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 1-5Alkyl)-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(C1-5 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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two or three) groups R Cyc replace.

[0129] Preferably, each R 11 Independently selected from 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 1-5alkyl), -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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc More preferably, each R 11 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, -(C 0-3 Alkylene)-carbocyclyl, and -(C 0-3 Alkylene)-heterocyclic group, wherein the -(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more independently selected groups selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, halogen, C 1-5 Haloalkyl, -O-(C1-5 Even more preferably, each R 11 Independently selected from C 1-5 Alkyl, halogen, C 1-5 Haloalkyl, -O-(C 1-5 haloalkyl), and -CN. Still even more preferably, each R 11 are independently selected from halogen (e.g., -F, -Cl, -Br, or -I), C 1-5 Haloalkyl (e.g. -CF3), and C 1-5 Still more preferably, each R 11 are independently halogen (especially -F or -Cl) or C 1-5 Haloalkyl (especially -CF3).

[0130] Each R 12 Independently selected from -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(C1-5 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), carbocyclyl, heterocyclyl, and -L Z -R Z wherein the carbocyclyl and the heterocyclyl are each optionally substituted by one or more (eg one, two or three) groups R Cyc replace.

[0131] Preferably, each R 12 Independently selected from -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 1-5alkyl), -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 More preferably, each R 12 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.

[0132] R 2A and R 2B are linked to each other to form, together with the carbon atoms to which they are attached, a cycloalkyl, a cycloalkenyl, a heterocycloalkyl, or a heterocycloalkenyl, wherein the cycloalkyl, the cycloalkenyl, the heterocycloalkyl or the heterocycloalkenyl is optionally substituted by one or more (e.g., one, two or three) groups R 21 Replace; or, R 2A and R 2B Each independently selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -(C 0-5 Alkylene)-carbocyclyl, and -(C 0-5 Alkylene) -heterocyclic group, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, and said-(C 0-5 The alkylene groups in the heterocyclic group are each optionally substituted by one or more groups R22 Substituted, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, or said-(C 0-5 The one or more -CH2- units contained in the alkylene in the alkylene)-heterocyclyl are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, wherein the -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc Substituted, where R 2A and group R Y (if present) may also be linked to each other to form, together with the ring atoms to which they are attached, a carbocyclyl or a heterocyclyl, wherein said carbocyclyl or said heterocyclyl is optionally substituted by one or more (e.g. one, two or three) groups R Cyc replace.

[0133] As mentioned above, R 2A and R 2B can be linked to each other to form, together with the carbon atoms to which they are linked, a cycloalkyl, a cycloalkenyl, a heterocycloalkyl or a heterocycloalkenyl group, wherein the cycloalkyl, the cycloalkenyl, the heterocycloalkyl or the heterocycloalkenyl group is optionally substituted by one or more groups R 21 It should be understood that the cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl together with the fused ring B and ring D form a spiro ring system. 2A 、R 2B and carry R 2A and R 2B is preferably a monocyclic cycloalkyl, more preferably C 3-7 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl); a particularly preferred example of the cycloalkyl is cyclopentyl. The cycloalkenyl (which consists of R 2A 、R 2B and carry R 2A and R 2B is preferably a monocyclic cycloalkenyl group, more preferably C 4-7 Cycloalkenyl (e.g., cyclobutenyl, cyclopentenyl, cyclohexenyl, or cycloheptenyl); particularly preferred examples of the cycloalkenyl are cyclobutenyl or cyclopentenyl. 2A 、R 2B and carry R 2A and R 2BThe heterocycloalkyl radical is preferably a monocyclic heterocycloalkyl radical, more preferably a 3- to 7-membered heterocycloalkyl radical (e.g. containing one or two ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein all remaining ring atoms are carbon atoms), even more preferably a 4- to 7-membered heterocycloalkyl radical having one ring heteroatom selected from oxygen, sulfur and nitrogen (wherein all other ring atoms are carbon atoms); corresponding examples of such heterocycloalkyl radicals include tetrahydrofuranyl (which may be attached via, for example, a carbon ring atom at position 3), tetrahydropyranyl (which may be attached via, for example, a carbon ring atom at position 4), tetrahydrothienyl (which may be attached via, for example, a carbon ring atom at position 3), thianyl (which may be attached via, for example, a carbon ring atom at position 4), pyrrolidinyl (which may be attached via, for example, a carbon ring atom at position 3), or piperidinyl (which may be attached via, for example, a carbon ring atom at position 4); a particularly preferred example of such heterocycloalkyl radicals is tetrahydrofuranyl (which may be attached via, for example, a carbon ring atom at position 3). The heterocycloalkenyl radical (which is composed of R 2A 、R 2B and carry R 2A and R 2B ) is preferably a monocyclic heterocycloalkenyl group, more preferably a 4- to 7-membered heterocycloalkenyl group (e.g. containing one or two ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein all remaining ring atoms are carbon atoms), even more preferably a 4- to 7-membered heterocycloalkenyl group having one ring heteroatom selected from oxygen, sulfur and nitrogen (wherein all remaining ring atoms are carbon atoms). Particularly preferably, R 2A and R 2B are linked to each other to form, together with the carbon atoms to which they are attached, a cycloalkyl group or a heterocycloalkyl group, wherein the cycloalkyl group or the heterocycloalkyl group is optionally substituted by one or more groups R 21 Even more preferably, R 2A and R 2B are linked to each other to form, together with the carbon atoms to which they are attached, a cyclopentyl or tetrahydrofuranyl group, wherein the cyclopentyl or tetrahydrofuranyl group is optionally substituted by one or more groups R 21 substituted (still even more preferably, R 2A and R 2B are linked to each other so as to form, together with the carbon atoms to which they are attached, a cyclopentyl group, which is optionally substituted by one or more groups R 21 substituted); therefore, according to the above preferred definitions of ring B and ring D, it is particularly preferred that the compound of formula (I) has one of the following structures:

[0134]

[0135] wherein the cyclopentyl ring and the tetrahydrofuranyl ring in the above formula are each optionally substituted by one or more groups R 21In this case, according to the above preferred definitions of ring B and ring D, even more preferably, the compound of formula (I) has one of the following structures:

[0136]

[0137] wherein the cyclopentyl ring and the tetrahydrofuranyl ring in the above formula are each optionally substituted by one or more groups R 21 substituted; yet even more preferably, the compound of formula (I) has the following structure:

[0138]

[0139] wherein the cyclopentyl ring in the above formula is optionally replaced by one or more groups R 21 replace.

[0140] Or (i.e., if R 2A and R 2B are not connected to each other), the group R 2A and R 2B Each independently selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -(C 0-5 Alkylene)-carbocyclyl, and -(C 0-5 Alkylene) -heterocyclic group, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, and said-(C 0-5 Each alkylene group in the alkylene)-heterocyclyl group is optionally replaced by one or more (eg one, two or three) groups R 22 Substituted, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, or said-(C 0-5 The one or more (e.g., one, two, or three) -CH2- units contained in the alkylene group in the alkylene group)-heterocyclyl group are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, wherein the -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclic group in the alkylene)-heterocyclic group is optionally replaced by one or more (eg one, two or three) groups R Cyc replace.

[0141] If R 2A and R 2B Not connected to each other, preferably, R 2A and R2B Each independently selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -(C 0-5 Alkylene)-carbocyclyl, and -(C 0-5 Alkylene) -heterocyclic group, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, and said-(C 0-5 Each alkylene in the alkylene)-heterocyclyl is optionally replaced by one or more (eg, one, two, or three) 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, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, or said-(C 0-5 The one or more (e.g., one, two, or three) -CH2- units contained in the alkylene group in the alkylene group)-heterocyclyl group are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, wherein the -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two or three) groups R Cyc More preferably, R 2A and R 2B 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, wherein the alkyl or the -(C 0-5 Alkylene)-cycloalkyl, said-(C 0-5 Alkylene)-aryl, said-(C 0-5 Alkylene)-heterocycloalkyl, or said-(C 0-5 The alkylene in any one of the heteroaryl) groups is optionally replaced by one or more independently selected from -OH, -O(C1-5 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, wherein the alkyl or the -(C 0-5 Alkylene)-cycloalkyl, said-(C 0-5 Alkylene)-aryl, said-(C 0-5 Alkylene)-heterocycloalkyl, or said-(C 0-5 The one or more -CH2- units contained in any one of the alkylene groups in the heteroaryl group are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-; and further, wherein said -(C 0-5 Alkylene) -cycloalkyl in the cycloalkyl, the -(C 0-5 alkylene) aryl, the aryl group in the -(C 0-5 Alkylene) -heterocycloalkyl in heterocycloalkyl, and said -(C 0-5 The heteroaryl groups in the alkylene)-heteroaryl groups are each optionally substituted by one or more groups R Cyc Even more preferably, R 2A and R 2B Each independently selected from C 1-5 Alkyl, -(C 0-5 Alkylene)-cycloalkyl, -(C 0-5 Alkylene)-aryl (e.g., -(C 0-5 Alkylene)-phenyl, such as -CH2-phenyl), -(C 0-5 alkylene)-heterocycloalkyl, and -(C 0-5 alkylene)-heteroaryl, wherein the alkyl or the -(C 0-5 Alkylene)-cycloalkyl, said-(C 0-5 Alkylene)-aryl, said-(C 0-5 Alkylene)-heterocycloalkyl, or said-(C 0-5 The alkylene in any one of the heteroaryl) groups is optionally replaced by one or more 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, C1-5 Haloalkyl, -O-(C 1-5 haloalkyl), and -CN, and further, wherein the -(C 0-5 Alkylene) -cycloalkyl in the cycloalkyl, the -(C 0-5 alkylene) aryl, the aryl group in the -(C 0-5 Alkylene) -heterocycloalkyl in heterocycloalkyl, and said -(C 0-5 The heteroaryl groups in the alkylene)-heteroaryl group are each optionally substituted by one or more independently selected groups 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 Still more preferably, R 2A and R 2B Each independently selected from C 1-5 Alkyl, -(C 0-3 Alkylene)-cycloalkyl (e.g., cyclopropyl, -CH2-cyclopropyl, cyclobutyl, -CH2-cyclobutyl, cyclopentyl, or -CH2-cyclopentyl), -(C 0-3 -(C 2-alkylene)-heterocycloalkyl [e.g., oxetanyl (such as oxetan-2-yl or oxetan-3-yl), -CH 2 -oxetanyl (such as oxetan-2-ylmethyl or oxetan-3-ylmethyl), tetrahydrofuranyl (such as tetrahydrofuran-3-yl), -CH 2 -tetrahydrofuranyl (such as tetrahydrofuran-3-ylmethyl), tetrahydropyranyl (such as tetrahydropyran-4-yl), or -CH 2 -tetrahydropyranyl (such as tetrahydropyran-4-ylmethyl)], or -(C 0-3 -C(-CH)(-CH)-pyridinyl (such as -C(-CH)(-CH)-(pyridin-2-yl)), -CH-pyrimidinyl (such as pyrimidin-2-ylmethyl), -CH-pyrazinyl (such as pyrazin-2-ylmethyl)], wherein the alkyl group is optionally substituted by one or more independently selected from -OH, -O(C 1-5 alkyl), -SH, -S(C 1-5alkyl), -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, wherein the -(C 0-3 Alkylene) -cycloalkyl in the cycloalkyl, the -(C 0-3 The heterocycloalkyl group in the -(C 0-3 The heteroaryl groups in the alkylene)-heteroaryl group are each optionally substituted by one or more independently selected groups 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. Thus, for example, R 2A and R 2B Each is independently C 1-5 Alkyl, which is optionally substituted by one or more 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; R 2A and / or R 2B The corresponding preferred example is C 1-5 Alkyl (e.g. tert-butyl) which is replaced by one or two groups -O(C 1-5 R is substituted with -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. 2A and / or R 2B Another example is -(C 0-3 alkylene)-phenyl, which is optionally substituted by one or more independently selected from C1-5 Alkyl, halogen, C 1-5 Haloalkyl, -O-(C 1-5 substituted with -(4-chloro-3-fluorophenyl)-4-chloro-3-fluorophenylmethyl. Thus, for example, R 2A can be 4-chloro-3-fluorophenyl and R 2B Can be C 1-5 Alkyl (eg methyl). 2A and R 2B Particularly preferred examples of each include 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-C H3 (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-(cyclobutane-1,3-diyl)-CH2-O-CH3, pyridin-2-ylmethyl, 6-methoxypyridin-2-ylmethyl, or 1-methyl-1-(pyridin-2-yl)ethyl. Still more preferably, R 2A and R 2B Each is independently C 1-5 Therefore, as a particularly preferred example, R 2A and R 2B It should be understood that for the R 2A and R 2B In each of the general and preferred definitions of 2A and R 2B Can be the same or different.

[0142] Furthermore, as mentioned above, the group R 2A It can also be combined with the group R Y Connect to each other (if there is R Y ; preferably connected to and carrying R 2A The group R on the ring atom directly adjacent to the carbon ring atom of Y connected to each other) to form a 2A and R Y The attached ring atoms together form a carbocyclyl or heterocyclyl, wherein the carbocyclyl or heterocyclyl is optionally substituted by one or more (eg one, two or three) groups RCyc In particular, the group R 2A Can be combined with group R Y (if present) are linked to each other, wherein the groups R Y With R 2A The carbon ring atom of the group R is directly adjacent to the ring atom. 2A and R Y The linked ring atoms together form a carbocyclyl or heterocyclyl, wherein the carbocyclyl or heterocyclyl is optionally substituted by one or more groups R Cyc It is understood that the corresponding carbocyclyl or heterocyclyl is thus fused to ring B, which together with ring D forms a fused tricyclic ring system. 2A and R Y (and these groups R 2A and R Y The carbocyclic group formed by the ring atoms to which the group is attached can be, for example, a cycloalkyl, a cycloalkenyl or an aryl; preferably, the carbocyclic group is a cycloalkyl, such as a cyclopentyl or a cyclohexyl. 2A and R Y (and these groups R 2A and R Y The heterocyclic group formed by the ring atoms connected to the ring can be, for example, heterocycloalkyl, heterocycloalkenyl or heteroaryl; preferably, the heterocyclic group is heterocycloalkyl, such as, for example, tetrahydrofuranyl (which can be connected through, for example, the ring carbon atoms in the 2 and 3 positions). Thus, if R 2A and group R Y (Preferably with R 2A The carbon ring atom of the group R is directly connected to the adjacent ring atom Y ) are linked to each other, then particularly preferably, they are linked to each other so as to form, together with the ring atoms to which they are linked, a cycloalkyl group or a heterocycloalkyl group, wherein the cycloalkyl group or the heterocycloalkyl group is optionally substituted by one or more radicals R Cyc It should be understood that if R 2A and group R Y interconnected, the groups R 2B Has the same meaning as above (see R 2A and R 2B R when not connected to each other 2B general and preferred meanings of ).

[0143] Each R 21 Independently selected from 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), -(C0-3 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(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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two or three) groups R Cyc replace.

[0144] Preferably, each R 21 Independently selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -OH, -O(C1-5 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 group, -(C 0-3alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc More preferably, each R 21 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, -(C 0-3 Alkylene)-carbocyclyl, and -(C 0-3 Alkylene)-heterocyclic group, wherein the -(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more independently selected groups selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, halogen, C 1-5 Haloalkyl, -O-(C 1-5 Even more preferably, each R 21 Independently selected from 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.

[0145] Each R 22 Independently selected from -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(C1-5 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), carbocyclyl, heterocyclyl, and -L Z -R Z wherein the carbocyclyl and the heterocyclyl are each optionally substituted by one or more (eg one, two or three) groups R Cyc replace.

