Somatostatin receptor antagonist compounds and methods of using the same

Abstract

To provide a long-term therapeutic approach for the prevention of hypoglycemia.SOLUTION: A somatostatin receptor antagonist compound having the structure of Formula I is provided. The compound may be useful in the prevention or treatment of hypoglycemia.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 62 / 293,216, filed February 9, 2016, which is incorporated by reference herein for all purposes as if fully set forth herein.

[0002] The present invention relates to compounds that are somatostatin receptor antagonists. More particularly, the present invention relates to cyclic peptides, and more particularly to cyclic octapeptides that are somatostatin receptor antagonists. [Background technology]

[0003] Somatostatin receptors are ubiquitously expressed in most tissues of the body. Five different subtypes of somatostatin receptors have been discovered. The localization of particular receptor subtypes on different tissues allows specific receptor antagonists to exert specific inhibitory effects.

[0004] A series of structure-activity relationship (SAR) studies on the 14-amino acid form of somatostatin (SST-14) and its analogs (Freidinger, RM, et al., International Journal of Peptide and Protein Research 23(2):142-50, 1984; Pattaroni, C., et al., International Journal of Peptide and Protein Research 36(5):401-17, 1990; Weber, DF, et al., Life Sciences 34(14):1371-8, 1984) have revealed that the four amino acid sequence Phe 7 -Trp 8 -Lys 9 -Thr 10 (residues 7-10 of SST-14) have been reported to be important for somatostatin binding and activity. 8 -Lys 9While the cysteine residues always appear in the somatostatin receptor, it has been reported that slight modifications may occur at positions 7 and 10 (Patel, YC, Frontiers in neuroendocrinology 20(3):157-98, 1999). Furthermore, cyclization (via Cys-Cys pairs at positions 3 and 14) mimics a β-turn in a manner favorable for binding to the SST receptor, apparently stabilizing the conformation of these residues (Veber, DF, et al., Life sciences 34(14):1371-8, 1984; Veber, DF, et al., Nature 280(5722):512-4, 1979). Based on these findings, several somatostatin agonist analogs have been developed over the past several decades, and some agonists are clinically used to treat glandular tumors. Octreotide (Novartis) and lanreotide (Ipsen) are indicated for the treatment of acromegaly (growth hormone adenoma) and thyrotroph adenoma, as well as for the management of certain neuroendocrine tumors in the pancreas (e.g., carcinoid tumors). The newer agonist, pasireotide (Novartis), is also used clinically to treat Cushing's disease (corticotroph adenoma) (Boscaro, M., et al., The Journal of Clinical Endocrinology and Metabolism 94(1):115-22, 2009), (see www.signifor.com). Bass et al. (in American Cyanamid) (Bass, RT, et al., Molecular pharmacology 50(4):709-15, 1996) reported that substitution of D-cysteine at the equivalent position to residue 3 of SST-14 resulted in an analog with antagonist activity. Since then, antagonists have been developed that bind to various SST receptor subtypes with different affinities.

[0005] One approach to reducing hypoglycemia is to inhibit somatostatin receptors, which are found in the pancreas, adrenal glands, and hypothalamus of the brain and are involved in counter-regulating hormone release. Somatostatin receptor type 2 (SSTR2) is found in these tissues. In the pancreas, SSTR2 is found almost exclusively on glucagon-secreting α-cells in rodents (Rossowski, W. and Coy, D., Biochemical and Biophysical Research Communications 205:341-346, 1994; Strowski, M., et al., Endocrinology 141:111-117, 2000). Similarly in humans, somatostatin exerts its inhibitory effect on glucagon secretion via SSTR2 found on alpha cells (Kumar, U., et al., Diabetes 48:77-85, 1999; Reubi, J., et al., J. Clin. Endocrinol. Metab. 83:3746-3749, 1998), while the receptor is also expressed in beta cells (Reubi, J., et al., J. Clin. Endocrinol. Metab. 83:3746-3749, 1998), where it is involved in the regulation of insulin secretion. In the adrenal gland, SSTR2 has been widely identified in the adrenal medulla of animals and humans (Kimura, N., et al., Endocrine Journal 48:95-102, 2001; Maurer, R. and Reubi, J., Molecular and Cellular Endocrinology 45:81-90, 1986).Somatostatin has been shown to inhibit the acetylcholine-stimulated release of epinephrine from the adrenal medulla (Role, L., et al., Neuroscience 6:1813-1821, 1981; Mizobe, F., et al., Brain Research 178:555-566, 1979), a mechanism by which epinephrine is released during hypoglycemia (Havel P. and Taborsky, GJ, Stress-induced activation of the neuroendocrine system and its effects on carbohydrate metabolism. In Ellenberg and Rifkin's Diabetes Mellitus. Porte Jr D, Sherwin R, Baron A, Eds. New York, McGraw-Hill, 2003, pp. 127-149). SSTR2 is also found in the hypothalamus of the brain (Fehlmann D., et al., Journal of Physiology (Paris) 94:265-281, 2000; Lanneau C., et al., European Journal of Neuroscience 10:204-212, 1998), where somatostatin also has an inhibitory effect on hormones involved in hypoglycemic counterregulation.

[0006] The use of SSTR2 antagonism to prevent hypoglycemia has been demonstrated in an STZ rat model, where glucagon responses to hypoglycemia, absent in diabetic rats, can be restored by administration of an SSTR2 antagonist (Yue JT, et al., Diabetes 61(1):197-207, 2012). In this experiment, not only was the glucagon response restored, but the corticosterone response, which was also absent in diabetic rats, was also improved by hypoglycemia after treatment with an SSTR2 antagonist. Furthermore, restoration of counterregulatory responses corresponds to the prevention or reduction of the severity of hypoglycemia in similar rats administered insulin doses to induce hypoglycemia (Yue JT, et al., Diabetes 62(7):2215-2222, 2013).