[0146] Preferably, each R 22 Independently selected from -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 1-5Alkyl), -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 More preferably, each R 22 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.

[0147] Each R X Independently selected from C1-5 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-(C1-5 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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two or three) groups R Cycreplace.

[0148] Preferably, each R X Independently selected from 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-(C1-5 alkyl), -SO-(C 1-5 alkyl), -SO2-(C 1-5 Alkyl), -(C 0-3 Alkylene)-carbocyclic group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc More preferably, each R X 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), -CN, -(C 0-3 alkylene)-cycloalkyl (e.g., cyclopropyl), and -(C 0-3 alkylene)-heterocycloalkyl, wherein the -(C 0-3 The cycloalkyl group in the alkylene)-cycloalkyl group and the -(C 0-3 The heterocycloalkyl groups in the alkylene)-heterocycloalkyl groups are each optionally substituted by one or more groups R Cyc replace.

[0149] Each R Y Independently selected from 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 0-3Alkylene)-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 1-5alkyl)-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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two or three) groups R Cyc replace;

[0150] Any two groups R attached to the same ring carbon atom Y The (i) radicals (if present) may also be linked to each other to form, together with the ring atoms to which they are linked, a cycloalkyl radical or a heterocycloalkyl radical, wherein said cycloalkyl radical or said heterocycloalkyl radical is optionally substituted by one or more (e.g. one, two or three) radicals R Cyc substitution, or (ii) may mutually form a group =0.

[0151] Preferably, each R Y Independently selected from C 1-5 Alkyl, -(C 0-3 Alkylene)-OH, -(C 0-3 Alkylene)-O(C 1-5 Alkyl), -(C 0-3 Alkylene)-SH, -(C0-3 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 0-3Alkylene)-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 (eg, pyridinyl; such as pyridin-2-yl), and -(C 0-3 alkylene)-heterocycloalkyl, wherein the -(C 0-3 alkylene) aryl, the aryl group in the -(C 0-3 Alkylene) -cycloalkyl in the cycloalkyl, the -(C 0-3 The heteroaryl in the alkylene)-heteroaryl, and the -(C 0-3 The heterocycloalkyl groups in the alkylene)-heterocycloalkyl groups are each optionally substituted by one or more groups R Cyc substituted; wherein any two groups R attached to the same ring carbon atom Y (i) (if present) may also be linked to each other to form, together with the carbon atoms to which they are attached, a cycloalkyl group (e.g. C 3-7 cycloalkyl) or heterocycloalkyl (e.g., 3- to 7-membered heterocycloalkyl), wherein the cycloalkyl or heterocycloalkyl is optionally substituted by one or more groups R Cyc or (ii) can mutually form a group =O. More preferably, each R Y 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 Furthermore, preferably, ring B is surrounded by 0, 1, 2 or 3 groups R Y substituted, more preferably by 0, 1 or 2 groups R Y substituted, even more preferably by 0 or 1 groups R Y Even more preferably, ring B is not substituted by any group R Y replace.

[0152] The group L is selected from -CO-, -SO- and -SO2-. Preferably, L is -CO- or -SO2-. More preferably, L is -CO-.

[0153] Group A is -N(-R N )-R N or a heterocyclic group, wherein the heterocyclic group is linked to the group L via a ring nitrogen atom, and wherein the heterocyclic group is optionally substituted by one or more (e.g., one, two, three, or four) groups R A replace.

[0154] Each R N are independently selected from 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 1-5Alkyl)(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(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)-carbocyclyl, and -(C 0-8 Alkylene)-heterocyclic group, wherein the C 1-8 Alkyl, the C 2-8 Alkenyl, the C 2-8 Alkynyl, and the above C 0-8 Alkylene and C 1-8 The one or more (eg, one, two, or three) -CH2- units contained in any one of the alkylene groups are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, wherein the -(C 0-8 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-8The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two or three) groups R Cyc substituted, and wherein at least one group R N Not hydrogen.

[0155] Preferably, each R N are independently selected from 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 1-5 Alkyl), -(C 1-5 Alkylene)-NH-CO-(C 1-5 Alkyl), -(C 1-5 Alkylene)-N(C 1-5 alkyl)-CO-(C 1-5Alkyl), -(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)-heterocyclic group, wherein the C 1-5 Alkyl, the C 2-5 Alkenyl, the C 2-5 Alkynyl, and the above C 0-5 Alkylene and C 1-5 The one or more (eg, one, two, or three) -CH2- units contained in any one of the alkylene groups are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, wherein the -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two or three) groups R Cyc substituted, and wherein at least one group R N Not hydrogen.

[0156] As mentioned above, if the group A is -N(-R N)-R N , then 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 , where R N Selected from 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), -(C1-5 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)-heterocyclic group, wherein the C 1-5 Alkyl, the C 2-5 Alkenyl, the C 2-5 Alkynyl, and the above C 0-5 Alkylene and C 1-5 The one or more (eg, one, two, or three) -CH2- units contained in any one of the alkylene groups are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, wherein the -(C 0-5 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-5 The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two or three) groups R CycCorresponding preferred examples of group A include -NH-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxyl-4,6-dimethyl-pyridin-2-yl), -NH-C(-CH3)(-CH3)-CH2-N(-CH3)-(5-carboxyl-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)cyclopropane-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-carboxyl-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)cyclopropane-1-yl),-N[-(C 1-5 Alkylene)-O(C 1-5alkyl)]-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-carboxyl-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 1-5 alkyl)]-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 1-5alkyl)]-(1-(aminocarbonyl)cyclopropane-1-yl). Particularly preferred examples of group A include -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)-CH 2-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-CH2-CH(-CH3)-CH2-COOH, -N(-CH3)-CH2-CH2-CH(-CH3)-CH2-CO-NH2, -N(-CH3)-CH2-CH2-CH(-CH3)-CH2-CO-N(-CH3)-CH3, or -NH-(1-(aminocarbonyl)cyclopropane-1-yl).

[0157] Preferably, group A is a heterocyclic group connected to group L via a ring nitrogen atom, and wherein the heterocyclic group is optionally substituted by one or more groups R A The heterocyclyl group may be, for example, a 5- to 14-membered heterocyclyl group. More preferably, group A is a heterocycloalkyl or heterocycloalkenyl group, wherein the heterocycloalkyl or heterocycloalkenyl group is connected to group L via a ring nitrogen atom, and wherein the heterocycloalkyl or heterocycloalkenyl group is optionally substituted by one or more groups R A The heterocycloalkyl or heterocycloalkenyl group may be, for example, a 5- to 14-membered heterocycloalkyl or a 5- to 14-membered heterocycloalkenyl group. Even more preferably, group A is a heterocycloalkyl group connected to group L via a ring nitrogen atom, wherein the heterocycloalkyl group is optionally substituted by one or more groups R ASubstitution.Described heterocycloalkyl is preferably 5 to 11 yuan of heterocycloalkyl, it contains a nitrogen-ring atom (heterocycloalkyl is connected with group L by described nitrogen-ring atom) and optionally contains one or more (such as one, two or three) other ring heteroatoms independently selected from nitrogen, oxygen and sulphur, wherein all remaining ring atoms are carbon atoms, wherein any nitrogen-ring atom (if present) and / or any sulphur ring atom (if present) are optionally oxidized, and wherein one or more carbocyclic atoms are optionally oxidized (i.e. forming oxo group).More preferably, described heterocycloalkyl is 5 to 7 yuan (even more preferably, 6-yuan) monocyclic heterocycloalkyl, it contains a nitrogen-ring atom (heterocycloalkyl is connected with group L by described nitrogen-ring atom) and optionally contains one or two other ring heteroatoms independently selected from nitrogen, oxygen and sulphur, wherein all remaining ring atoms are carbon atoms, wherein any nitrogen-ring atom (if present) and / or any sulphur ring atom (if present) are optionally oxidized, and wherein one or more carbocyclic atoms are optionally oxidized. Furthermore, the heterocycloalkyl group may contain a lactam functionality, i.e. the heterocycloalkyl group may contain a second nitrogen ring atom adjacent to the oxidized carbon ring atom (C=O) (except for the first nitrogen ring atom via which the group A is linked to the group L). A corresponding preferred example of the group A is 3-oxopiperazin-1-yl, which is optionally substituted by one or more (e.g. one, two, three or four) groups R A Substituted; a particularly preferred example of a corresponding group A is 2,2-dimethyl-piperazin-3-one-1-yl (which may optionally be further substituted with one or more R A A further preferred example of group A is 4-(5-carboxypyridin-2-yl)piperazin-1-yl, which is optionally substituted with one or more (e.g. one, two, three or four) groups R A Substituted; corresponding preferred examples of group A include 2,2-dimethyl-4-(5-carboxyl-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl or 2,2-dimethyl-4-(5-carboxyl-pyridin-2-yl)piperazin-1-yl (each of which may be optionally further substituted by one or more R A substituted), in particular 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl. A further preferred example of group A is 4-(5-carboxymethylpyridin-2-yl)piperazin-1-yl, which is optionally substituted by one or more (e.g. one, two, three or four) groups R A Substituted; corresponding preferred examples of group A include 2,2-dimethyl-4-(5-carboxymethylpyridin-2-yl)piperazin-1-yl (which may optionally be further substituted with one or more R AFurther preferred examples of group A are 4-(4-carboxythiazol-2-yl)piperazin-1-yl or 4-(5-carboxythiazol-2-yl)piperazin-1-yl, each of which is optionally substituted with one or more (e.g., one, two, three or four) groups R A Substituted; 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 of which may be further optionally substituted by one or more R A A further preferred example of group A is 4-(carboxymethyl)piperidin-1-yl, which is optionally substituted with one or more (eg one, two, three or four) groups R A Substituted; 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 of which may be optionally further substituted by one or more R A replace).

[0158] Further examples of group A include any of the specific groups A contained in the compounds of formula (I) described in the Examples section, in particular any of Examples 1-282.

[0159] Each R A Independently selected from 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), -(C0-3 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)(C1-5 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 group, -(C 0-3 alkylene)-heterocyclyl, and -L Z -R Z wherein said-(C 0-3 Alkylene) -carbocyclic group and the carbocyclic group - (C 0-3 The heterocyclyl groups in the alkylene)-heterocyclyl group are each optionally substituted by one or more (eg one, two or three) groups R Cyc and further, wherein any two groups R connected to the same carbon atom of group A are A They may also be linked to each other to form, together with the carbon atoms to which they are attached, a cycloalkyl group or a heterocycloalkyl group, wherein the cycloalkyl group or the heterocycloalkyl group is optionally substituted by one or more (e.g. one, two or three) groups R Cyc replace.

[0160] Preferably, each R A Independently selected from 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), -(C0-3 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 1-5alkyl)-SO2-(C 1-5 Alkyl), -(C 0-3 Alkylene) aryl, -(C 0-3 Alkylene)-cycloalkyl (e.g. cyclopropyl), -(C 0-3 alkylene)-heteroaryl (eg, pyridinyl; such as pyridin-2-yl), and -(C 0-3 alkylene)-heterocycloalkyl, wherein the -(C 0-3 alkylene) aryl, the aryl group in the -(C 0-3 Alkylene) -cycloalkyl in the cycloalkyl, the -(C 0-3 The heteroaryl in the alkylene)-heteroaryl, and the -(C 0-3 The heterocycloalkyl groups in the alkylene)-heterocycloalkyl groups are each optionally substituted by one or more groups R Cyc and further, wherein any two groups R attached to the same carbon atom of group A are A They may also be linked to each other to form a cycloalkyl group (e.g., C 3-7 cycloalkyl, such as cyclopropyl).

[0161] If the group A is a heterocyclic group (as described above, including any corresponding preferred or exemplary cyclic group A described herein; hereinafter referred to as "ring A"), it is particularly preferred that at least two substituents R are present. A , which are attached to the same carbon ring atom of Ring A, and which are each independently C 1-5 Alkyl groups, or they are linked together with the carbon ring atoms to which they are linked to form C 3-7 Thus, it is particularly preferred that group A is a heterocycloalkyl group (including any of the specific heterocycloalkyl groups described above) connected to group L via a ring nitrogen atom, wherein the heterocycloalkyl group (i) is connected to the same ring carbon atom by two C 1-5 Alkyl substituted or (ii) two substituents R attached to the same ring carbon atom A Substituted, and the two substituents R A are linked to each other to form, together with the ring carbon atoms to which they are attached, C 3-7 Cycloalkyl (eg cyclopropyl), and wherein the heterocycloalkyl is optionally further substituted by one or more groups R A Even more preferably, group A is a heterocycloalkyl group (including any of the specific heterocycloalkyl groups described above) connected to group L via a ring nitrogen atom, wherein the heterocycloalkyl group is connected to two C 1-5 wherein the heterocycloalkyl group is optionally further substituted with one or more groups R A Substituted (e.g. by a group R A Substituted, the group RA is 5-carboxy-4,6-dimethyl-pyridin-2-yl). Two C 1-5 The alkyl groups may be the same or different and are preferably independently selected from methyl, ethyl, propyl and butyl; more preferably, two C 1-5 Alkyl is each methyl. 3-7 Cycloalkyl (which consists of two substituents R A Formed) is preferably selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; more preferably, C 3-7 Cycloalkyl is cyclopropyl. Two C 1-5 Alkyl or two substituents R connected to each other A (Together they form C 3-7 The position where the cycloalkyl group is attached, i.e., the specific carbon atoms of ring A, is not particularly limited. For example, two C 1-5 Alkyl or two substituents R connected to each other A (Together they form C 3-7 The cycloalkyl group) may be attached to a carbon ring atom (of ring A) which is (i) directly adjacent to a nitrogen ring atom through which ring A is attached to group L, or (ii) separated from the nitrogen ring atom by one ring atom (through which ring A is attached to group L), or (iii) separated from the nitrogen ring atom by two ring atoms (through which ring A is attached to group L). Corresponding preferred examples of ring A include 2,2-dimethyl-piperazin-1-yl, 3,3-dimethyl-piperazin-1-yl, 2,2-dimethyl-piperazin-3-on-1-yl, 2,2,4-trimethyl-piperazin-3-on-1-yl, 4-ethyl-2,2-dimethyl-piperazin-3-on-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[piperidin-2,1'-cyclopropane]-1-yl, spiro[piperidin-3,1'-cyclopropane]-1-yl, or spiro[piperidin-4,1'-cyclopropane]-1-yl, wherein the piperazinyl portion, piperazinone (piperazinonyl) portion or piperidinyl portion of each of the above groups is optionally further replaced by one or more (e.g., one or two) groups R A Substituted (e.g. by a group R A Substituted, the group R A is 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). Particularly preferably, two C 1-5Alkyl or two substituents R connected to each other A (Together they form C 3-7 A cycloalkyl group, preferably a cyclopropyl group) is attached to a carbon ring atom which is directly adjacent to a nitrogen ring atom via which ring A is attached to group L. A corresponding particularly preferred example of ring A is 2,2-dimethyl-piperazin-1-yl, wherein the piperazinyl group in the 2,2-dimethyl-piperazin-1-yl group is optionally further substituted by one or more groups R A substituted; thus, Ring A can 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.

[0162] According to the above, it is particularly preferred that group A is selected from any one of the following groups:

[0163] (For example (For example (For example

[0164] A particularly preferred example of group A is 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl:

[0165]

[0166] 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-carboxyl-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl, and R 2A and R 2B are linked to each other to form C 3-7 Cycloalkyl (preferably cyclopentyl), the C 3-7 The cycloalkyl group is optionally substituted by one or more groups R 21The 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-carboxyl-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl, and R 2A and R 2B Each is independently C 1-5 Alkyl (such as R 2A and R 2B each may be methyl).

[0167] Another particularly preferred example of group A is 3-methoxy-4-(carboxymethyl)piperidin-1-yl:

[0168] (For example ).

[0169] 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 Each is independently C 1-5 Alkyl (such as R 2A and R 2B each may be methyl).

[0170] Another particularly preferred example of group A is 2,2-dimethyl-3-oxo-piperazin-1-yl:

[0171]

[0172] The present invention particularly relates to compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein group A is 2,2-dimethyl-3-oxo-piperazin-1-yl and R 2A and R 2B Each is independently C 1-5 Alkyl (such as R 2A and R 2B each may be methyl).

[0173] Each R Cyc Independently selected from 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(C1-5 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 Halogenated alkyl), -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)(-OC 1-5 alkyl), -P(=O)(-OC 1-5 Alkyl)(-OC 1-5 Alkyl), -(C 0-3 Alkylene)-cycloalkyl, -(C 0-3 alkylene)-heterocycloalkyl, and -L Z -R Z .

[0174] Preferably, each R Cyc Independently selected from 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 Halogenated alkyl), -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-(C1-5 alkyl), -SO-(C 1-5 Alkyl), -(C 0-3 Alkylene)-cycloalkyl, -(C 0-3 alkylene)-heterocycloalkyl, and -L Z -R Z More preferably, each R Cyc Independently selected from C 1-5 Alkyl, -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.

[0175] Each L Z independently selected from covalent bonds, C 1-7 Alkylene, C 2-7 Alkenylene, and C 2-7 wherein the alkylene, the alkenylene and the alkynylene are each optionally substituted by one or more (e.g., one, two or three) 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) group, and further, wherein the one or more (e.g., one, two or three) -CH2- units contained in the alkylene, the alkenylene or the alkynylene are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2- groups.

[0176] Preferably, each L Z independently selected from covalent bonds, C 1-5 Alkylene, C 2-5 Alkenylene, and C 2-5wherein the alkylene, the alkenylene and the alkynylene are each optionally substituted by one or more (e.g., one, two or three) 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) group, and further, wherein the one or more (e.g., one, two or three) -CH2- units contained in the alkylene, the alkenylene or the alkynylene are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2- groups.

[0177] Each R Z Independently selected from -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 Halogenated alkyl), -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(C1-5 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, each of which is optionally substituted by one or more (e.g., one, two or three) 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), -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 1-5alkyl), -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), carbocyclyl, and heterocyclyl, wherein the carbocyclyl and the heterocyclyl are each optionally substituted by one or more independently selected 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 1-5alkyl), and -SO2-(C 1-5 alkyl) groups.

[0178] Preferably, each R Z Independently selected from -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 Halogenated alkyl), -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-(C1-5 alkyl), -SO-(C 1-5 alkyl), aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, wherein the aryl, the heteroaryl, the cycloalkyl and the heterocycloalkyl are each optionally substituted by one or more (e.g., one, two or three) 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), -NH2, -NH(C 1-5 alkyl), and -N(C 1-5 Alkyl)(C 1-5 alkyl) groups.

[0179] Preferably, at least one (more preferably all) of the following conditions apply to the compounds of formula (I):

[0180] – If Ring B is a pyrrolidinyl ring and Ring D is a pyridyl ring, R 2A and R 2B are linked to each other to form a cyclopropyl group together with the carbon atoms to which they are attached, L is -CO-, and group A is morpholin-4-yl, then R 1 Not 5-R 11 -pyrimidin-2-yl or acetyl; and / or

[0181] – If 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 Each is methyl, R 1 is optionally replaced by one or more groups R 11 Substituted phenyl, L is -CO-, and group A is -NH-R N , then R N is not a heterocycloalkyl group containing one oxidized sulfur ring atom, wherein all other ring atoms are carbon atoms, and said heterocycloalkyl group is substituted with methyl; and / or

[0182] – If ring B and ring D together form 3-R X -4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring, R X is -OH, R 2A and R 2B One of them is a methyl group, R2A and R 2B The other one is -CON(-CH3)2, R 1 is methyl, L is -CO-, and group A is -NH-R N , then R N is not 4-fluorobenzyl; and / or

[0183] – If 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 group A is -NH-R N , and R 1 is -CH2-phenyl or -CH2-pyridyl, wherein the phenyl group in the -CH2-phenyl group and the pyridyl group in the -CH2-pyridyl group are each optionally substituted by one or more groups R 11 Substitution, then R 2A and R 2B Not meth.

[0184] Thus, as mentioned above, preferably, the following conditions apply to compounds of formula (I): if ring B is a pyrrolidinyl ring, ring D is a pyridyl ring, R 2A and R 2B are linked to each other to form a cyclopropyl group together with the carbon atoms to which they are attached, L is -CO-, and group A is morpholin-4-yl, then R 1 Not 5-R 11 -pyrimidin-2-yl or acetyl. Therefore, if B is a pyrrolidinyl ring, if D is a pyridyl ring, if R 2A and R 2B are linked to each other (together with the carbon atoms to which they are attached) to form a cyclopropyl group, if L is -CO-, and if group A is morpholin-4-yl, then preferably, group R 1 Not 5-R 11 -pyrimidin-2-yl or acetyl (ie preferably, R 1 The 5-position of the pyrimidine ring does not have a substituent R 11 pyrimidin-2-yl, and R 1 More preferably, if ring B is a pyrrolidinyl ring, ring D is a pyridyl ring, L is -CO-, and group A is morpholin-4-yl, then R 1 Not 5-R 11 Even more preferably, if ring B is a pyrrolidinyl ring, ring D is a pyridyl ring, and L is -CO-, then R 1 Not 5-R 11Even more preferably, if ring B is a pyrrolidinyl ring and L is -CO-, then R 1 Not 5-R 11 -pyrimidin-2-yl or acetyl. Even more preferably, if ring B is a pyrrolidinyl ring, R 1 Not 5-R 11 -pyrimidin-2-yl or acetyl. Still even more preferably, R 1 Not 5-R 11 -pyrimidin-2-yl (ie R 1 is different from 5-R 11 -pyrimidin-2-yl group) and / or R 1 is not acetyl. Still more preferably, R 1 Not 5-R 11 -pyrimidin-2-yl and is not acetyl.

[0185] Furthermore, as mentioned above, preferably, the following conditions apply to the compounds of formula (I): if ring B and ring D together constitute 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 Each is methyl, R 1 is optionally replaced by one or more groups R 11 Substituted phenyl, L is -CO-, and group A is -NH-R N , then R N is not a heterocycloalkyl group containing one oxidized sulfur ring atom, wherein all other ring atoms are carbon atoms, and said heterocycloalkyl group is substituted with methyl. Thus, if 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, if R 2A and R 2B Each is a methyl group, if R 1 is optionally replaced by one or more groups R 11 Substituted phenyl, if L is -CO-, if group A is -N(-R N )-R N , and if a group R N is hydrogen, then preferably, another group R Nis not a heterocycloalkyl group, the heterocycloalkyl group contains one oxidized sulfur ring atom (in particular the ring atom -S(=O)2-), wherein all other ring atoms are carbon atoms, and the heterocycloalkyl group is substituted by methyl. More preferably, if 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 group A is -NH-R N , then R N is not a heterocycloalkyl group containing one oxidized sulfur ring atom, wherein all other ring atoms are carbon atoms and said heterocycloalkyl group is substituted with methyl. Even more preferably, if 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 group A is -NH-R N , then R N is not a heterocycloalkyl group containing one oxidized sulfur ring atom, wherein all other ring atoms are carbon atoms and said heterocycloalkyl group is substituted with methyl. Even more preferably, if ring B is a 2-oxopyrrolidinyl ring, ring D is a pyridyl ring or a pyridazinyl ring, L is -CO-, and group A is -NH-R N , then R N is not a heterocycloalkyl group containing one oxidized sulfur ring atom, wherein all other ring atoms are carbon atoms and are substituted by methyl groups. Even more preferably, if ring B is a 2-oxopyrrolidinyl ring and group A is -NH-R N , then R N is not a heterocycloalkyl group containing one sulfur oxide ring atom, wherein all other ring atoms are carbon atoms and said heterocycloalkyl group is substituted by methyl. Still even more preferably, group A is not -NH-R N , where R N is a heterocycloalkyl group containing one sulfur oxide ring atom, wherein all other ring atoms are carbon atoms, and said heterocycloalkyl group is substituted with methyl. Still more preferably, group A is not -NH-R N , where R N is optionally replaced by one or more groups R Cyc Substituted heterocycloalkyl.

[0186] Furthermore, as mentioned above, preferably, the following conditions apply to the compounds of formula (I): if ring B and ring D together form 3-R X-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring, R X is -OH, R 2A and R 2B One of them is a methyl group, R 2A and R 2B The other one is -CON(-CH3)2, R 1 is methyl, L is -CO-, and group A is -NH-R N , then R N Therefore, if ring B and ring D together form a 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring, which is replaced by a group R at the 3-position X Substituted, the group R X is -OH, if R 2A and R 2B If one of the R 2A and R 2B The other one is -CON(-CH3)CH3, if R 1 is methyl, if L is -CO-, and if group A is -NH-R N , then preferably, R N Not 4-fluorobenzyl (ie R N More preferably, if ring B and ring D together form 3-R X -4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring, and if L is -CO-, then R X Even more preferably, if ring D is optionally substituted by one or more groups R X substituted pyrazolyl ring, and if L is -CO-, then the one or more groups R X Not -OH.

[0187] As also mentioned above, preferably, the following conditions apply to the compounds of formula (I): if 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-, group A is -NH-R N , and R 1 is -CH2-phenyl or -CH2-pyridyl, wherein the phenyl group in the -CH2-phenyl group and the pyridyl group in the -CH2-pyridyl group are each optionally substituted by one or more groups R 11 Substitution, then R 2A and R 2BMore preferably, if 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 group A is -NH-R N , then R 2A and R 2B Even more preferably, if 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, a 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine ring or a 2-R Y -2,3-dihydro-1H-pyrrolo[2,3-b]pyridine ring, L is -CO-, and group A is -NH-R N , then R 2A and R 2B is not methyl. Still even more preferably, if ring B is a 2-oxopyrrolidinyl ring or a 2-R Y -pyrrolidinyl ring, ring D is a pyridyl ring, L is -CO-, and group A is -NH-R N , then R 2A and R 2B Not meth.

[0188] In addition to the above, preferably, formula (I) does not include the compound 1-(tert-butyl)-6-((4-fluorophenyl)carbamoyl)-2-oxo-1,2-dihydrospiro[pyrido[2,3-b][1,4]oxazine-3,3'-pyrrolidine]. More preferably, if ring B is a ring containing a ring carrying R 2A and R 2B A non-aromatic 4- to 8-membered heterocyclic ring having adjacent -C(=O)- ring atoms, wherein the ring B is optionally substituted by one or more groups R Y Replace, and if R 2A and R 2B are linked to each other so as to form, together with the carbon atoms to which they are attached, a group optionally substituted by one or more groups R 21 Substituted pyrrolidin-3-yl, then R 1 Even more preferably, if ring B is a ring containing a ring carrying R 2A and R 2B A non-aromatic 4- to 8-membered heterocyclic ring having adjacent -C(=O)- ring atoms, wherein the ring B is optionally substituted by one or more groups R Y Replace, and if R 2A and R 2Bare linked to each other so as to form, together with the carbon atoms to which they are attached, a group optionally substituted by one or more groups R 21 substituted heterocycloalkyl, then the heterocycloalkyl is not pyrrolidin-3-yl.

[0189] Particularly preferably, the compound of formula (I) is any one of the specific compounds of formula (I) described in the Examples section of this specification, including any one of Examples 1-282 further described below, which is in non-salt form and / or non-solvate form, or as a pharmaceutically acceptable salt or solvate of the corresponding compound.

[0190] Therefore, it is particularly preferred that the compound of formula (I) is selected from:

[0191] 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]pyridin]-2′(1′H)-one;

[0192] 1′-(4-chloro-3-fluorophenyl)-5′-(2,2-dimethyl-3-oxopiperazine-1-carbonyl)spiro[cyclopentane-1,3′-pyrrolo[3,2-b]pyridin]-2′(1′H)-one;

[0193] 4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-2-one;

[0194] 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;

[0195] 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 ester;

[0196] 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;

[0197] 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;

[0198] 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;

[0199] 4-(1'-(3-chlorophenyl)-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-2-one;

[0200] 4-(1'-(2-chlorophenyl)-1',2'-dihydrospiro[cyclopentane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-2-one;

[0201] 4-(3,3-dimethyl-1-(thien-3-yl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one;

[0202] 4-(1-(3,4-difluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one;

[0203] 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;

[0204] 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;

[0205] 4-(1-(4-Fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)-3,3-dimethylpiperazin-2-one;

[0206] 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;

[0207] 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;

[0208] 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;

[0209] 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;

[0210] (1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-5-yl)(3,3-dimethylmorpholino)methanone;

[0211] 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;

[0212] (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;

[0213] (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;

[0214] 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;

[0215] 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;

[0216] 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;

[0217] 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;

[0218] 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;

[0219] 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;

[0220] 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;

[0221] 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;

[0222] 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;

[0223] 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;

[0224] 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-carboxylic acid ethyl ester;

[0225] 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-carboxylic acid;

[0226] 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;

[0227] 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;

[0228] 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;

[0229] 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;

[0230] 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;

[0231] 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;

[0232] 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 ester;

[0233] 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;

[0234] 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 ester;

[0235] 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;

[0236] 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;

[0237] 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;

[0238] 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;

[0239] 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;

[0240] 3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)butanoic acid;

[0241] 3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)butanoic acid methyl ester;

[0242] (R)-3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)butanoic acid methyl ester;

[0243] (R)-3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)butanoic acid;

[0244] N-(1-Carbamoylcyclopropyl)-1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide;

[0245] methyl 6-((2-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)ethyl)(methyl)amino)-2,4-dimethylnicotinate;

[0246] 6-((2-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)ethyl)(methyl)amino)-2,4-dimethylnicotinic acid;

[0247] 1-(4-chloro-3-fluorophenyl)-N-(1-hydroxy-2-methylprop-2-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide;

[0248] 1-(4-chloro-3-fluorophenyl)-N-(2-hydroxy-2-methylpropyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide;

[0249] 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;

[0250] N-(1-carbamoylcyclopropyl)-1-(4-chloro-3-fluorophenyl)-3-ethyl-3-methyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamide;

[0251] 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;

[0252] 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;

[0253] 4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclopropane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-2-one;

[0254] 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;

[0255] 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;

[0256] 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;

[0257] 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;

[0258] 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;

[0259] 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;

[0260] 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;

[0261] 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;

[0262] 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;

[0263] 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-carboxylic acid ethyl ester;

[0264] (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;

[0265] 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 ester;

[0266] 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;

[0267] 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;

[0268] 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;

[0269] 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 methyl ester;

[0270] 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;

[0271] 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;

[0272] 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;

[0273] 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;

[0274] 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;

[0275] 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 ethyl ester;

[0276] 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;

[0277] 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;

[0278] (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;

[0279] (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;

[0280] 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;

[0281] 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;

[0282] 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;

[0283] 6-(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;

[0284] 6-(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;

[0285] 6-(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;

[0286] 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;

[0287] 6-(4-(1'-(4-chloro-3-fluorophenyl)-3-fluoro-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-2-ene-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid;