[0007] Somatostatin levels are elevated in the pancreas of diabetic animals (Rastogi, K., et al., Endocrinology 126:1096-1104, 1990; Rastogi, K., et al., Canadian Journal of Physiology and Pharmacology 71:512-517, 1993), as well as in diabetic humans (Orci, L., et al., Proceedings of the National Academy of Sciences USA 73:1338-1342, 1976). In streptozotocin (STZ)-induced diabetic rats, (i) hyperplasia and hypertrophy of somatostatin-containing delta cells in the pancreas (Orci, L., et al., Proceedings of the National Academy of Sciences USA 73:1338-1342, 1976), (ii) increased expression of pancreatic prosomatostatin mRNA (Brubaker, P., et al., Endocrinology 124:3003-3009, 1989; Shi, Z., et al., Endocrinology 137:3193-3199, 1996), and (iii) increased pancreatic somatostatin (Inouye, K., et al., American Journal of Physiology, Endocrinology and Metabolism 282:E1369-E1379, 2002), and (iv) a dispersion of somatostatin-secreting delta cells in the central part of the islet cells (Rossowski, W. and Coy, D., Biochemical and Biophysical Research Communications 205:341-346, 1994). It has been reported that excessive somatostatin may inhibit glucagon release during hypoglycemia (Rastogi, K., et al., Endocrinology 126:1096-1104, 1990). Furthermore, it has been well documented that somatostatin inhibits the stimulated secretion of pancreatic glucagon.In STZ-induced diabetic rats, both proglucagon and prosomatostatin gene expression are significantly increased (Inouye, K., et al., American Journal of Physiology, Endocrinology, and Metabolism 282:E1369-E1379, 2002). This increase in somatostatin levels is observed in diabetic rats during both normoglycemia (i.e., normal blood glucose levels) and hypoglycemia (Shi, Z., et al., Endocrinology 137:3193-3199, 1996). Plasma somatostatin levels also increase during normoglycemia and hypoglycemia in diabetic rats (Shi, Z., et al., Endocrinology 137:3193-3199, 1996). However, despite the increased proglucagon gene expression, plasma glucagon levels do not increase during hypoglycemia in diabetic rats, likely due in part to the significantly elevated somatostatin levels.

[0008] In isolated and isolated perfused islets, the somatostatin receptor type 2 (SSTR2) selective antagonist DC-41-33, also known as PRL-2903, dose-dependently increases glucagon secretion in response to arginine stimulation, and subsequent addition of somatostatin dose-dependently reverses the effect of the SSTR2 antagonist (Cejvan, K., et al., Diabetes 51 Suppl 3:S381-S384, 2002; Cejvan, K., et al., Diabetes 52:1176-1181, 2003).

[0009] In isolated perfused pancreases from nondiabetic rats, this antagonist enhances glucagon secretion without affecting insulin secretion (Cejvan, K., et al., Diabetes 52:1176-1181, 2003). Similar findings have been demonstrated in rat and human pancreatic tissue slices perfused under hypoglycemic conditions with or without an SSTR2 antagonist (Karimian N., et al., Diabetes 62(8):2968-2977, 2013). It can also reverse the inhibitory effects of glucose-dependent insulinotropic polypeptides, i.e., GIP and GIP-(1-30)NH2, and glucagon-like polypeptide, i.e., GLP-1(7-36)NH2, on pentagastrin-stimulated gastric acid secretion in non-diabetic rats (Rossowski, W., et al., British Journal of Pharmacology 125:1081-1087, 1998). Somatostatin receptor antagonists are described in U.S. Pat. No. 4,508,711 (April 1985, Coy et al.) and U.S. Pat. No. 5,846,934 (December 1998, Bass et al.) (Hocart, SJ, et al., Journal of medicinal chemistry 42(11):1863-71, 1999; Rajeswaran, WG, et al., Journal of medicinal chemistry 44(8):1305-11, 2001).

[0010] Currently available primary pharmacological treatments for hypoglycemia are based on various IV glucose or dextrose preparations and are therefore considered reactive rather than true management strategies. While numerous commercially available glucagon products exist (e.g., GlucaGen®, Novo Nordisk), these are rescue approaches, typically administered IV or SC in emergency situations because the patient is unconscious. Importantly, glucagon must also be administered carefully to avoid overstimulating glucose production (which differs from the normal endogenous glucagon response). These therapies do not aim to reduce the incidence of hypoglycemia; rather, they are intended as rescue therapies for severe hypoglycemia, and they are not expected to reduce patient anxiety about the possibility of experiencing a hypoglycemic event. Preventive therapies are needed to reduce or eliminate this troubling problem and enable insulin-dependent diabetes patients to more proactively manage their blood glucose levels, resulting in comprehensive improvements in long-term health outcomes. Therefore, there is a real and strong demand for the development of long-term therapeutic approaches for the prevention of hypoglycemia. Summary of the Invention

[0011] The present invention is based, in part, on novel cyclic peptides that exhibit somatostatin receptor (SSTR) antagonist activity. The cyclic peptides of the invention are often selective for a particular SSTR, such as SSTR2. The invention is also based, in part, on novel amino acids that can be used in the cyclic peptides of the invention.