[0288] 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;

[0289] 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;

[0290] 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;

[0291] 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;

[0292] (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 ethyl ester;

[0293] (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;

[0294] 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;

[0295] 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;

[0296] 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;

[0297] 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;

[0298] (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;

[0299] 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;

[0300] 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;

[0301] 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;

[0302] 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;

[0303] 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;

[0304] 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;

[0305] 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;

[0306] 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;

[0307] 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;

[0308] 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 hydrochloride;

[0309] 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;

[0310] 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;

[0311] 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;

[0312] 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;

[0313] 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;

[0314] 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;

[0315] 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;

[0316] 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;

[0317] 1′-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)spiro[indoline-3,3′-pyrrolidino]-2-one;

[0318] 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;

[0319] 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]hept-2-yl)nicotinate;

[0320] 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]hept-2-yl)nicotinic acid;

[0321] 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;

[0322] 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;

[0323] 4-(1'-(4-chloro-3-fluorophenyl)-1',2'-dihydrospiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carbonyl)-3,3-dimethylpiperazin-2-one;

[0324] 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;

[0325] 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;

[0326] 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;

[0327] 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;

[0328] 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]pyridin-1-yl)nicotinoyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate;

[0329] 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;

[0330] 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]pyridin-1-yl)nicotinoyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid;

[0331] 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;

[0332] 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;

[0333] 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 ethyl ester;

[0334] (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;

[0335] (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;

[0336] 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;

[0337] 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;

[0338] 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 ester;

[0339] 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;

[0340] 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;

[0341] 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;

[0342] 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;

[0343] 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;

[0344] 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;

[0345] 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;

[0346] 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;

[0347] 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;

[0348] 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;

[0349] 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;

[0350] 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;

[0351] 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;

[0352] 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;

[0353] 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;

[0354] 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;

[0355] 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;

[0356] 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;

[0357] 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;

[0358] 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;

[0359] 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;

[0360] 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;

[0361] 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;

[0362] 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;

[0363] 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;

[0364] 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;

[0365] 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;

[0366] 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;

[0367] 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;

[0368] 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;

[0369] 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;

[0370] 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;

[0371] 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;

[0372] 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;

[0373] 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;

[0374] 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;

[0375] 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;

[0376] 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;

[0377] 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;

[0378] 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;

[0379] 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;

[0380] 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;

[0381] 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;

[0382] 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;

[0383] 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;

[0384] 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;

[0385] 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;

[0386] 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;

[0387] 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;

[0388] 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;

[0389] 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;

[0390] 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;

[0391] 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;

[0392] 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;

[0393] 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;

[0394] 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;

[0395] 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;

[0396] 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;

[0397] 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;

[0398] 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;

[0399] 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;

[0400] 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;

[0401] 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;

[0402] 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;

[0403] 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;

[0404] 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;

[0405] 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;

[0406] 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;

[0407] 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;

[0408] 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;

[0409] 6-(4-((1s,3s)-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;

[0410] 6-(4-((1s,3s)-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;

[0411] 6-(4-((1r,3r)-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;

[0412] 6-(4-((1r,3r)-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;

[0413] 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;

[0414] 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;

[0415] 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;

[0416] 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;

[0417] 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;

[0418] 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;

[0419] 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;

[0420] 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;

[0421] 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;

[0422] 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;

[0423] 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;

[0424] 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;

[0425] 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;

[0426] 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;

[0427] 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;

[0428] 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;

[0429] 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;

[0430] 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;

[0431] 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;

[0432] 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;

[0433] 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;

[0434] 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;

[0435] 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;

[0436] 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;

[0437] 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;

[0438] 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;

[0439] 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;

[0440] 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;

[0441] 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;

[0442] 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;

[0443] 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;

[0444] 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;

[0445] 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;

[0446] 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;

[0447] 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;

[0448] 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;

[0449] 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;

[0450] 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;

[0451] 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;

[0452] 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;

[0453] 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;

[0454] 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;

[0455] 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;

[0456] 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;

[0457] 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;

[0458] 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;

[0459] 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;

[0460] 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;

[0461] 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;

[0462] 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;

[0463] 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;

[0464] 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;

[0465] 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;

[0466] 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;

[0467] 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;

[0468] 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;

[0469] 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;

[0470] 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;

[0471] 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;

[0472] 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;

[0473] 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;

[0474] 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;

[0475] 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;

[0476] 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;

[0477] 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;

[0478] 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 methyl ester;

[0479] 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;

[0480] 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-triazaheptatriacontyl)-N-methylpalmitamide;

[0481] 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;

[0482] 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;

[0483] 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;

[0484] 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;

[0485] 1-(1-((5'-(4-chloro-3-fluorophenyl)-3,3-dimethyl-5',6'-dihydrospiro[cyclobutane-1,7'-pyrrolo[2,3-b]pyrazin]-2'-yl)sulfonyl)piperidin-4-yl)imidazolidin-2-one;

[0486] 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;

[0487] 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;

[0488] 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;

[0489] 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;

[0490] 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;

[0491] 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;

[0492] 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;

[0493] 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;

[0494] 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;

[0495] 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;

[0496] 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;

[0497] 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;

[0498] 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;

[0499] 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;

[0500] 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;

[0501] 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;

[0502] or a pharmaceutically acceptable salt or solvate of any one of the above compounds.

[0503] The present invention also relates to each of the intermediates further described in the Examples section of the specification below, including any of these intermediates in non-salt form and / or non-solvate form, or in salt or solvate form (e.g., pharmaceutically acceptable salts or solvates) of the corresponding compounds. Such intermediates can be used, in particular, to synthesize compounds of formula (I).

[0504] For those skilled in the art of synthetic chemistry, it is apparent that various methods for preparing compounds of general formula (I) and pharmaceutically acceptable salts and solvates thereof. For example, 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, compounds of formula (I) can be synthesized according to the method described in the following general scheme (general disconnection method).

[0505] Schematic overview:

[0506]

[0507] According to the general cleavage method A, the compound of formula (I) can be obtained from the precursor (II)-A:

[0508]

[0509] Z N is a hydrogen atom:

[0510] - by N-derivatization methods known to those skilled in the art using an appropriate partner (based on the work 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).

[0511] - by synthesizing aniline from appropriate aldehyde or ketone derivatives (based on work described in Org. Lett., 2012, 14, 5606-5609 or Nature, 2020, 584, 75-81).

[0512] Z N It is a methyl group:

[0513] - N-arylation by using appropriate aryl alkyne precursors (based on work described in Org. Lett., 2013, 15, 5452-5455).

[0514] Z N is a benzoic acid group:

[0515] - Metal-catalyzed debenzoylation N-arylation by using appropriate organometallic partners (based on work described in J. Org. Chem., 2006, 71, 219-224).

[0516] Z N is a substituted carbonyl group:

[0517] - by rearrangement of the corresponding amide derivatives (based on the work described in Synlett 2013, 24, 1448-1454), or by rearrangement of the corresponding carbamate derivatives (based on the work described in J. Am. Chem. Soc., 2019, 141, 7262-7265).

[0518] - Metal-catalyzed deacylation of N-arylation using appropriate halogenated or pseudohalogenated aryls (based on Org.

[0519] Lett. 2021, 23, 3, 687–691 or work described in J. Org. Chem., 2012, 77, 9236-9239).

[0520] According to the general cleavage method B1, the compound of formula (I) can be obtained from the precursor (II)-B1:

[0521]

[0522] Z L is a hydrogen atom (based on work described in ARKIVOC 2013, 1, 154-174, ARKIVOC 2001, 1, 242-268 or Synthesis 2011, 20, 3209-3219):

[0523] - by N-oxidation followed by a sequence to give the carboxylic, sulfonic or sulfinic acid and subsequent synthesis of the amide, sulfonamide or sulfinamide with the appropriate amine.

[0524] - by N-oxidation, followed by Z L Sequential conversion to halogen or pseudohalogen procedures followed by the conversion or procedures described below.

[0525] - C-H bond activation using metals leads to Z LConversion to a halogen, pseudohalogen, or organometallic group is followed by the transformations or procedures described below.

[0526] Z L is a hydroxyl group (based on the work described in Org. Process Res. Dev. 2004, 8, 62-71 or Tet. Lett., 1992, 33, 1181-1184):

[0527] - By the method known to those skilled in the art, Z L The conversion or procedure to a halogen or pseudohalogen is followed by the conversion or procedure described below.

[0528] Z L is a halogen or pseudohalogen, or an organometallic group:

[0529] - Synthesis of sulfenamides or sulfonamides via direct metal-catalyzed aminocarbonylation with appropriate amines (based on the work described in RSC Adv., 2014, 4, 10367-10389 or Synthesis, 2008, 311-312).

[0530] - by transformations or procedures known to those skilled in the art to give carboxylic acids, sulfonic acids or sulfinic acids, followed by synthesis of amides, sulfonamides or sulfinamides using appropriate amines (based on work described in J. Org. Chem., 2008, 73, 3967-3969).

[0531] According to the general cleavage method B2, the compound of formula (I) can be obtained from the precursor (II)-B2:

[0532]

[0533] By transformations or procedures known to those skilled in the art to give tertiary amides, sulfonamides or sulfinamides, for example by procedures involving deprotonation and N-substitution with a suitable partner, or metal-catalyzed N-derivatization.

[0534] According to the general cleavage method C1, the compound of formula (I) can be obtained from the precursor (II)-C1:

[0535]

[0536] Z A2 is a halogen or pseudohalogen and R A1 , Y1 or Y2 is connected to a carbonyl group (based on the work described in Chemistry Open, 2020, 9, 100–17 or Acc. Chem. Res. 2008, 41, 11, 1545–1554):

[0537] - Derivatization by halogen metal exchange followed by metal-catalyzed coupling using appropriate partners.

[0538] - by halogen metal exchange followed by nucleophilic displacement or nucleophilic addition on the appropriate partner

[0539] displacement or nucleophilic addition on the appropriate partner).

[0540] - Direct nucleophilic displacement of halogens or pseudohalogens by using appropriate nucleophiles.

[0541] Z A2 is a hydrogen atom and R A1 , Y1 or Y2 is connected to a carbonyl group (based on the work described in Chemistry Open, 2020, 9, 100–17 or Acc. Chem. Res. 2008, 41, 11, 1545–1554):

[0542] - Derivatization by metalation followed by metal-catalyzed coupling using appropriate partners.

[0543] - by metalation followed by nucleophilic displacement or nucleophilic addition on an appropriate partner.

[0544] - Direct nucleophilic displacement of halogens or pseudohalogens by using appropriate nucleophiles.

[0545] - by oxidative coupling (based on work described in Angew. Chem. Int. Ed. 2017, 56, 5921–5925).

[0546] Z A2 is a hydrogen atom and Y1 is a bond:

[0547] - Photoredox-catalyzed α-derivatization of amines by using appropriate free radical acceptors (based on J.Am.Chem.

[0548] Soc. 2020, 15, 142, 11972–11977 or Chem. Rev., 2013, 113, 5322–5363). A2 is a halogen or pseudohalogen and Y2 is a bond:

[0549] - Metal-catalyzed coupling by using appropriate partners (based on work described in Org. Lett., 2009, 11, 23, 5514-5517).

[0550] According to the general cutting method C 2 / 3 / 4 From the precursors (II)-C2, (II)-C3 or (II)-C4, compounds of formula (I) can be obtained:

[0551]

[0552] - [2+1] cycloaddition by using appropriate partners (based on the work described in Chem. Rev. 2017, 117, 18, 11651–11679).

[0553] - by epoxidation followed by epoxide ring opening with an appropriate partner (based on the work described in Chem. Soc. Rev., 2011, 40, 1722-1760, J. Am. Chem. Soc. 1993, 115, 19, 8867-8868, or Synlett, 2005, 8, 1199-1222).

[0554] - [2+2] cycloaddition by using an appropriate partner (based on the work described in Eur. J. Org. Chem., 2020, 10, 1310-1326, or Chem. Rev. 2016, 116, 9748-9815).

[0555] - [2+2] cycloaddition using an appropriate carbonyl group, followed by opening of the corresponding oxetane with an appropriate partner (based on the work described in Molecules, 2013, 18, 11384-11428, or Chem. Rev., 2016, 116, 12150-12233).

[0556] - [2+3] cycloaddition by using an appropriate partner (based on the work described in Beilstein J. Org. Chem. 2020, 16, 3015-3031, or Chem. Rev. 2005, 105, 2765-2809).

[0557] - [2+4] Diels-Alder cycloaddition by using an appropriate diene or using an appropriate dienophile (based on Chem.

[0558] Rev. 1942, 31, 2, 319–523, or the work described in Chem. Soc. Rev., 2018, 47, 7926).

[0559] - by using a (II)-C3 (Y2 is -CZ-) or imine (Y2 is N) containing a conjugated double bond or with a (II)-C4 (Y1 is -CZ2-C(O)-) sulfonyl (Y1 is -CZ2-S(O)2-) or imine (Y1 is a bond) containing an α,β-unsaturated carbonyl group by nucleophilic addition known to those skilled in the art.

[0560] - by electrophilic addition at the exocyclic double bond on (II)-C4 (Y1 is -CZ-) known to those skilled in the art.

[0561] In addition, using a synthesis strategy based on dearomatization of each aromatic compound, specific intermediates (II)-C2, (II)-C3 and (II)-C4 can be obtained, or they can be used as precursors to obtain compounds of formula (I) (based on 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 work described in Tetrahedron, 2019, 75, 2063–2097).

[0562] According to the general cutting method D 1 / 2 / 3 / 6 From the precursors (II)-D1 (II)-D2, (II)-D3, or (II)-D6, compounds of formula (I) can be obtained:

[0563]

[0564] Z1 is hydrogen or an organometallic group, or a halogen or a pseudohalogen, and Z2, Z Y1 , Z Y2 , Z Y3 are respectively a halogen or pseudohalogen, or hydrogen or an organometallic group:

[0565] - by metal-catalyzed coupling reactions known to those skilled in the art.

[0566] Z1 is hydrogen, halogen or pseudohalogen, and Z2, Z Y1 , Z Y2 , Z Y3 are halogen or pseudohalogen, or hydrogen, respectively:

[0567] - by directed metalation followed by intramolecular nucleophilic substitution or nucleophilic aromatic substitution known to those skilled in the art.

[0568] - by nucleophilic substitution or nucleophilic aromatic substitution known to those skilled in the art.

[0569] Z1 and Z2, Z Y1 , Z Y2 , Z Y3 All are halogens or pseudohalogens:

[0570] By metal-catalyzed reductive coupling (based on the work described in Chem. Eur. J. 2014, 20, 15334-15338, or Chem. Eur. J. 2014, 20, 6828-6842).

[0571] Z1 and Z2, Z Y1 , Z Y2 , Z Y3 Is a suitable pairing:

[0572] -Through the universal cutting method C 2 / 3 / 4 Suitable cycloaddition reactions are mentioned in .

[0573] According to the general cutting method D 4 / 5 From the precursor (II)-D4 or (II)-D5, the compound of formula (I) can be obtained:

[0574]

[0575] Z N is a carbonyl group:

[0576] - by reductive amination or amide synthesis known to those skilled in the art.

[0577] - by Petasis reaction (based on Chem. Rev. 2019, 119, 11245–11290 or RSC Adv., 2015, 5,

[0578] 76337–76341).

[0579] Z N is a halogen or pseudohalogen, or an organometallic group:

[0580] - by nucleophilic substitution known to those skilled in the art.