[0012] In an exemplary embodiment of the invention, a compound of Formula I: [ka] Formula I or a salt thereof, wherein: R C is OH or NHR 16 where R 16 is H or C optionally substituted with one or more substituents 1~6 is alkyl, RN teeth, (i) H, (ii) C 1~6 Alkyl, (iii)-C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (iv) -C(O)C 1~6 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C optionally substituted with one or more substituents 1~6 alkyl), (v)-C(O)C 1~6 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 20 is H or C 1~6 alkyl), (vi)-C(O)C 1~6 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vii)-C(O)C 1~6 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii) -C(O)C 1~6 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and (ix)-S(O)2R 26 (In the formula, R 26 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents. is selected from the group consisting of R 1 is C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 1~6 Alkyl, C 6~10 Aryl, -C 1~6Alkylene (C 6~10 C of aryl) 6~10 Aryl, 5- to 10-membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, where —C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 The alkylene is optionally substituted with one or more substituents; R 3 teeth, (i) C optionally substituted with one or more substituents 6~10 aryl, (ii) a 5- to 10-membered heteroaryl optionally substituted with one or more substituents; (iii)-C 1~6 Alkylene (C 6~10 aryl) (wherein C 6~10 Aryl is optionally substituted with one or more substituents, where C 1~6 alkylene optionally substituted with one or more substituents; (iv)-C 1~6 alkylene(5-10 membered heteroaryl), wherein the 5-10 membered heteroaryl is optionally substituted with one or more substituents, wherein C 1~6 alkylene optionally substituted with one or more substituents; (v)-C 1~6 Alkylene-NR 27 C(O)R 28 (In the formula, R 27 is H or C 1~6 is alkyl, R 28 is C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, and -NR 29 R 30 wherein C is selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; where R 29 and R 30 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vi)-(C 6~10 (arylene)-C(O)NR 31 R 32 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 31 R 32 (In the formula, R 31 and R 32 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vii)-(C 6~10 Arylene)-NR 33 R 34 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 33 R 34 (In the formula, R 33 and R 34 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 35 , -C(O)NR 36 R 37 , and -SO2R 38 wherein C is independently selected from the group consisting of 1~6Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 35 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents; R 36 and R 37 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 38 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii)-(C 6~10 Arylene)-SO2NR 39 R 40 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 39 R 40 (In the formula, R 39 and R 40 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ix)-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 41 R 42 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 41 R 42 (In the formula, R 41 and R 42 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 43 , and -C(O)NR 44 R 45 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 43 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 44 and R 45 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (x)-(C 6~10 arylene)-OR46 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 46 (In the formula, R 46 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and (xi)-C 1~6 Alkylene-(C 6~10 arylene)-N(R 47 )-C(O)-CHR 48 -NR 49 R 50 (In the formula, R 47 is H or CH3, and R 48 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 49 and R 50 each of which is independently H, CH3, or acetyl is selected from the group consisting of R 4 teeth, (I C 1~6 Alkylene-N(R 53 )C(O)NR 51 R 52 (In the formula, R 51 and R 52 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 53 is H or C 1~6 alkyl), (ii)-C 1~6 Alkylene-N(R 55 )C(O)R 54 (In the formula, R 54 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 55 is H or C 1~6 alkyl), (iii)-(C 6~10 (arylene)-C(O)NR 56 R 57 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 56 R 57 (In the formula, R 56 and R 57 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (iv)-(C 6~10 arylene)-N(R 59 )C(O)R 58 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 59 )C(O)R 58 (In the formula, R 58 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents, where R 59 is H or C 1~6 alkyl), (v)-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 (In the formula, R 60 and R 61 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 62 is H or C 1~6 alkyl), (vi)-(C 6~10 arylene)-N(R 64 )SO2R 63 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 64 )SO2R 63 (In the formula, R 63 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 64 is H or C 1~6 alkyl), (vii)-(C 6~10 Arylene)-SO2NR 65 R 66 or -C1~6 Alkylene-(C 6~10 Arylene)-SO2NR 65 R 66 (In the formula, R 65 and R 66 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii)-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 (In the formula, R 67 and R 68 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 69 , and -C(O)NR 70 R 71 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 69 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 70 and R 71 Each of these is H, C 1~6Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ix)-(C 6~10 Arylene)-NR 72 R 73 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 72 R 73 (In the formula, R 72 and R 73 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (x)-(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 (In the formula, R 74 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (xi)-C 1~6 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -NR 77 R 78 (In the formula, R 75 is H or CH3, and R 76is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 77 and R 78 each of which is independently H, CH, or acetyl, and (xii)-C 1~6 Alkylene-(C 6~10 Arylene)-CN is selected from the group consisting of R 5 teeth, (i)-NR 79 R 80 (In the formula, R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 or R 79 and R 80 together with the N atom to which they are attached form a 5- to 10-membered heteroaryl or a 5- to 10-membered heterocycloalkyl, where C 1~6 alkyl is optionally substituted with one or more substituents, wherein 5- to 10-membered heteroaryl and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents; R 81 is H, -NH2, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 82 , R 83 , and R 84 Each of these is H, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (ii)-N + R 85 R 86R 87 (In the formula, R 85 , R 86 , and R 87 Each of the is independently C 1~6 alkyl) is selected from the group consisting of n 1 is 1, 2, 3, 4, 5, or 6, and R 6 is C optionally substituted with one or more substituents 1~6 alkyl, and R 8 is C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 1~6 Alkyl, C 6~10 Aryl, -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl, 5- to 10-membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, where —C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 The alkylene is optionally substituted with one or more substituents; R 9 is H or C 1~6 alkyl, and R 10 is H or C 1~6 alkyl, and R 11 is H or C 1~6 alkyl, and R 12 is H or C 1~6 alkyl, and R 13 is H or C 1~6 alkyl, and R 14 is H or C 1~6 alkyl, and R 15 is H or C 1~6 alkyl and L is [ka] wherein X is S or O, and [ka] wherein chiral center *1 is in the S or R configuration, chiral center *2 is in the S or R configuration, chiral center *3 is in the S or R configuration, chiral center *4 is in the S or R configuration, chiral center *5 is in the S or R configuration, chiral center *6 is in the S or R configuration, chiral center *7 is in the S or R configuration, and chiral center *8 is in the S or R configuration, however, i)R C is NH2 and R N is H or -C(O)CH2N3, and R 1 but, [ka] and R 3 but, [ka] and R 5 is NH2, and n 1 is 4 and R 6 is -CH(OH)(CH3), and R 8 but, [ka] and R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 Each of the is H and L is [ka] If R 4 but [ka] and ii)R C is NH2 and R N is H and R 1 but [ka] and R 3 but [ka] and R 5 is NH2, and n 1 is 4 and R 6 is -CH(CH3)2 and R 8 is -CH(OH)(CH3), and R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 Each of the is H and L is [ka] If R 4 but [ka] provided that it is not.

[0013] In an exemplary embodiment of the invention, the compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof, may be for use in the prevention or treatment of hypoglycemia. In an exemplary embodiment of the invention, the hypoglycemia may be insulin-induced hypoglycemia. In an exemplary embodiment of the invention, the compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof, may be for use in the treatment of diabetes.

[0014] In an exemplary embodiment of the present invention, there is provided a pharmaceutical composition comprising a compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In an exemplary embodiment of the present invention, the pharmaceutical composition may be for use in the prevention or treatment of hypoglycemia. In an exemplary embodiment of the present invention, the hypoglycemia may be insulin-induced hypoglycemia. In an exemplary embodiment of the present invention, the pharmaceutical composition may be for use in the treatment of diabetes.

[0015] In an exemplary embodiment of the present invention, a method of inhibiting the activity of the SSTR2 receptor in a subject is provided, the method comprising administering to a subject in need thereof a compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof. In an exemplary embodiment of the present invention, a method of preventing or treating hypoglycemia in a subject is provided, the method comprising administering to a subject in need thereof a compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof. In an exemplary embodiment of the present invention, the hypoglycemia is insulin-induced hypoglycemia. In an exemplary embodiment of the present invention, a method of treating diabetes in a subject is provided, the method comprising administering to a subject in need thereof a compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof.

[0016] In an exemplary embodiment of the invention, there is provided a use of a compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof, for the prevention or treatment of hypoglycemia. In an exemplary embodiment of the invention, the hypoglycemia is insulin-induced hypoglycemia.

[0017] In an exemplary embodiment of the invention, there is provided the use of a compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof, in the treatment of diabetes. In an exemplary embodiment of the invention, there is provided the use of a compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for the prevention or treatment of hypoglycemia. In an exemplary embodiment of the invention, the hypoglycemia is insulin-induced hypoglycemia. In an exemplary embodiment of the invention, there is provided the use of a compound as defined anywhere herein, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for the treatment of diabetes.

[0018] In an exemplary embodiment of the present invention, [ka] [ka] An amino acid selected from the group consisting of:

[0019] Other aspects and features of the present invention will become apparent to those skilled in the art upon review of the following descriptions of specific embodiments of the invention. [Brief explanation of the drawings]

[0020] [Figure 1] FIG. 1 is a schematic diagram of the study design, showing that animals were made diabetic using STZ injection (week 0), followed by insulin pellet implantation to control diabetes (week 1), and then a subsequent hypoglycemic challenge (weeks 2 and 3). [Figure 2] Detailed procedures regarding hypoglycemic challenge (A - Hypoglycemic Challenge 1, B - Hypoglycemic Challenge 2) and timing of measurements and sample collection are shown. [Figure 3]1 is a graph showing blood glucose (BG) values measured over time in STZ-diabetic Sprague Dawley rats treated with either vehicle control, Compound 4, or Compound 24 during hypoglycemic challenge 1. The inset graph provides a measure of the animals' degree of hypoglycemia from the BG versus time curve, as expressed as the area under the curve (AUC) for blood glucose values over time. [Figure 4] 1 is a graph showing the time to onset of hypoglycemia in STZ-diabetic Sprague Dawley rats treated with either vehicle control, Compound 4, or Compound 24 during the first hypoglycemic challenge. [Figure 5] FIG. 4 is a graph showing the data from FIG. 3 presented as a survival curve showing the proportion of rats from each group that became hypoglycemic (defined as a BG threshold of 3.9 mM) as a function of time. [Figure 6] FIG. 4 is a graph showing the data from FIG. 3 presented as a survival curve showing the proportion of rats from each group that developed severe hypoglycemia (defined as a BG threshold of 1.9 mM) as a function of time. [Figure 7A] 1 is a graph showing the glucagon response to hypoglycemia in STZ-diabetic Sprague Dawley rats treated with either vehicle control, Compound 4, or Compound 24 during the first hypoglycemic challenge. [Figure 7B] 1 is a graph showing the glucagon response to hypoglycemia in STZ-diabetic Sprague Dawley rats treated with either vehicle control, Compound 4, or Compound 24 during the first hypoglycemic challenge. [Figure 8] 1 is a graph showing portal vein blood glucagon concentrations during hypoglycemia in STZ-diabetic Sprague Dawley rats treated with either vehicle control, Compound 4, or Compound 24 during the second hypoglycemic challenge. DETAILED DESCRIPTION OF THE INVENTION

[0021] As used herein, "optionally" or "optionally" means that the subsequently described event or circumstance may, but need not, occur, and that the description includes cases where the event or circumstance occurs and cases where it does not occur.

[0022] When items are described as being "independently selected" from a group, each item is selected independently of the other(s). Thus, each item may be the same or different from the other item(s).

[0023] As used herein, the term "substituted" refers to a group in which a non-hydrogen substituent is in place of a hydrogen substituent on a carbon or nitrogen of the group. For example, a substituted alkyl is an alkyl group in which at least one non-hydrogen substituent is in place of a hydrogen substituent on the alkyl group. Non-limiting examples of substituents include halogen, -OH, -NO, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl).

[0024] A group may be substituted with one or more substituents, provided that the substitution does not exceed the group's normal valences and results in a stable compound. For example, when a methyl group (i.e., CH) is substituted, one, two, or three hydrogen atoms on the carbon atom may be replaced with a substituent. When a substituent is attached through a double bond, such as an oxo (=O) substituent, the substituent occupies two available valences, and therefore the total number of other possible substituents is reduced by two. When a group is described as being substituted with a specific maximum number of substituents, the group may be substituted with that specific maximum number of substituents, provided that the substitution does not exceed the group's normal valences and results in a stable compound. Thus, for example, if a group is described as being heteroaryl substituted with up to three substituents, any heteroaryl having fewer than three substitutable positions will only be substituted with at most the same number of substituents as the heteroaryl has substitutable positions. For example, tetrazolyl (having only one substitutable position) will be substituted with at most one substituent. As a further example, if an amino nitrogen is recited as being substituted with at most two substituents, the nitrogen will be substituted with at most two substituents if the amino nitrogen is a primary nitrogen, whereas the amino nitrogen will be substituted with at most only one substituent if the amino nitrogen is a secondary nitrogen. When there are more than one substitutions on a group, each substituent can be the same or different, unless otherwise specified.

[0025] As used herein, unless otherwise specified, the point of attachment of a substituent may be at any suitable position on the substituent. For example, pyridinyl (or pyridyl) may be 2-pyridinyl (or pyridin-2-yl), 3-pyridinyl (or pyridin-3-yl), or 4-pyridinyl (or pyridin-4-yl).

[0026] When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, such substituent may be bonded to any of the substitutable ring-forming atoms in that ring, unless otherwise specified or otherwise implied by context.

[0027] As used herein, the terms "optionally substituted" and "substituted or unsubstituted" may be used interchangeably to indicate that the particular group being described may have no non-hydrogen substituents (i.e., unsubstituted), or that the group may have one or more non-hydrogen substituents (i.e., substituted).

[0028] When substituents are described as being "independently selected" from a group, each substituent is selected independently of the other(s). Thus, each substituent can be the same or different from the other substituent(s).

[0029] As used herein, the terms "halo" or "halogen," alone or as part of another group or substituent, refer to fluorine, chlorine, bromine, or iodine. Fluorine may be represented as F, -F, or fluoro. Chlorine may be represented as Cl, -Cl, or chloro. Bromine may be represented as Br, -Br, or bromo. Iodine may be represented as I, -I, or iodo.