[0581] - by metal-catalyzed coupling reaction (based on the work described in Chem. Rev. 2016, 116, 19, 12564–12649, Chem. Soc. Rev., 2014, 43, 3525–3550, or Chem. Rev. 2019, 119, 24, 12491–12523).

[0582] According to the general cleavage method E1, the compound of formula (I) can be obtained from the precursor (II)-E1:

[0583]

[0584] - by cross-coupling reactions, reductive coupling or cross-metathesis known to those skilled in the art.

[0585] - by Petasis or Mannich reaction (based on the work 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).

[0586] According to the general cleavage method E2, the compound of formula (I) can be obtained from the precursor (II)-E2:

[0587]

[0588] - By using R N -NH2 double reductive amination.

[0589] - By using R N -NH2 undergoes dinucleophilic (aromatic) substitution.

[0590] - By using R N -NH2 undergoes one-pot reductive amination and nucleophilic substitution.

[0591] According to the general cutting method E 3 / 4 From the precursors (II)-E3 and / or (II)-E4, compounds of formula (I) can be obtained:

[0592]

[0593] -by heterocyclic synthesis from precursor (II)-E3 known to those skilled in the art, more specifically, by Topics in Current Chemistry, 2019, 377, 21, Synthetic Communications, 2020, 50, 1251–1285, Org.

[0594] The specific methods described in Chem. Front., 2019, 6, 2120-2141, Chem. Rev. 2011, 111, 4, 2937–2980, or Synlett, 2011, 2387-2391.

[0595] -Synthesized by cycloaddition reactions to give heteroaromatic rings known to those skilled in the art, more specifically, based on the method of Org.

[0596] Chem.Front.,2014,1,1010-1015, J.Am.Chem.Soc.1999,121,54-62, Acc.Chem.Res.

[0597] 2020, 53, 4, 773–781 or the procedures of the work described in CRChimie, 2017, 20, 643–647.

[0598] - Synthesis by cycloaddition reactions known to those skilled in the art to give non-aromatic heterocycles, more specifically, heteroaryne conversions based on the work described in Angew. Chem. Int. Ed., 2015, 54, 11765-11769, or Chem. Rev. 2021, 121, 3892-4044.

[0599] Use and combine the above general cutting methods A, B1, B2, C1, C 2 / 3 / 4 、D 1 / 2 / 3 / 6 、D 4 / 5 、E1、E2、E 3 / 4 , and available literature, any compound of formula (I) can be synthesized from commercially available compounds and / or from compounds whose synthesis has been described in the literature or compounds obtainable by methods known in the art.

[0600] Unless expressly stated otherwise, the following definitions apply throughout this specification and claims.

[0601] The term "hydrocarbyl" refers to a group consisting of carbon and hydrogen atoms.

[0602] The term "alicyclic" is used in conjunction with a cyclic group to indicate that the corresponding cyclic group is non-aromatic.

[0603] As used herein, the term "alkyl" refers to a monovalent, saturated, acyclic (i.e., non-cyclic) hydrocarbon group that may be straight-chain or branched. Thus, an "alkyl" group does not contain any carbon-carbon double bonds or any carbon-carbon triple bonds. 1-5"Alkyl" means an alkyl group having 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 a C 1-4 The alkyl group more preferably refers to a methyl group or an ethyl group, and even more preferably refers to a methyl group.

[0604] 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. 2-5 "Alkenyl" refers to an alkenyl group having 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., isoprene). Unless otherwise defined, the term "alkenyl" preferably refers to a C 2-4 Alkenyl.

[0605] As used herein, the term "alkynyl" 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 triple bonds and optionally contains one or more (e.g., one or two) carbon-carbon double bonds. 2-5 "Alkynyl" refers to an alkynyl group having 2 to 5 carbon atoms. Preferred exemplary alkynyl groups are ethynyl, propynyl (eg, propargyl), or butynyl. Unless otherwise defined, the term "alkynyl" preferably refers to a C 2-4 Alkynyl.

[0606] As used herein, the term "alkylene" refers to an alkanediyl group, i.e., a divalent saturated acyclic hydrocarbon group, which may be straight-chain or branched. 1-5 "Alkylene" means an alkylene group having 1 to 5 carbon atoms. 0-3 "Alkylene" indicates a covalent bond (corresponding to option "C0 alkylene") or the presence of C 1-3 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 a C 1-4 Alkylene (especially including straight chain C 1-4alkylene), more preferably refers to methylene or ethylene, even more preferably refers to methylene.

[0607] As used herein, the term "alkenylene" refers to an alkenediyl group, i.e., a divalent unsaturated acyclic hydrocarbon group, which 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. 2-5 "Alkenylene" refers to an alkenylene group having 2 to 5 carbon atoms. Unless otherwise defined, the term "alkenylene" preferably refers to a C 2-4 Alkenylene (especially including straight chain C 2-4 alkenylene).

[0608] As used herein, the term "alkynylene" refers to an alkynediyl group, i.e., a divalent unsaturated acyclic hydrocarbon group, which may be linear or branched and contains one or more (e.g., one or two) carbon-carbon triple bonds and optionally contains one or more (e.g., one or two) carbon-carbon double bonds. 2-5 "Alkyne" refers to an alkynyl group having 2 to 5 carbon atoms. Unless otherwise defined, the term "alkynyl" preferably refers to a C 2-4 Alkynylidene (especially including straight chain C 2-4 alkynylene).

[0609] As used herein, the term "carbocyclyl" (or "carbocycle") refers to a hydrocarbon ring group, including monocyclic and bridged, spirocyclic and / or fused ring systems (which may, for example, be composed of two or three rings), wherein the cyclic group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. Unless otherwise defined, "carbocyclyl" preferably refers to aryl, cycloalkyl or cycloalkenyl.

[0610] As used herein, the term "heterocyclyl" (or "heterocycle") refers to cyclic groups, including monocyclic as well as bridged, spiro and / or fused ring systems (which may be composed of, for example, two or three rings), wherein the cyclic group contains one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be optionally oxidized, wherein one or more carbon ring atoms may be optionally oxidized (i.e., to form an oxo group), and further wherein the cyclic group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. For example, each heteroatom-containing ring included in the cyclic group may contain one or two O atoms and / or one or two S atoms (which may be optionally oxidized) and / or one, two, three or four N atoms (which may be optionally oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and at least one carbon ring atom (which may be optionally oxidized) is present in the corresponding heteroatom-containing ring. Unless otherwise defined, "heterocyclyl" preferably refers to heteroaryl, heterocycloalkyl or heterocycloalkenyl.

[0611] As used herein, the term "aryl" refers to an aromatic hydrocarbon ring group, including monocyclic aromatic rings and bridged and / or fused ring systems containing at least one aromatic ring (e.g., a ring system composed of two or three fused rings, wherein at least one of the fused rings is aromatic; or a bridged ring system composed of two or three rings, wherein at least one of the bridged rings is aromatic). If the aryl group is a bridged and / or fused ring system that contains at least one non-aromatic ring (e.g., a saturated ring or an unsaturated alicyclic ring) in addition to one or more aromatic rings, one or more carbon ring atoms in each non-aromatic ring may be optionally oxidized (i.e., to form an oxo group). "Aryl" can be, 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, most preferably refers to phenyl.

[0612] As used herein, the term "heteroaryl" (or "heteroaromatic ring") refers to an aromatic ring group, including monocyclic aromatic rings and bridged and / or fused ring systems, containing at least one aromatic ring (e.g., a ring system composed of two or three fused rings, wherein at least one of the fused rings is aromatic; or a bridged ring system composed of two or three rings, wherein at least one of the bridged rings is aromatic), wherein the aromatic ring group contains one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) can be optionally oxidized, and further wherein one or more carbon ring atoms can be optionally oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring contained in the aromatic cyclic group may contain one or two O atoms and / or one or two S atoms (which may be optionally oxidized) and / or one, two, three or four N atoms (which may be optionally oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that at least one carbon ring atom (which may be optionally oxidized) is present in the corresponding heteroatom-containing ring."Heteroaryl" can be, for example, thienyl (i.e., thienyl), 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., pyridyl; e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl), pyrazinyl, pyrimidinyl, pyridazinyl, indolyl (e.g., 1H-indolyl), isoindolyl, indole, pyrimidinyl, pyridaz ... oxazolyl, 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), oxazolyl 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]thienyl (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-dihydrofuropyridinyl or 1,3-dihydrofuropyridinyl), 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 5-14 membered (more preferably a 5-10 membered) monocyclic or fused ring system comprising one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; even more preferably, "heteroaryl" refers to a 5- or 6-membered monocyclic ring comprising one or more (e.g., one, two or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized. Furthermore, unless otherwise defined, particularly preferred examples of “heteroaryl” include pyridyl (e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl), imidazolyl, thiazolyl, 1H-tetrazolyl, 2H-tetrazolyl, thienyl (i.e., thienyl), or pyrimidinyl.

[0613] As used herein, the term "cycloalkyl" refers to a saturated hydrocarbon ring group, including a monocyclic ring as well as a bridged ring, a spirocyclic ring and / or a fused ring system (which may be composed of, for example, two or three rings; for example, a fused ring system composed of two or three fused rings). "Cycloalkyl" may be, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, decahydronaphthyl (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. Furthermore, unless otherwise defined, particularly preferred examples of "cycloalkyl" include cyclohexyl or cyclopropyl, particularly cyclohexyl.

[0614] As used herein, the term "heterocycloalkyl" refers to a saturated cyclic group, including monocyclic and bridged, spirocyclic and / or fused ring systems (which can be composed of, for example, two or three rings; for example, a fused ring system composed of two or three fused rings), wherein the cyclic group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S, and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) can be optionally oxidized, and further wherein one or more carbon ring atoms can be optionally oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring contained in the saturated cyclic group can contain one or two O atoms and / or one or two S atoms (which can be optionally oxidized) and / or one, two, three, or four N atoms (which can be optionally oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4, and at least one carbon ring atom (which can be optionally oxidized) is present in the corresponding heteroatom-containing ring. "Heterocycloalkyl" may refer to, for example, aziridine, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, piperazinonyl (e.g., piperazin-2-on-1-yl or piperazin-3-on-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), -yl), oxazepanyl, oxirane, oxetanyl, tetrahydrofuranyl, 1,3-dioxolanyl, tetrahydropyranyl, 1,4-dioxanyl, oxetanyl, thiirane, thietanyl, tetrahydrothiophenyl (i.e., thiolanyl), 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 3-11 membered saturated cyclic group which is a monocyclic or fused ring system (e.g., a fused ring system consisting of two fused rings), wherein the cyclic group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S, and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; more preferably, "heterocycloalkyl" refers to a 5- to 7-membered saturated monocyclic group containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S, and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized.Furthermore, unless otherwise defined, particularly preferred examples of the "heterocycloalkyl group" include a tetrahydropyranyl group, a piperidinyl group, a piperazinyl group, a piperazinonyl group, a morpholinyl group, a pyrrolidinyl group or a tetrahydrofuranyl group.

[0615] 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 spirocyclic and / or fused ring system (which can be composed of, for example, two or three rings; for example, a fused ring system composed of two or three fused rings), wherein the hydrocarbon ring group contains one or more (e.g., one or two) carbon-carbon double bonds and does not contain any carbon-carbon triple bonds. "Cycloalkenyl" can be, for example, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl or cycloheptadienyl. Unless otherwise defined, "cycloalkenyl" preferably refers to C 3-11 Cycloalkenyl, more preferably C 3-7 Cycloalkenyl. A particularly preferred "cycloalkenyl" group is a monocyclic unsaturated alicyclic hydrocarbon ring having 3 to 7 ring members and containing one or more (eg, one or two; preferably one) carbon-carbon double bonds.

[0616] As used herein, the term "heterocyclenyl" refers to an unsaturated alicyclic (non-aromatic) ring group, including monocyclic as well as bridged, spiro and / or fused ring systems (which may be composed of, for example, two or three rings; for example, a fused ring system composed of two or three fused rings), wherein the ring group contains one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be optionally oxidized, wherein one or more carbon ring atoms may be optionally oxidized (i.e., to form an oxo group), and further wherein the 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 the unsaturated alicyclic ring group may contain one or two O atoms and / or one or two S atoms (which may be optionally oxidized) and / or one, two, three or four N atoms (which may be optionally oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that at least one carbon ring atom (which may be optionally oxidized) is present in the corresponding heteroatom-containing ring. "Heterocycloalkenyl" can be, for example, an imidazolinyl group (e.g., 2-imidazolinyl (i.e., 4,5-dihydro-1H-imidazolyl), 3-imidazolinyl, or 4-imidazolinyl), a tetrahydropyridinyl group (e.g., 1,2,3,6-tetrahydropyridinyl), a dihydropyridinyl group (e.g., 1,2-dihydropyridinyl, or 2,3-dihydropyridinyl), a pyranyl group (e.g., 2H-pyranyl, or 4H-pyranyl), a thiopyranyl group (e.g., 2H-thiopyranyl, or 4H-thiopyranyl), a dihydropyranyl group, a dihydrofuranyl group, a dihydropyrazolyl group, a dihydropyrazinyl group, a dihydroisoindolyl group, an octahydroquinolinyl group (e.g., 1,2,3,4,4a,5,6,7-octahydroquinolinyl), or an octahydroisoquinolinyl group (e.g., 1,2,3,4,5,6,7,8-octahydroisoquinolinyl).Unless otherwise defined, "heterocycloalkenyl" preferably refers to a 3-11 membered unsaturated alicyclic ring group which is a monocyclic or fused ring system (e.g. a fused ring system consisting of two fused rings), wherein the ring group contains one or more (e.g. one, two, three or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be optionally oxidized, wherein one or more carbon ring atoms may be optionally oxidized, and wherein the ring group contains at least one between adjacent ring atoms. double bond, 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., one, two or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may be optionally oxidized, wherein one or more carbon ring atoms may be optionally oxidized, and wherein the ring group contains at least one double bond between adjacent ring atoms, and does not contain any triple bonds between adjacent ring atoms.

[0617] As used herein, the term "halogen" refers to fluorine (-F), chlorine (-Cl), bromine (-Br), or iodine (-I).

[0618] As used herein, the term "haloalkyl" refers to an alkyl group substituted with one or more (preferably 1 to 6, more preferably 1 to 3) halogen atoms independently selected from fluorine, chlorine, bromine and iodine, preferably all fluorine atoms. It will be understood that the maximum number of halogen atoms is limited by the number of available attachment positions and therefore depends on the number of carbon atoms contained in the alkyl portion of the haloalkyl group. "Haloalkyl" can be, for example, -CF3, -CHF2, -CH2F, -CF2-CH3, -CH2-CF3, -CH2-CHF2, -CH2-CF2-CH3, -CH2-CF2-CF3 or -CH(CF3)2. Particularly preferred "haloalkyl" is -CF3.

[0619] The terms "valent bond" and "covalent bond" are used synonymously herein unless explicitly stated otherwise or contradicted by context.

[0620] As used herein, the terms "optional," "optionally," and "may" indicate that a given feature may be present but may not be present. Whenever "optional," "optionally," or "may" is used, the present invention specifically contemplates both possibilities, i.e., the corresponding feature is present, or the corresponding feature is not present. For example, the expression "X is optionally substituted by Y" (or "X may be substituted by Y") means that X is either substituted by Y or not substituted. Similarly, if a component of a composition is indicated as "optional," the present invention specifically contemplates both possibilities, i.e., the corresponding component is present (included in the composition) or the corresponding component is not present in the composition.

[0621] In this specification, various groups are referred to as "optionally substituted". Typically, these groups may carry one or more substituents, for example, two, three or four substituents. It will be understood that the maximum number of substituents is limited by the number of available attachment positions on the substituted part. Unless otherwise defined, groups referred to in this specification as "optionally substituted" preferably carry no more than two substituents, and in particular may carry only one substituent. Furthermore, unless otherwise defined, it is preferred that no optional substituent is present, i.e., the corresponding group is unsubstituted.

[0622] It will be appreciated by those skilled in the art that the substituents included in the compounds of the present invention can be connected to the remainder of the corresponding compound through many different positions of the corresponding specific substituents. Unless otherwise defined, the preferred connection positions of the various specific substituents are as shown in the examples.

[0623] As used herein, unless expressly stated otherwise or contradicted by context, the terms "a," "an," and "the" can be used interchangeably with "one or more" and "at least one." Thus, for example, a composition comprising "a" compound of Formula (I) can be interpreted to mean a composition comprising "one or more" compounds of Formula (I).

[0624] It should be understood that wherever a numerical range is provided / disclosed herein, all values ​​and subranges encompassed by the corresponding numerical range are intended to be encompassed within the scope of the present invention. Therefore, the present invention is specifically and individually directed to each and every value falling within the numerical range disclosed herein, and each and every subrange encompassed by the numerical range disclosed herein.

[0625] As used herein, the term "about" preferably refers to ±10% of the given numerical value, more preferably ±5% of the given numerical value, and especially the exact numerical value given. If the term "about" is used in conjunction with the endpoints of a range, it preferably refers to a range from -10% of the lower endpoint to +10% of the upper endpoint of the given numerical value, more preferably from -5% of the lower endpoint to +5% of the upper endpoint, and even more preferably refers to a range defined by the exact numerical values ​​of the lower endpoint and the upper endpoint.

[0626] As used herein, unless expressly stated otherwise or contradicted by the context, the term "comprising" (or "containing", "including", "including") has the meaning of "especially containing", that is, "containing among other optional elements...". In addition, the term also includes the narrower meanings of "essentially consisting of" and "consisting of." For example, the term "A comprising B and C" has the meaning of "A especially comprising B and C", where A may contain other optional elements (e.g., A "comprising B, C and D" would also be included), but the term also includes the meaning of "A essentially consisting of B and C" and the meaning of "A consisting of B and C" (i.e., A does not contain other components besides B and C).

[0627] 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 protonating an atom carrying a lone electron pair susceptible to protonation, such as an amino group, with an inorganic or organic acid, or salts with an acid group having a physiologically acceptable cation, such as a carboxylic acid group. 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 salts, meglumine salts, ethylenediamine salts, or choline salts; arylalkylamine salts such as N,N-dibenzylethylenediamine salts, benzathine salts, benethamine salts; heterocyclic aromatic amine salts such as pyridinium salts, picoline salts, quinolinium salts, or isoquinolinium salts; quaternary ammonium salts such as tetramethylammonium salts, tetrabutylammonium salts, benzyltrimethylammonium salts, benzyltriethylammonium salts, benzyltributylammonium salts, methyltrioctylammonium salts, or tetrabutylammonium salts; and basic amino acid salts such as arginine salts, lysine salts, or histidine salts. Exemplary acid addition salts include, for example, inorganic acid salts such as hydrochlorides, hydrobromides, hydroiodides, sulfates (e.g., sulfate or bisulfate), nitrates, phosphates (e.g., phosphate, hydrogenphosphate, or dihydrogenphosphate), carbonates, bicarbonates, perchlorates, borates, or thiocyanates; organic acid salts such as acetates, propionates, butyrates, valerates, hexanoates, heptanoates, octanoates, cyclopentanepropionates, decanoates, undecanoates, oleates, stearates, lactates, maleates, oxalates, fumarates, tartrates, malates, citrates, succinates, adipates, gluconates, glycolates, nicotinates, benzoates, salicylates, anti- Ascorbate, pamoate (enbolate), camphorate, glucoheptonate or pivalate; sulfonates such as methanesulfonate (mesylate), ethanesulfonate (esylate), 2-hydroxyethanesulfonate (hydroxyethanesulfonate), benzenesulfonate (phenylsulfonate), p-toluenesulfonate (toluenesulfonate), 2-naphthalenesulfonate (naphthalenesulfonate), 3-phenylsulfonate or camphorsulfonate; glycerophosphate; and acidic amino acid salts such as aspartate or glutamate. Additional pharmaceutically acceptable salts are described in the literature, for example in Stahl PH & Wermuth CG (eds.), "Handbook of Pharmaceutical Salts: Properties, Selection, and Use", Wiley-VCH, 2002 and references cited therein.Preferred pharmaceutically acceptable salts of the compound of formula (I) include hydrochloride, hydrobromide, methanesulfonate, sulfate, tartrate, fumarate, acetate, citrate and phosphate. A particularly preferred pharmaceutically acceptable salt of the compound of formula (I) is the hydrochloride. Thus, it is preferred that the compound of formula (I), including any of the specific compounds of formula (I) described herein, is in the form of a hydrochloride, hydrobromide, methanesulfonate, sulfate, tartrate, fumarate, acetate, citrate or phosphate, and it is particularly preferred that the compound of formula (I) is in the form of a hydrochloride.

[0628] The present invention also particularly relates to compounds of formula (I), including any of the specific compounds of formula (I) described herein, in non-salt form.

[0629] In addition, the scope of the present invention encompasses compounds of formula (I) in any solvate form, including, for example, solvates with water (i.e., hydrates) or with organic solvents, such as methanol, ethanol, isopropanol, acetic acid, ethyl acetate, ethanolamine, DMSO, or acetonitrile. All physical forms of compounds of formula (I), including any amorphous or crystalline form (i.e., polymorphs), are also included within the scope of the present invention. It should be understood that such solvates and physical forms of pharmaceutically acceptable salts of compounds of formula (I) are also included within the present invention.

[0630] In addition, 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 thiol / thiol tautomers). All such isomers of the compounds of formula (I) are considered to be part of the present invention, whether in the form of a mixture or in pure or substantially pure form. As for stereoisomers, the present invention includes the isolated optical isomers of the compounds of the present invention and any mixtures thereof (including in particular racemic mixtures / racemates). Racemates can be separated by physical methods such as fractional crystallization, separation or crystallographic resolution of diastereomeric derivatives or by chiral column chromatography. Individual optical isomers can also be obtained from the racemates by salification with an optically active acid followed by crystallization. The present invention also encompasses any tautomers of the compounds of formula (I). It should be understood that some compounds can exhibit tautomerism. In such cases, the formulas provided herein specifically depict one of the possible tautomeric forms. It is intended that the formulas and chemical names provided herein encompass any tautomeric form of the corresponding compounds, but are not limited to the specific tautomeric form depicted or identified by the compound name.

[0631] 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 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") substituted compounds of formula (I). Therefore, the present invention also covers deuterium-enriched compounds of formula (I). Naturally occurring hydrogen is a compound containing about 99.98 mol-% hydrogen-1 ( 1 H) and about 0.0156 mol-% deuterium ( 2 H or D) isotope mixture. The content of deuterium on one or more hydrogen positions in the compound of formula (I) can be increased using deuteration techniques known in the art. For example, the reactant or precursor used for the compound of formula (I) or the compound of formula (I) can be subjected to an H / D exchange reaction using, for example, heavy water (DO). In addition, suitable deuteration techniques are described in the following documents: Atzrodt J et al., Bioorg Med Chem, 20 (18), 5658-5667, 2012; William JS et al., Journal of Labelled Compounds and Radiopharmaceuticals, 53 (11-12), 635-644, 2010; Modvig A et al., J Org Chem, 79, 5861-5868, 2014. The content of deuterium can be determined using, for example, mass spectrometry or NMR spectroscopy. Unless otherwise specified, it is preferred that the compound of formula (I) is not rich in deuterium. Therefore, it is preferred that naturally occurring hydrogen atoms or 1 H hydrogen atom.

[0632] The present invention also includes the case where one or more atoms are replaced by a positron-emitting isotope of the corresponding atom, e.g. 18 F. 11 C. 13 N. 15 O. 76 Br, 77 Br, 120 I and / or 124 I substituted compounds of formula (I). Such compounds can be used as tracers, tracking agents or imaging probes in positron emission tomography (PET). The present invention thus includes: (i) wherein one or more fluorine atoms (or, for example, all fluorine atoms) are replaced by 18 F atom substituted compounds of formula (I); (ii) wherein one or more carbon atoms (or, for example, all carbon atoms) are replaced by 11 C atom substituted compounds of formula (I); (iii) wherein one or more nitrogen atoms (or, for example, all nitrogen atoms) are replaced 13(iv) wherein one or more oxygen atoms (or, for example, all oxygen atoms) are replaced by 15 O atom substituted compounds of formula (I); (v) wherein one or more bromine atoms (or, for example, all bromine atoms) are replaced by 76 (vi) compounds of formula (I) wherein one or more bromine atoms (or, for example, all bromine atoms) are replaced by 77 (vii) compounds of formula (I) wherein one or more iodine atoms (or, for example, all iodine atoms) are replaced by 120 I atom substituted; and (viii) wherein one or more iodine atoms (or, for example, all iodine atoms) are replaced 124 Compounds of formula (I) wherein no atom is substituted by a specific isotope. In general, it is preferred that no atom in the compounds of formula (I) is substituted by a specific isotope.

[0633] The compounds provided herein can be administered in the form of the compounds themselves or can be formulated into medicaments for administration. Medicaments / pharmaceutical compositions can optionally contain one or more pharmaceutically acceptable excipients, such as carriers, diluents, fillers, disintegrants, lubricants, binders, colorants, pigments, stabilizers, preservatives, antioxidants and / or dissolution promoters.

[0634] The pharmaceutical composition may comprise one or more dissolution enhancers, such as poly(ethylene glycol), including poly(ethylene glycol) having a molecular weight of about 200 to about 5,000 Da (e.g., PEG 200, PEG 300, PEG 400, or PEG 600), ethylene glycol, propylene glycol, glycerol, nonionic surfactants, tyloxapol, polysorbate 80, polyethylene glycol-15-hydroxystearate (e.g., HS15,CAS 70142-34-6), phospholipids, lecithin, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, cyclodextrin, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxyethyl-γ-cyclodextrin, hydroxypropyl-γ-cyclodextrin, dihydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, sulfobutylether-γ-cyclodextrin, glucosyl-α-cyclodextrin dextrin, 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 sulfide, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, vinyl acetate copolymer, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, or any combination thereof.

[0635] The pharmaceutical composition may further comprise one or more preservatives, in particular one or more antimicrobial 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.

[0636] The pharmaceutical composition can be prepared 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 into dosage forms for oral, parenteral, for example, 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, medicated gums, chewable tablets and effervescent tablets. Dosage forms for parenteral administration include solutions, emulsions, suspensions, dispersants and powders and granules for reconstitution. Emulsions are preferred dosage forms for parenteral administration. Dosage forms for rectal and vaginal administration include suppositories and ovulas. Dosage forms for nasal administration can be administered by inhalation or insufflation, for example, by a metered dose inhaler.Dosage forms for topical administration include creams, gels, ointments, salves, patches and transdermal delivery systems.

[0637] The compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any of the above entities, can be administered to a subject by any convenient route of administration, whether systemically / peripherally or at the desired site of action, including but not limited to one or more of the following: oral (e.g., in tablet, capsule form or in the form of an ingestible solution), topical (e.g., transdermal, intranasal, ophthalmic, buccal and sublingual), parenteral (e.g., using injection techniques or infusion techniques, including, for example, by injection, such as subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, intravenous ...

[0014] Administration may be intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, subarachnoid, or intrasternal, e.g., via a depot implant, e.g., subcutaneous or intramuscular), pulmonary (e.g., by inhalation or insufflation therapy, using, e.g., an aerosol, e.g., through the mouth or nose), gastrointestinal, intrauterine, intraocular, subcutaneous, ocular (including intravitreal or intracameral), rectal, or vaginal.

[0638] If the compound or pharmaceutical composition are administered parenterally, the example of such administration includes one or more of the following: intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, ​​intrasternal, intracardial, intracranial, intramuscular or subcutaneous administration of the compound or pharmaceutical composition, and / or by using an infusion technique. For parenteral administration, the compound is best used in the form of a sterile aqueous solution, which can contain other substances, such as, enough salt or glucose to make solution isotonic with blood. If necessary, the aqueous solution should be suitably processed with a buffer (preferably pH 3-9). Suitable parenteral preparations prepared under aseptic conditions are easily realized by standard pharmaceutical techniques well known to those skilled in the art.

[0639] The compounds or pharmaceutical compositions can also be administered orally in the form of tablets, capsules, ova, elixirs, solutions or suspensions, which formulations may contain flavorings or coloring agents for immediate-, delayed-, modified-, sustained-, pulsed- or controlled-release applications.

[0640] Tablets may contain excipients such as microcrystalline cellulose, lactose, sodium citrate, calcium carbonate, calcium hydrogen phosphate, and glycine; disintegrants such as starch (preferably corn starch, potato starch, or tapioca starch), sodium starch glycolate, croscarmellose sodium, and certain complex silicates; and granulation binders such as polyvinyl pyrrolidone, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), sucrose, gelatin, and acacia. Lubricants such as magnesium stearate, stearic acid, glyceryl behenate, and talc may also be included. Solid compositions of 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 glycols. For aqueous suspensions and / or elixirs, the active agent may be combined with various sweeteners or flavorings, coloring substances or dyes, emulsifiers and / or suspending agents, and diluents such as water, ethanol, ethylene glycol, and glycerol, and combinations thereof.

[0641] 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 through the mouth into the gastrointestinal tract, which may also be referred to as "oral-gastrointestinal" administration.

[0642] Alternatively, the compound or pharmaceutical composition can be administered in the form of a suppository or pessary, or can be applied topically in the form of a gel, hydrogel, lotion, solution, cream, ointment or dusting powder. The compounds of the invention can also be administered dermally or transdermally, for example, by using a skin patch.

[0643] The compound or pharmaceutical composition can 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, copolymers of polylactide, L-glutamic acid and γ-ethyl-L-glutamic acid, poly-(2-hydroxyethyl methacrylate), ethylene vinyl acetate, or poly-D-(-)-3-hydroxybutyric acid. Sustained release pharmaceutical compositions also include liposome-encapsulated compounds. Therefore, the present invention also relates to liposomes containing the compounds of the present invention.

[0644] The compound or pharmaceutical composition can also be administered by pulmonary, rectal or ocular routes. For ocular administration, they can be formulated into micronized suspensions in isotonic, pH-adjusted, sterile saline, or preferably into solutions in isotonic, pH-adjusted, sterile saline (optionally in combination with a preservative such as benzalkonium chloride). Alternatively, they can be formulated in an ointment such as petrolatum.

[0645] It is also envisioned that dry powder formulations of compounds of formula (I) for pulmonary administration, particularly for inhalation, may be prepared. Such dry powders may be prepared by spray drying under conditions that produce a substantially amorphous glassy or substantially crystalline biologically active powder. Thus, dry powders of the compounds of the present invention may be prepared according to an emulsification / spray drying process.

[0646] For topical application to the skin, the compound or pharmaceutical composition can be formulated into a suitable ointment containing the active compound suspended in or dissolved in, for example, a mixture of one or more of mineral oil, liquid paraffin, white petrolatum, propylene glycol, emulsifying wax, and water. Alternatively, they can be formulated into a suitable emulsion or cream suspended in or dissolved in, for example, a mixture of one or more of mineral oil, sorbitan monostearate, polyethylene glycol, liquid paraffin, polysorbate 60, cetyl esters wax, 2-octyldodecanol, benzyl alcohol, and water.