[0030] As used herein, the term "alkyl," alone or as part of another group or substituent, refers to a saturated monovalent aliphatic hydrocarbon radical (i.e., a radical derived from a hydrocarbon by removal of a hydrogen) having the specified number of carbon atoms. Alkyl includes hydrocarbon radicals with straight or branched chains. x~y The term "alkyl" refers to an alkyl group containing from x to y number of carbon atoms in its carbon skeleton, including all individual integers within the ranges inclusive of the integers x and y. For example, "C 1~6 "Alkyl" refers to an alkyl group that contains 1, 2, 3, 4, 5 or 6 carbon atom(s) in its carbon skeleton. Non-limiting examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 3-methylbutyl, 2,3-dimethylpropyl, n-hexyl, and 2,3-dimethylbutyl.

[0031] Alkyl groups may be optionally substituted. Alkyl groups described herein as optionally substituted may be substituted with one or more substituents, which are independently selected unless otherwise indicated. Non-limiting examples of substituents on alkyl groups include halogen, -OH, -NO, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 The alkyl group may be substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituent(s).

[0032] As used herein, the term "alkylene," alone or as part of another group or substituent, refers to a saturated divalent aliphatic hydrocarbon group that can link two other groups together. Alkylene includes hydrocarbon groups with straight or branched chains. The open valences of an alkylene need not be at opposite ends of the chain. "C x~y The term "alkylene" refers to an alkylene group containing x to y number of carbon atoms in its carbon backbone, including all individual integers within the ranges inclusive of the integers x and y. For example, "C 1~6"Alkylene" refers to an alkylene group containing 1, 2, 3, 4, 5, or 6 carbon atoms in its carbon skeleton. Non-limiting examples of alkylene include methylene (-CH-), 1,2-ethylene (-CHCH-), 1,3-propylene (-CHCHCH-), 1,4-butylene (-CHCHCHCH-), -CH(Me)-, and -C(Me)-. Alkylene is defined as -(CH) n - (wherein n is 1, 2, 3, 4, 5, or 6), or - (CR'R'') n’ - (wherein R' and R'' are H or C 1~6 alkyl, and n' is 1, 2, 3, 4, 5, or 6).

[0033] Alkylene groups may be optionally substituted. Alkylene groups described herein as optionally substituted may be substituted with one or more substituents, which are independently selected unless otherwise specified. Non-limiting examples of substituents for alkylene groups include halogen, -OH, -NO, C, and the like. 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 The alkylene group may be substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituent(s).

[0034] As used herein, the term "alkoxy," alone or as part of another group or substituent, refers to a single alkyl group attached to an oxygen atom. The point of attachment of the alkoxy group to the base molecule is through the oxygen atom. An alkoxy group may be depicted as -O-alkyl. An alkoxy group may contain straight or branched chains. "C x~y The term "alkoxy" refers to an alkoxy group containing x to y carbon atoms, including all individual integers within the ranges inclusive of the integers x and y. For example, "C 1~6 The term "alkoxy" refers to an alkoxy group containing 1, 2, 3, 4, 5, or 6 carbon atom(s). Non-limiting examples of alkoxy groups include methoxy, ethoxy, propoxy, butoxy, and hexyloxy.

[0035] As used herein, the term "aryl," alone or as part of another group or substituent, refers to a monocyclic ring or a fused bicyclic or polycyclic ring system, wherein the monocyclic ring contains a conjugated π-electron system, or at least one ring of the fused ring system contains (i) a conjugated π-electron system, and (ii) a ring-forming carbon atom that is the point of attachment to the base molecule. The ring-forming carbon atoms of the monocyclic ring may not be replaced with ring-forming heteroatoms. The ring-forming carbon atoms of the fused ring system may be replaced with ring-forming heteroatoms selected from N, O, and S, but if the fused ring system contains any ring-forming heteroatoms, the ring-forming heteroatoms are not contained within the ring containing the ring-forming carbon atom that is the point of attachment to the base molecule. The monocyclic ring or fused ring system may contain 6 to 14 ring-forming atoms, in which case the ring-forming atoms include both ring-forming carbon atoms and heteroatoms. "C x~y The term "aryl" refers to a monocyclic ring or fused ring system containing x to y number of ring-forming atoms, including all individual integers within the ranges inclusive of the integers x and y. For example, "C 6~10 "Aryl" refers to a monocyclic ring or fused ring system containing 6, 7, 8, 9, or 10 ring-forming atoms. As a further example, if the aryl group contains any ring-forming heteroatoms, "C 6~10"Aryl" refers to a fused ring system containing 6, 7, 8, 9, or 10 ring-forming atoms, in which case the ring-forming atoms include both ring-forming carbon atoms and heteroatoms. Fused bicyclic or polycyclic ring systems include fused ring systems containing (i) one or more aromatic rings, (ii) one or more non-aromatic cycloalkyl rings, (iii) one or more non-aromatic heterocycloalkyl rings, (iv) one or more heteroaromatic rings, or (v) an aromatic ring fused to any combination or subcombination of (i), (ii), (iii), and (iv). The point of attachment of an aryl group to the base molecule is a ring-forming carbon atom. For clarity, when an aryl group is a fused ring system, the point of attachment of the fused ring system to the base molecule is a ring-forming carbon atom of an aromatic ring of the fused ring system, where the aromatic ring does not contain any ring-forming heteroatoms. Non-limiting examples of aryl groups include phenyl, naphthyl, anthracyl, phenanthrenyl, indanyl, indenyl, and tetrahydronaphthyl.

[0036] An aryl group may be optionally substituted. An aryl group described herein as optionally substituted may be substituted with one or more substituents, which are independently selected unless otherwise specified. Non-limiting examples of substituents for an aryl group include halogen, —OH, —NO, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 The aryl group may be substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituent(s).

[0037] As used herein, the term "arylene," alone or as part of another group or substituent, refers to a divalent form of an aryl group, as defined herein. An arylene group may be optionally substituted with one or more substituents, which are independently selected unless otherwise specified. Non-limiting examples of substituents for an arylene group include halogen, -OH, -NO, C, and the like. 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 The arylene group can be substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituent(s).

[0038] As used herein, the term "heteroaryl," alone or as part of another group or substituent, refers to a monocyclic ring or a fused bicyclic or polycyclic ring system, where the monocyclic ring contains a conjugated π-electron system and at least one ring-forming heteroatom selected from N, O, and S, or at least one ring of the fused ring system contains (i) a conjugated π-electron system, (ii) at least one ring-forming heteroatom selected from N, O, and S, and (iii) a ring-forming atom that is the point of attachment to the base molecule. The monocyclic ring or fused ring system can contain 1, 2, 3, 4, 5, or 6 ring-forming heteroatom(s) selected from N, O, and S. The monocyclic ring or fused ring system can contain 5 to 14 ring-forming atoms, in which case the ring-forming atoms include both ring-forming carbon atoms and heteroatoms. The term "xy-membered heteroaryl" refers to a monocyclic ring or fused ring system containing x through y ring-forming atoms (including all individual integers within the range, inclusive, inclusive of the integers x and y). For example, a "5- to 10-membered heteroaryl" refers to a monocyclic ring or fused ring system containing 5, 6, 7, 8, 9, or 10 ring-forming atoms. Fused bicyclic or polycyclic ring systems include fused ring systems containing (i) one or more heteroaromatic rings, (ii) one or more aromatic rings, (iii) one or more non-aromatic cycloalkyl rings, (iv) one or more non-aromatic heterocycloalkyl rings, or (v) a heteroaromatic ring fused to any combination or subcombination of (i), (ii), (iii), (iv), and (v). The point of attachment of the heteroaryl group to the base molecule is through a ring-forming atom. For clarity, when the heteroaryl group is a fused ring system, the point of attachment to the base molecule on the fused ring system is a ring-forming atom of a heteroaromatic ring of the fused ring system.Non-limiting examples of heteroaryl groups include pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, isothiazolyl, thiazolyl, 1,2,3-triazolyl, 1,3,4-triazolyl, 1-oxa-2,3-diazolyl, 1-oxa-2,4-diazolyl, 1-oxa-2,5-diazolyl, 1-oxa-3,4-diazolyl, 1-thia-2,3-diazolyl, 1-thia-2,4-diazolyl, 1-thia-2,5-diazolyl, 1- Thia-3,4-diazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzofuranyl, benzothiophenyl, indolyl, benzimidazolyl, indazolyl, benzotriazolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[4,5-b]pyridinyl, imidazo[4,5-c]pyridinyl, pyrazolo[4,3-d]pyridinyl, pyrazolo[4 ,3-c]pyridinyl, pyrazolo[3,4-c]pyridinyl, pyrazolo[3,4-b]pyridinyl, isoindolyl, indazolyl, purinyl, indolinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrrolo[1-2,b]pyridazinyl, imidazo[1,2-c]pyrimidinyl, quinolinyl, isoquinolinyl, cinnolinyl, azaquinazoline, quinoxalinyl, phthalazinyl, 1,6-naphthyridinyl, 1,7 -naphthyridinyl, 1,8-naphthyridinyl, 1,5-naphthyridinyl, 2,6-naphthyridinyl, 2,7-naphthyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[4,3-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrido[2,3-d]pyrimidinyl, pyrido[2,3-b]pyrazinyl, pyrido[3,4-b]pyrazinyl, pyrimido[5,4-d]pyrimidinyl, pyrazino[2,3-b]pyrazinyl, and pyrimido[4,5-d]pyrimidinyl.

[0039] Heteroaryl groups can be optionally substituted. Heteroaryl groups described herein as optionally substituted can be substituted with one or more substituents, which are independently selected unless otherwise indicated. Non-limiting examples of substituents for heteroaryl groups include halogen, -OH, -NO, C, and the like. 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6Heteroaryl groups can be substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituent(s).

[0040] As used herein, the term "cycloalkyl," alone or as part of another group or substituent, refers to a non-aromatic saturated monocyclic hydrocarbon ring or a spiro-bridged or fused bicyclic or polycyclic hydrocarbon ring system, wherein at least one ring of the ring system (i) is a non-aromatic hydrocarbon ring in which all non-fused ring-forming carbon atoms are saturated, and (ii) contains a ring-forming carbon atom that is the point of attachment to the base molecule. The ring-forming carbon atoms of the ring system may be replaced with ring-forming heteroatoms selected from N, O, and S, but if the ring system contains any ring-forming heteroatoms, the ring-forming heteroatoms are not contained within the ring containing the ring-forming carbon atom that is the point of attachment to the base molecule. The monocyclic ring or spiro-bridged or fused polycyclic ring system contains 5 to 14 ring-forming atoms, and in that case, the ring-forming atoms include both ring-forming carbon atoms and heteroatoms. "C x~y The term "cycloalkyl" refers to a monocyclic ring or a spiro-bridged or fused polycyclic ring system containing x to y number of ring-forming atoms, including all individual integers within the ranges inclusive of the integers x and y. For example, "C 5~10 "Cycloalkyl" refers to a monocyclic ring or a spiro-bridged or fused polycyclic ring system containing 5, 6, 7, 8, 9, or 10 ring-forming atoms. As a further example, if the cycloalkyl group contains any ring-forming heteroatoms, "C" is used. 5~10"Cycloalkyl" refers to a monocyclic ring or a spiro-bridged or fused polycyclic ring system containing 5, 6, 7, 8, 9, or 10 ring-forming atoms, in which case the ring-forming atoms include both ring-forming carbon atoms and heteroatoms. Fused bicyclic or polycyclic ring systems include fused ring systems containing (i) one or more non-aromatic cycloalkyl rings, (ii) one or more aromatic rings, (iii) one or more non-aromatic heterocycloalkyl rings, (iv) one or more heteroaromatic rings, or (v) a non-aromatic cycloalkyl ring fused to any combination or subcombination of (i), (ii), (iii), and (iv). The point of attachment of the cycloalkyl group to the base molecule is a ring-forming carbon atom. For clarity, if the cycloalkyl group is a ring system, the point of attachment of the ring system to the base molecule is a ring-forming carbon atom of the non-aromatic cycloalkyl ring of the fused ring system, where the non-aromatic cycloalkyl ring does not contain any ring-forming heteroatoms. Non-limiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecanyl, octahydropentalenyl, octahydro-1H-indenyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[3.2.1]octanyl, bicyclo[5.2.0]nonanyl, adamantanyl, and decahydronaphthalenyl.

[0041] Cycloalkyl groups can be optionally substituted. Cycloalkyl groups described herein as optionally substituted can be substituted with one or more substituents, which are independently selected unless otherwise indicated. Non-limiting examples of substituents for cycloalkyl groups include halogen, -OH, -NO, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C5~10 Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 Cycloalkyl groups can be substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituent(s).