[0647] Therefore, the present invention relates to compounds or pharmaceutical compositions provided herein, wherein the corresponding compounds or pharmaceutical compositions are administered by any of the following routes: oral route; topical route, including transdermal, intranasal, ocular, buccal or sublingual route; parenteral route using injection technology or infusion technology, including subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcutaneous, intraarticular, subarachnoid, intrasternal, intraventricular, intraurethral or intracranial route; pulmonary route, including by inhalation or insufflation therapy; gastrointestinal route; intrauterine route; intraocular route; subcutaneous route; ocular route, including by intravitreal route or intracameral route; rectal route; or vaginal route. Preferred routes of administration are oral administration or parenteral administration. For each compound or pharmaceutical composition provided herein, it is particularly preferred that the corresponding compound or pharmaceutical composition is administered orally (particularly by oral intake).

[0648] Typically, the clinician will determine the actual dosage that will be most suitable for an individual. The specific dosage level and frequency of administration for any particular individual can vary and depend on a variety of factors, including the activity of the specific compound employed, the metabolic stability and duration of action of the compound, age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, severity of the particular condition, and the individual being treated.

[0649] A suggested, but non-limiting, dosage of the compounds of the present invention for oral administration to humans (approximately 70 kg body weight) may be 0.05 mg to 2000 mg, preferably 0.1 mg to 1000 mg, of active ingredient per unit dose. A unit dose may be administered, for example, 1 to 3 times per day. For example, a unit dose may also be administered 1 to 7 times per week, with no more than one administration per day. It will be understood that it may be necessary to routinely vary the dosage depending on the age and weight of the patient / individual and the severity of the condition to be treated. The precise dosage and route of administration will ultimately be determined by the attending physician or veterinarian.

[0650] The compound of formula (I) or its pharmaceutically acceptable salt or solvate, or a pharmaceutical composition comprising any of the above entities can be administered in a monotherapy (e.g., without the concomitant administration of any additional therapeutic agent, or without the concomitant administration of any additional therapeutic agent for the same disease treated or prevented with the compound of formula (I)). However, the compound of formula (I) or its pharmaceutically acceptable salt or solvate, or a pharmaceutical composition comprising any of the above entities can also be administered in combination with one or more additional therapeutic agents. If the compound of formula (I) is used in combination with a second therapeutic agent that is active for the same disease or condition, the dose of each compound can be different from the dose when the corresponding compound is used alone, and in particular, a lower dose of each compound can be used. The combination of the compound of formula (I) and one or more additional therapeutic agents can include the simultaneous / concomitant administration of the compound of formula (I) and one or more additional therapeutic agents (in a single pharmaceutical formulation or in separate pharmaceutical formulations), or the compound of formula (I) and the additional therapeutic agent are administered sequentially / separately. If administered sequentially, the compound of formula (I) of the present invention or one or more additional therapeutic agents can be administered first. If administered simultaneously, the one or more additional therapeutic agents may be contained in the same pharmaceutical formulation as the compound of formula (I), or they may be administered in two or more different (separate) pharmaceutical formulations.

[0651] 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 anticancer drugs. The anticancer drugs administered in combination with the compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof can, for example, be selected from: 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 drugs or antimitotic alkaloids); platinum complexes; antitumor antibiotics; alkylating agents (e.g., nitrogen mustards or nitrosoureas); endocrine drugs (e.g., adrenocortical steroids, androgens, antiandrogens, estrogens, antiestrogens, aromatase inhibitors, gonadotropin-releasing hormone agonists, or somatostatin analogs); compounds that target enzymes or receptors of specific metabolic pathways that are overexpressed in tumor cells and / or otherwise involved in deregulation (or misregulation) (e.g., ATP and GTPase inhibitors); Phosphodiesterase inhibitors, histone deacetylase inhibitors, protein kinase inhibitors (such as serine, threonine and tyrosine kinase inhibitors, for example, Abelson protein tyrosine kinase inhibitor) and various growth factor receptors and corresponding kinase inhibitors (for example, 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); methionine; aminopeptidase inhibitors; proteasome inhibitors; cyclooxygenase inhibitors (for example, cyclooxygenase-1 or cyclooxygenase-2 inhibitors); topoisomerase inhibitors (for example, topoisomerase I inhibitors or topoisomerase II inhibitors); poly ADP ribose polymerase inhibitors (PARP inhibitors); epidermal growth factor receptor (EGFR) inhibitors / antagonists; adenosine A 2A Adenosine A receptor antagonist 2B Adenosine receptor antagonist; 2A / A 2B receptor antagonists; and prostaglandin E2 receptor 4 (EP4) antagonists.

[0652] Alkylating agents that can be used as anticancer drugs in combination with the compounds of the present invention can be, for example, nitrogen mustards (such as cyclophosphamide, mechlorethamine (chlormethine), uramustine, melphalan, chlorambucil, ifosfamide, bendamustine or trofosfamide), nitrosoureas (such as carmustine, streptozocin, fotemustine, lomustine, nimustine, Prednimustine, ranimustine or semustine), alkyl sulfonates (such as busulfan, mannosulfan or trooxsulfan), aziridines (such as hexamethylmelamine (altretamine), triethylenemelamine, ThioTEPA (N,N'N'-triethylenethiophosphoramide), carboquinone or triaziquone); hydrazines (such as procarbazine), triazines (such as dacarbazine) or imidazotetrazines (such as temozolomide).

[0653] Platinum complexes that can be used as anticancer drugs in combination with the compounds of the present invention may be, for example, cisplatin, carboplatin, nedaplatin, oxaliplatin, satraplatin or triplatin tetranitrate.

[0654] Cytotoxic drugs that can be used as anticancer drugs in combination with the compounds of the present invention can be, for example, antimetabolites, including folic acid analog antimetabolites (such as aminopterin, methotrexate, pemetrexed or raltitrexed), purine analog antimetabolites (such as cladribine, clofarabine, fludarabine, 6-mercaptopurine (including its prodrug form azathioprine), pentostatin or 6-thioguanine) and pyrimidine analog antimetabolites (such as cytarabine, decitabine, 5-fluorouracil (including its prodrug forms capecitabine and tegafur), floxuridine, gemcitabine, enocitabine or sapacitabine).

[0655] Antimitotic agents that can be used as anticancer drugs in combination with the compounds of the present invention can be, for example, taxanes (such as docetaxel, larotaxel, ortataxel, paclitaxel / taxol, tesetaxel or nab-paclitaxel (such as )), a vinca alkaloid (such as vinblastine, vincristine, vinflunine, vindesine, or vinorelbine), an epothilone (such as epothilone A, epothilone B, epothilone C, epothilone D, epothilone E, or epothilone F), or an epothilone B analog (such as ixabepilone / azaepothilone B).

[0656] Antitumor antibiotics used as anticancer drugs that can be combined with the compounds of the present invention may be, for example, anthracyclines (such as aclarubicin, daunorubicin, doxorubicin, epirubicin, idarubicin, amrubicin, pirarubicin, valrubicin or zorubicin), anthracenediones (such as mitoxantrone or picoanthrone) or antitumor antibiotics isolated from Streptomyces (such as actinomycin (including actinomycin D), bleomycin, mitomycin (including mitomycin C) or plicamycin).

[0657] Tyrosine kinase inhibitors that can be used as anticancer drugs in combination with the compounds of the present invention can be, for example, axitinib, bosutinib, cediranib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib, sorafenib, sunitinib, axitinib, nintedanib, ponatinib, vandetanib or vemurafenib.

[0658] Topoisomerase inhibitors that can be used as anticancer drugs in combination with the compounds of the present invention can be, for example, topoisomerase I inhibitors (such as irinotecan, topotecan, camptothecin, belotecan, rubitecan or lamellarin D) or topoisomerase II inhibitors (such as amsacrine, etoposide, etoposide phosphate, teniposide or doxorubicin).

[0659] PARP inhibitors that can be used as anticancer drugs in combination with the compounds of the present invention can be, for example, niraparib, olaparib, rucaparib, talazoparib, veliparib, pamiparib (BGB-290), BMN-673, CEP 9722, MK 4827, E7016 or 3-aminobenzamide.

[0660] EGFR inhibitors / antagonists that can be used as anticancer drugs in combination with the compounds of the present invention can be, for example, gefitinib, erlotinib, lapatinib, afatinib, neratinib, osimertinib, brigatinib, dacomitinib, vandetanib, pelitinib, canertinib, icotinib, poziotinib, ABT-414, AV-412, PD 153035, PKI-166, BMS-690514, CUDC-101, AP26113, XL647, cetuximab, panitumumab, zalutumumab, nimotuzumab or matuzumab.

[0661] Adenosine A can be used as an anticancer drug in combination with the compounds of the present invention 2A The receptor antagonist can be, for example, ciforadenant, imaradenant, inupadenant, istradefylline, preladenant, SCH-58261, SCH-442416, ST 1535, or ZM241385.

[0662] Adenosine A can be used as an anticancer drug in combination with the compounds of the present invention 2B The receptor antagonist can be, for example, LAS38096 or LAS101057.

[0663] Adenosine A can be used as an anticancer drug in combination with the compounds of the present invention 2A / A 2B The receptor antagonist can be, for example, M1069, etrumadenant, or INCB106385.

[0664] Prostaglandin E2 receptor 4 (EP4) antagonists that can be used as anticancer drugs in combination with the compounds of the present invention can be, for example, DT-9081, grapiprant, palupiprant, BAY-1316957, CJ-42794, ER-819762, GW627368, L-161982, MF498, MF-766, MK-2894 or ONO-AE3-208.

[0665] Other anticancer drugs can also be used in combination with the compounds of the present invention. Anticancer drugs can include biomolecules or chemical molecules, such as TNF-related apoptosis-inducing ligand (TRAIL), tamoxifen, amsacrine, bexarotene, estramustine, irofulven, trabectedin, cetuximab, panitumumab, tositumomab, alemtuzumab, bevacizumab, edrecolomab, gemtuzumab, avocidib, seliciclib, aminolevulinic acid, methyl aminolevulinate, efaproxiral, porfimer sodium, sodium), talaporfin, temoporfin, verteporfin, alitretinoin, tretinoin, anagrelide, arsenic trioxide trioxide), atrasentan, bortezomib, carmofur, celecoxib, demecolcine, elesclomol, elsamitrucin, etoglucid, lonidamine, lucanthone, masoprocol, mitobronitol, mitoguazone, mitotane, oblimersen, omacetaxine, sitimagene, ceradenovec, tegafur, testolactone, tiazofurine, tipifarnib, vorinostat, iniparib, or copanlisib.

[0666] Biopharmaceuticals directed against tumor markers / factors / cytokines involved in cancer or proliferative diseases, such as antibodies, antibody fragments, antibody constructs (e.g., single chain constructs) and / or modified antibodies (e.g., CDR-grafted antibodies, humanized antibodies, "fully human" antibodies, etc.) can also be used in co-therapeutic methods with the compounds of the present invention. Examples of such biomolecules are anti-HER2 antibodies (e.g., trastuzumab, ), anti-CD20 antibodies (such as rituximab, ), anti-CD19 / CD3 constructs and anti-TNF antibodies (see, eg, Taylor PC, Curr Opin Pharmacol, 2003, 3(3):323-328).

[0667] Anticancer drugs that can be used in combination with the compounds of the present invention can be, in particular, immuno-oncology therapeutic agents (such as antibodies (e.g., monoclonal antibodies or polyclonal antibodies), antibody fragments, antibody constructs (e.g., single-chain constructs), or modified antibodies (e.g., CDR-grafted antibodies, humanized antibodies, or "fully human" antibodies) or small molecules) that target CTLA4, PD1, PDL1, TIGIT, TIM3, LAG3, OX40, CSF1R, IDO, CD40, adenosine A 2A Receptor (A 2A ), adenosine A 2B Receptor (A 2B ), A 2A / A 2B, prostaglandin E2 receptor 4 (EP4), or chemokine (CC motif) receptor 8 (CCR8). Such immuno-oncology therapeutics 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), cemiplimab, dostarlimab, spartalizumab, camrelizumab, sintilimab, tislelizumab (tislelizumab), etc. lizumab), 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 bintrafusp alfa), 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 BMJ), S-986016), ieramilimab (or LAG525), encelimab (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 an anti-CCR8 antibody (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 and are described, for example, 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.

[0668] In particular, the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any of the above entities can be administered in combination with an immune checkpoint inhibitor, preferably an antibody (or an antigen-binding fragment or antibody construct thereof) against CTLA-4, PD-1, PD-L1, TIGIT or LAG3. Corresponding preferred examples include, but are not limited to, any one of the anti-CTLA-4 antibodies ipilimumab or tremelimumab, any one of the anti-PD-1 antibodies nivolumab, pembrolizumab, pilimumab, cemiplimab, dotalizumab, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, sepalimab, AMP-224, AMP-514, JTX-4014, INMGA00012 or APE...