[0042] As used herein, the term "heterocycloalkyl," alone or as part of another group or substituent, refers to a non-aromatic saturated monocyclic hydrocarbon ring or a spiro-bridged or fused bicyclic or polycyclic hydrocarbon ring system, wherein the monocyclic ring contains at least one ring-forming heteroatom selected from N, O, and S, or at least one ring of the spiro-bridged or fused ring system (i) is a non-aromatic hydrocarbon ring and all non-fused ring-forming atoms are saturated, (ii) contains at least one ring-forming heteroatom selected from N, O, and S, and (iii) contains a ring-forming atom that is the point of attachment to the base molecule. The monocyclic ring or spiro-bridged or fused polycyclic ring system may contain 1, 2, 3, 4, 5, or 6 ring-forming heteroatom(s) selected from N, O, and S. A monocyclic ring or a spiro-bridged or fused polycyclic ring system can contain 5 to 14 ring-forming atoms, which in turn includes both ring-forming carbon atoms and heteroatoms. The term "x- to y-membered heterocycloalkyl" refers to a monocyclic ring or a spiro-bridged or fused polycyclic ring system containing x to y number of ring-forming atoms (including all individual integers within the ranges inclusive of the integers x and y). For example, "5- to 10-membered heterocycloalkyl" refers to a monocyclic ring or a spiro-bridged or fused polycyclic ring system containing 5 to 10 ring-forming atoms. Fused bicyclic or polycyclic ring systems include fused ring systems containing (i) one or more non-aromatic cycloalkyl rings, (ii) one or more aromatic rings, (iii) one or more non-aromatic heterocycloalkyl rings, (iv) one or more heteroaromatic rings, or (v) a non-aromatic heterocycloalkyl ring fused to any combination or subcombination of (i), (ii), (iii), and (iv). The point of attachment of a heterocycloalkyl group to the base molecule is a ring-forming atom. For clarity, if the heterocycloalkyl group is a ring system, the point of attachment of the ring system to the base molecule is a ring-forming atom of a non-aromatic heterocycloalkyl ring of the fused ring system.Non-limiting examples of heterocycloalkyl groups include oxiranyl, thiaranyl, aziridinyl, oxetanyl, thiatanyl, azetidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, 1,4-dioxanyl, 1,4-oxathianyl, morpholinyl, 1,4-dithianyl, piperazinyl, 1,4-azathianyl, oxepanyl, thiepanyl, azepanyl, 1,4-dioxepanyl, 1,4-oxathiepanyl, 1,4-oxazepanyl, 1,4-dithiepanyl, 1,4-thieazepanyl, and 1,4-diazepanyl.

[0043] Heterocycloalkyl groups can be optionally substituted. Heterocycloalkyl groups described herein as optionally substituted can be substituted with one or more substituents, which are independently selected unless otherwise indicated. Non-limiting examples of substituents on heterocycloalkyl groups include halogen, -OH, -NO, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 Heterocycloalkyl groups can be substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituent(s).

[0044] As used herein, the term "-alkylene(aryl)" refers to an aryl group, as defined herein, which is attached to the base compound via an alkylene linker. 1~6 Alkylene (C 6~10 The term "aryl" refers to a C 6~10 Refers to an aryl group, which is C 1~6 The alkylene (aryl) group is linked to the base compound via an alkylene linker. The aryl of the alkylene (aryl) group may be optionally substituted. Aryl groups described herein as optionally substituted may be substituted with one or more substituents, which are independently selected unless otherwise specified. Non-limiting examples of substituents on the aryl or alkylene group include halogen, -OH, -NO, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 The aryl and alkylene groups may each be substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituent(s).

[0045] As used herein, the term "-alkylene(heteroaryl)" refers to a heteroaryl group, as defined herein, which is attached to the base compound via an alkylene linker. 1~6 The term "alkylene(5-10 membered heteroaryl)" refers to a 5-10 membered heteroaryl group, as defined herein, including C 1~6The heteroaryl of the -alkylene(heteroaryl) may be optionally substituted. Heteroaryl groups described herein as optionally substituted may be substituted with one or more substituents, which are independently selected unless otherwise specified. Non-limiting examples of substituents on heteroaryl or alkylene groups include halogen, -OH, -NO, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, oxo(=O), -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6The heteroaryl and alkylene groups may each be substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituent(s).

[0046] As used herein, the symbols [ka] indicates the point at which the represented moiety is attached to the rest of the molecule. This symbol is sometimes referred to as the point of attachment. The point of attachment may also be represented by a dash "-", e.g., -Br.

[0047] The present invention is based, at least in part, on cyclic peptides that are somatostatin receptor (SSTR) antagonists. The cyclic peptides of the invention are often selective for a particular SSTR, such as SSTR2.