Claims

1. The compound of the following formula (I) in: Ring B is non-aromatic C 4-8 a carbocyclic ring or a non-aromatic 4- to 8-membered heterocyclic ring, wherein the ring B is fused with the ring D, wherein the carbocyclic ring or the heterocyclic ring: (i) is replaced by a group R 1 (ii) a group R connected to the same ring carbon atom of the carbocyclic ring or the heterocyclic ring 2A and R 2B and (iii) optionally substituted by one or more groups R Y replace; Ring D is a 5- or 6-membered heteroaromatic ring, said ring D being fused to ring B, wherein said heteroaromatic ring comprises at least one nitrogen ring atom, wherein said heteroaromatic ring is substituted by a group -LA, and wherein said heteroaromatic ring is optionally substituted by one or more groups R X replace; R 1 Selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -(C 0-5 alkylene)-carbocyclic group, and -(C 0-5 Alkylene)-heterocyclic group, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, and said -(C 0-5 The alkylene groups in the heterocyclic group are each optionally substituted by one or more groups R 12 substituted, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, or said-(C 0-5 The one or more -CH2- units contained in the alkylene in the heterocyclic group are each optionally independently selected from -C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, where each R L1 are independently hydrogen or C 1-5 Alkyl groups in which two groups R are attached to the same carbon atom L1 They may also be linked to each other to form, together with the carbon atoms to which they are linked, a cycloalkyl group or a heterocycloalkyl group, And wherein said -(C 0-5 The carbocyclic group in the alkylene)-carbocyclic group and the -(C 0-5 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R 11 replace; Each R 11 Independently selected from 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 group, -(C 0-3 alkylene)-heterocyclic group, and -L Z -R Z wherein said-(C 0-3 The carbocyclic group in the alkylene)-carbocyclic group and the -(C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace; Each R 12 are independently selected from -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 group, heterocyclic group, and -L Z -R Z wherein the carbocyclic group and the heterocyclic group are each optionally substituted by one or more groups R Cyc replace; R 2A and R 2B are connected to each other to form, together with the carbon atoms to which they are connected, a cycloalkyl, a cycloalkenyl, a heterocycloalkyl, or a heterocycloalkenyl, wherein the cycloalkyl, the cycloalkenyl, the heterocycloalkyl or the heterocycloalkenyl is optionally substituted by one or more groups R 21 replace; or R 2A and R 2B Each independently selected from C 1-5 Alkyl, C 2-5 Alkenyl, C 2-5 Alkynyl, -(C 0-5 alkylene)-carbocyclic group, and -(C 0-5 alkylene)-heterocyclic group, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, and said -(C 0-5 The alkylene groups in the heterocyclic group are each optionally substituted by one or more groups R 22 substituted, wherein the alkyl, alkenyl, alkynyl, -(C 0-5 Alkylene)-alkylene in carbocyclic group, or said-(C 0-5 The one or more -CH2- units contained in the alkylene in the alkylene)-heterocyclic group are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and further, wherein the -(C 0-5 The carbocyclic group in the alkylene)-carbocyclic group and the -(C 0-5 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace, Where R 2A and group R Y can also be linked to each other to form, together with the ring atoms to which they are linked, a carbocyclic group or a heterocyclic group, wherein the carbocyclic group or the heterocyclic group is optionally substituted by one or more groups R Cyc replace; Each R 21 Independently selected from 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 group, -(C 0-3 alkylene)-heterocyclic group, and -L Z -R Z wherein said-(C 0-3 The carbocyclic group in the alkylene)-carbocyclic group and the -(C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace; Each R 22 are independently selected from -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 group, heterocyclic group, and -L Z -R Z wherein the carbocyclic group and the heterocyclic group are each optionally substituted by one or more groups R Cyc replace; Each R X Independently selected from 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 group, -(C 0-3 alkylene)-heterocyclic group, and -L Z -R Z wherein said-(C 0-3 The carbocyclic group in the alkylene)-carbocyclic group and the -(C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace; Each R Y Independently selected from 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 group, -(C 0-3 alkylene)-heterocyclic group, and -L Z -R Z wherein said-(C 0-3 The carbocyclic group in the alkylene)-carbocyclic group and the -(C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc replace; in, Any two groups R attached to the same ring carbon atom Y (i) may also be linked to each other to form, together with the carbon atoms to which they are linked, a cycloalkyl group or a heterocycloalkyl group, wherein the cycloalkyl group or the heterocycloalkyl group is optionally substituted by one or more groups R Cyc substitution; or (ii) may mutually form a group =O; L is selected from -CO-, -SO- and -SO2-; The group A is -N(-R N )-R N or a heterocyclic group, wherein the heterocyclic group is linked to the group L via a ring nitrogen atom, and wherein the heterocyclic group is optionally substituted by one or more groups R A replace; Each R N are independently selected from 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(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 group, and -(C 0-8 Alkylene)-heterocyclic group, wherein the C 1-8 Alkyl, the C 2-8 Alkenyl, the C 2-8 Alkynyl, and the above C 0-8 Alkylene and C 1-8 The one or more -CH2- units contained in any one of the alkylene groups are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, wherein the -(C 0-8 The carbocyclic group in the alkylene)-carbocyclic group and the -(C 0-8 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc substituted, and at least one group R N It is not hydrogen; Each R A Independently selected from 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 group, -(C 0-3 alkylene)-heterocyclic group, and -L Z -R Z wherein said-(C 0-3 The carbocyclic group in the alkylene)-carbocyclic group and the -(C 0-3 The heterocyclic groups in the alkylene)-heterocyclic group are each optionally substituted by one or more groups R Cyc and further, any two groups R connected to the same carbon atom of group A A They may also be linked to each other to form, together with the carbon atoms to which they are linked, a cycloalkyl group or a heterocycloalkyl group, wherein the cycloalkyl group or the heterocycloalkyl group is optionally substituted by one or more groups R Cyc replace; Each R Cyc Independently selected from 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)(-OC 1-5 alkyl), -P(=O)(-OC 1-5 Alkyl)(-OC 1-5 Alkyl), -(C 0-3 Alkylene)-cycloalkyl, -(C 0-3 alkylene)-heterocycloalkyl, and -L Z -R Z ; Each L Z are independently selected from a covalent bond, C 1-7 Alkylene, C 2-7 Alkenylene, and C 2-7 wherein the alkylene, the alkenylene and the alkynylene are each optionally substituted by one or more 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 wherein the one or more -CH2- units contained in the alkylene, alkenylene or alkynylene are each optionally independently selected from -O-, -NH-, -N(C 1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-; and Each R Z are independently selected from -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, wherein the aryl, the heteroaryl, the cycloalkyl, and the heterocycloalkyl are each optionally substituted by one or more 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), -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), carbocyclyl, and heterocyclyl, wherein the carbocyclyl and the heterocyclyl are each optionally substituted by one or more 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), -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), and -SO2-(C 1-5 Alkyl) group substitution; The conditions are: – If Ring B is a pyrrolidinyl ring and Ring D is a pyridinyl ring, R 2A and R 2B are linked to each other to form a cyclopropyl group together with the carbon atoms to which they are linked, L is -CO-, and group A is morpholin-4-yl, then R 1 Not 5-R 11 -pyrimidin-2-yl or acetyl; – If 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 Each is a methyl group, R 1 is optionally substituted by one or more groups R 11 Substituted phenyl, L is -CO-, and group A is -NH-R N , then R N is not a heterocycloalkyl group containing one oxidized sulfur ring atom, wherein all other ring atoms are carbon atoms, and said heterocycloalkyl group is substituted with methyl; – If ring B and ring D together form 3-R X -4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl ring, R X Yes -OH, R 2A and R 2B One of them is methyl, R 2A and R 2B The other one is -CON(-CH3)2, R 1 is methyl, L is -CO-, and group A is -NH-R N , then R N is not 4-fluorobenzyl; and – If 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 group A is -NH-R N , and R 1 is -CH2-phenyl or -CH2-pyridyl, wherein the phenyl group in the -CH2-phenyl group and the pyridyl group in the -CH2-pyridyl group are each optionally substituted by one or more groups R 11 Replace, then R 2A and R 2B It’s not meth; or a pharmaceutically acceptable salt or solvate thereof.

2. The compound of claim 1, wherein ring B is a non-aromatic 4- to 8-membered heterocyclic ring, and the ring B is optionally substituted by one or more groups R Y replace.

3. The compound of claim 1 or 2, wherein ring B is a pyrrolidinyl ring or a piperidinyl ring, wherein the pyrrolidinyl ring or the piperidinyl ring is optionally substituted with one or more groups R Y substituted, and wherein the group R 1 is connected to a nitrogen ring atom of the pyrrolidinyl ring or the piperidinyl ring.

4. The compound according to any one of claims 1 to 3, wherein ring B is a group of the formula: It is optionally substituted by one or two radicals R Y replace.

5. The compound of any one of claims 1 to 4, wherein ring D is a 6-membered heteroaromatic ring containing one or two nitrogen ring atoms, with all remaining ring atoms being carbon atoms, and wherein the heteroaromatic ring is optionally substituted with one or more radicals R X replace.

6. The compound of any one of claims 1 to 5, wherein ring D is a pyridyl ring or a pyrazinyl ring, wherein the pyridyl ring or the pyrazinyl ring is optionally substituted by one or more groups R X replace.

7. The compound according to any one of claims 1 to 6, wherein ring D is optionally substituted with one or more groups R X A substituted pyrazinyl ring, wherein the pyrazinyl ring is fused to Ring B via its ring carbon atoms 2 and 3.

8. The compound of any one of claims 1 to 7, wherein the compound of formula (I) has the following structure:

9. The compound of any one of claims 1 to 8, wherein R 1 Yes-L 1 -Carbocyclic or -L 1 -heterocyclic group, wherein the -L 1 -Carbocyclic group or the -L 1 The heterocyclic group in the heterocyclic group is optionally substituted by one or more groups R 11 Replace, where each L 1 are independently selected from a bond, -C(R L1 )(R L1 )-, -O-, -S-, -SO-, -SO2-, -CO-, and -N(R L1 )-, where each R L1 are independently hydrogen or C 1-5 alkyl, and further, wherein the two groups R attached to the same carbon atom L1 They may also be linked to each other to form a cycloalkyl or heterocycloalkyl group together with the carbon atoms to which they are linked.

10. The compound of any one of claims 1 to 9, wherein R 1 is optionally substituted by one or more groups R 11 Substituted phenyl.

11. The compound of any one of claims 1 to 10, wherein R 1 It is 3-R 11 -4-R 11 -phenyl or 3-R 11 -4-R 11 -5-R 11 -phenyl, where each R 11 independently selected from halogen, C 1-5 Haloalkyl, and C 1-5 alkyl; Preferably, wherein R 1 Selected from 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, and 4-chloro-3,5-difluoro-phenyl.

12. The compound of any one of claims 1 to 11, wherein R 2A and R 2B are connected to each other to form, together with the carbon atoms to which they are connected, a cycloalkyl group or a heterocycloalkyl group, wherein the cycloalkyl group or the heterocycloalkyl group is optionally substituted by one or more groups R 21 replace.

13. The compound of any one of claims 1 to 12, wherein R 2A and R 2B are connected to each other to form, together with the carbon atoms to which they are connected, a cyclopentyl group or a tetrahydrofuranyl group, wherein the cyclopentyl group or the tetrahydrofuranyl group is optionally substituted by one or more groups R 21 replace.

14. The compound of any one of claims 1 to 11, wherein R 2A and R 2B 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, wherein the alkyl or the -(C 0-5 Alkylene)-cycloalkyl, the-(C 0-5 Alkylene)-aryl, the-(C 0-5 Alkylene)-heterocycloalkyl, or said-(C 0-5 The alkylene in any one of the heteroaryl)-alkylene groups is optionally substituted by one or more 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, wherein the -(C 0-5 alkylene)-cycloalkyl in the cycloalkyl group, the -(C 0-5 alkylene) aryl, the aryl group in the -(C 0-5 The heterocycloalkyl group in the -(C 0-5 The heteroaryl groups in the alkylene)-heteroaryl group are each optionally substituted by one or more 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.

15. The compound of any one of claims 1 to 11 or 14, wherein R 2A and R 2B Each independently is C 1-5 alkyl; Preferably, wherein R 2A and R 2B Each is a methyl group.

16. The compound of any one of claims 1 to 15, wherein L is -CO-.

17. The compound of any one of claims 1 to 16, wherein group A is a heterocycloalkyl group connected to group L via a ring nitrogen atom, wherein the heterocycloalkyl group is optionally substituted by one or more groups R A replace.

18. The compound of any one of claims 1 to 17, wherein group A is 2,2-dimethyl-piperazin-1-yl, wherein the piperazinyl in the 2,2-dimethyl-piperazin-1-yl is optionally substituted by one or more groups R A replace; Preferably, group A is 2,2-dimethyl-4-(5-carboxy-4,6-dimethyl-pyridin-2-yl)piperazin-1-yl.

19. The compound of claim 1, wherein the compound is selected from: 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]pyridin]-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]pyridin]-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; 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 ester; 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; 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; 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; 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]pyridin-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; 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; 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; 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-carboxylic acid ethyl ester; 1-(1-(4-chloro-3-fluorophenyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carbonyl)piperidine-4-carboxylic acid; 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; 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; 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; 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 ester; 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; 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 ester; 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; 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 ethyl ester; 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; 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-carboxamido)butanoic acid; 3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)butanoic acid methyl ester; (R)-3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)butanoic acid methyl ester; (R)-3-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)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; 6-((2-(1-(4-chloro-3-fluorophenyl)-N,3,3-trimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-5-carboxamido)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-carboxamido)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; 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; 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; 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-carboxylic acid ethyl ester; (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; 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 ester; 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; 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 methyl ester; 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; 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 ethyl ester; 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; 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; 6-(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-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-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-ene-5'-carbonyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinic acid; 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; 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; (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 ethyl ester; (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; 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; 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; 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; 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 methyl ester; 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; 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 ester; 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; 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; 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)nicotinate hydrochloride; 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; 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; 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; 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]hept-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]hept-2-yl)nicotinic acid; 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; 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; 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]pyridin-1-yl)nicotinoyl)-3,3-dimethylpiperazin-1-yl)-2,4-dimethylnicotinate; 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]pyridin-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; 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; 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 ethyl ester; (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; 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 ester; 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; 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 ester; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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 ester; 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; 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; 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; 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; 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; 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; 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; 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 ester; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 6-(4-((1s,3s)-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-((1s,3s)-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; 6-(4-((1r,3r)-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-((1r,3r)-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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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 methyl ester; 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-triazatriacontriadecyl)-N-methylpalmitamide; 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; 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; 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; 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; 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; 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; 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; 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; 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; Or a pharmaceutically acceptable salt or solvate of any one of the above compounds.

20. A compound as defined in any one of claims 1 to 19, wherein the compound is bound to the membrane anchor via a linker.

21. A pharmaceutical composition comprising a compound according to any one of claims 1 to 20 and a pharmaceutically acceptable excipient.

22. A compound according to any one of claims 1 to 20 or a pharmaceutical composition according to claim 21 for use in treating or preventing 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.

23. The compound of any one of claims 1 to 20 or the pharmaceutical composition of claim 21 for treating or preventing 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, nonalcoholic steatohepatitis, obesity, diabetes, fatty 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 lung disease, pulmonary fibrosis, interstitial lung disease associated with rheumatoid arthritis, liver fibrosis, cystic fibrosis, renal fibrosis, peritoneal fibrosis, pancreatic fibrosis, intestinal fibrosis, cardiac fibrosis, skin fibrosis, systemic lupus erythematosus, scleroderma, skin eczema, acne, rosacea, post-inflammatory hyperpigmentation, lichen planus, pruritus, polymyositis, vasculitis, Wegener's granulomatosis, Netherton syndrome, dermatomyositis, uveitis, cirrhosis of the liver, Alzheimer's disease, Parkinson's disease, dust mite allergy, cockroach allergy, or allergic asthma.

24. A compound according to any one of claims 1 to 20 or a pharmaceutical composition according to claim 21 for use in treating or preventing cancer.

25. The compound for use according to claim 24 or the pharmaceutical composition for use according to claim 24, wherein the cancer is selected from colorectal cancer, colon cancer, gastric 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.

26. The compound for use according to claim 24 or 25 or the pharmaceutical composition for use according to claim 24 or 25, wherein the compound or the pharmaceutical composition is administered in combination with one or more anti-cancer drugs.

27. An anticancer drug for treating or preventing cancer, wherein the anticancer drug is administered in combination with the compound of any one of claims 1 to 20 or the pharmaceutical composition of claim 21.

28. The compound for use according to claim 26, or the pharmaceutical composition for use according to claim 26, or the anti-cancer drug for use according to claim 27, wherein the one or more anti-cancer drugs are selected from immune checkpoint inhibitors.

29. The compound for use according to claim 28, the pharmaceutical composition for use according to claim 28, or the anti-cancer drug for use according to claim 28, wherein the immune checkpoint inhibitor is selected from anti-CTLA-4 antibodies, anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-TIGIT antibodies, and anti-LAG3 antibodies.

30. The compound for use according to claim 28 or 29, or the pharmaceutical composition for use according to claim 28 or 29, or the anticancer drug for use according to claim 28 or 29, wherein the immune checkpoint inhibitor is selected from ipilimumab, tremelimumab, nivolumab, pembrolizumab, pilimumab, cemiprilimumab, dotalimumab, spartalizumab, carrelizumab, sintilimab, tislelizumab, toripalimab, sepalimab, AMP-224, AMP-514, JTX-4014, INCMGA00012, APE02058, atezolizumab, avelumab, durvalumab, KN035, CK-301, BMS-936559, MEDI4736, MPDL3280A, MDX-1105, MEDI6469, bintrafusp alfa, tisleliumab, vembryomab, dovanalimumab, etilizumab, BMS-986207, EOS-448, COM902, ASP8374, SEA-TGT, BGB-A1217, IBI-939, M6223, relalizumab, elalimumab, ansarizumab, tepolizumab, REGN3767, FS118, IMP701, and IMP731.

31. Use of a compound as defined in any one of claims 1 to 20 as a PAR-2 ​​inhibitor in vitro.

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