[0048] An exemplary embodiment of the present invention is a compound of formula II: [ka] Formula II or a salt thereof, wherein R C is OH or NH2, R N is H, CH3 or acetyl, R 1 is C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, where —C1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 The alkylene is optionally substituted with one or more substituents; R 3 teeth, (i) C optionally substituted with one or more substituents 6~10 aryl, (ii) a 5- to 10-membered heteroaryl optionally substituted with one or more substituents; (iii)-C 1~6 Alkylene (C 6~10 aryl) (wherein C 6~10 Aryl is optionally substituted with one or more substituents, where C 1~6 alkylene optionally substituted with one or more substituents; (iv)-C 1~6 alkylene(5-10 membered heteroaryl), wherein the 5-10 membered heteroaryl is optionally substituted with one or more substituents, wherein C 1~6 alkylene optionally substituted with one or more substituents; (v)-NR 27 C(O)R 28 or -C 1~6 Alkylene-NR 27 C(O)R 28 (In the formula, R 27 is H or C 1~6 is alkyl, R 28 is C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, and -NR 29 R 30 wherein C is selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; where R 29 and R 30 Each of these is H, C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vi)-(C 6~10 (arylene)-C(O)NR 31 R 32 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 31 R 32 (In the formula, R 31 and R 32 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vii)-(C 6~10 Arylene)-NR 33 R 34 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 33 R 34 (In the formula, R 33 and R 34 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 35 , -C(O)NR 36 R 37 , and -SO2R 38 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 35 is C 1~6 Alkyl, C 6~10aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents; R 36 and R 37 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 38 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii)-(C 6~10 Arylene)-SO2NR 39 R 40 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 39 R 40 (In the formula, R 39 and R 40 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ix)-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR41 R 42 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 41 R 42 (In the formula, R 41 and R 42 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 43 , and -C(O)NR 44 R 45 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 43 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 44 and R 45 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (x)-(C 6~10 arylene)-OR 46 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 46 (In the formula, R 46 is H, C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and (xi)-C 1~6 Alkylene-(C 6~10 arylene)-N(R 47 )-C(O)-CHR 48 -NR 49 R 50 (In the formula, R 47 is H or CH3, and R 48 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 49 and R 50 each of which is independently H, CH3, or acetyl is selected from the group consisting of R 4 teeth, (i)-N(R 53 )C(O)NR 51 R 52 or -C 1~6 Alkylene-N(R 53 )C(O)NR 51 R 52 (In the formula, R 51 and R 52 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 53 is H or C 1~6 alkyl), (ii)-N(R 55 )C(O)R 54 or -C 1~6 Alkylene-N(R55 )C(O)R 54 (In the formula, R 54 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 55 is H or C 1~6 alkyl), (iii)-(C 6~10 (arylene)-C(O)NR 56 R 57 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 56 R 57 (In the formula, R 56 and R 57 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (iv)-(C 6~10 arylene)-N(R 59 )C(O)R 58 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 59 )C(O)R 58 (In the formula, R 58 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents, where R59 is H or C 1~6 alkyl), (v)-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 (In the formula, R 60 and R 61 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 62 is H or C 1~6 alkyl), (vi)-(C 6~10 arylene)-N(R 64 )SO2R 63 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 64 )SO2R 63 (In the formula, R 63 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 64 is H or C 1~6 alkyl), (vii)-(C 6~10 Arylene)-SO2NR 65 R 66 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 65 R66 (In the formula, R 65 and R 66 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii)-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 (In the formula, R 67 and R 68 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 69 , and -C(O)NR 70 R 71 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 69 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 70 and R 71 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ix)-(C 6~10 Arylene)-NR 72 R 73 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 72 R 73 (In the formula, R 72 and R 73 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (x)-(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 (In the formula, R 74 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and (xi)-C 1~6 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -NR 77 R 78 (In the formula, R 75 is H or CH3, and R 76is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 77 and R 78 each of which is independently H, CH3, or acetyl is selected from the group consisting of R 5 teeth, (i)-NR 79 R 80 (In the formula, R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 or R 79 and R 80 together with the N atom to which they are attached form a 5- to 10-membered heteroaryl or a 5- to 10-membered heterocycloalkyl, where C 1~6 alkyl is optionally substituted with one or more substituents, wherein 5- to 10-membered heteroaryl and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents; R 81 is H, -NH2, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 82 , R 83 , and R 84 Each of these is H, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (ii)-N + R 85 R 86 R 87 (In the formula, R 85 , R 86 , and R 87Each of the is independently C 1~6 alkyl) is selected from the group consisting of n 1 is 1, 2, 3, 4, 5, or 6, and R 12 is H or CH3, and R 6 is C optionally substituted with one or more substituents 1~6 alkyl, and R 8 is C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, where —C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is optionally substituted with one or more substituents, and L is [ka] wherein X is S or O, and [ka] wherein chiral center *1 is in the S or R configuration, chiral center *3 is in the S or R configuration, chiral center *4 is in the S or R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S or R configuration, and chiral center *8 is in the S or R configuration, however, L [ka] and R 4 is -CH2-(phenylene)-N(H)C(O)NH2, and R 3 is -CH2-(phenyl) or -CH2-(phenylene)-N(H)C(O)R 35 wherein the phenyl of -CH2-(phenyl) is replaced with hydroxy, and wherein R 35 is 2,6-dioxohexahydropyrimidine, and R 5 is NH2, and n 1 is 4 and R 12 is H and R 6 is -CH(OH)(CH3), and R 8 is —CH2-(phenyl) or —CH2-(naphthyl), where the phenyl is substituted with hydroxy; R 1 is not -CH2- (phenyl), provided that the phenyl is replaced with -Cl or -NO2.

[0049] According to another embodiment, there is provided a compound having the structure of Formula II, or a salt thereof, wherein R N , R C , R 1 , R 3 , R 4 , R 5 , R 6 , R 8 , R 12 , n 1, L, chiral center *1, chiral center *3, chiral center *4, chiral center *5, chiral center *6, and chiral center *8 are as defined anywhere herein, except that the compound is (i) H-Cpa-cyclo[DCys-Tyr-D-4Aph(Cbm)-Lys-Thr-Cys]-2Nal-NH2, (ii) H-Cpa-cyclo[D Cys-Tyr-D-4Aph(Cbm)-Lys-Thr-Cys]-D-Tyr-NH2, (iii)H-pNO2-Phe-cyclo[DCys-Tyr-D-4Aph(Cbm) -Lys-Thr-Cys]-2Nal-NH2, (iv)H-Cpa-cyclo[DCys-4Aph(Hor)-D-4Aph(Cbm)-Lys-Thr-Cys]-D-Tyr- NH2, (v)H-pNO2-Phe-cyclo[DCys-Tyr-D-4Aph(Cbm)-Lys-Thr-Cys]-D-Tyr-NH2, (vi)H-pNO2-Phe- Chlo[DCys-4Aph(Hor)-D-4Aph(Cbm)-Lys-Thr-Cys]-D-Tyr-NH2, (vii)H-Cpa-Cyclo[DCys-4Aph(Hor)- D-4Aph(Cbm)-Lys-Thr-Cys]-2Nal-NH, and (viii) H-pNO-Phe-cyclo[DCys-4Aph(Hor)-D-4Aph(Cbm)-Lys-Thr-Cys]-2Nal-NH, wherein DCys and Cys in each of (i), (ii), (iii), (iv), (v), (vi), (vii), and (viii) are [ka] (connected by

[0050] R C and R N Embodiments of the present invention In some embodiments, R C is OH or NHR 16 where R 16 is H or C optionally substituted with one or more substituents 1~6 In other embodiments, R C is OH or NHR 16where R 16 is H or halogen, -OH, -NO2, C 1~6 Alkoxy, and C 6~10 C optionally substituted with one or more substituents each independently selected from the group consisting of aryl 1~6 In some embodiments, R C is OH or NHR 16 where R 16 is H or halogen, -OH, -NO2, and C 1~6 C optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy 1~6 In some embodiments, R C is OH or NHR 16 where R 16 is H or C 1~6 In some embodiments, R C is OH or NHR 16 where R 16 is H or C 1~5 In some embodiments, R C is OH or NHR 16 where R 16 is H or C 1~4 In some embodiments, R C is OH or NHR 16 where R 16 is H or C 1~3 In some embodiments, R C is OH or NHR 16 where R 16 is H or C 1~2 In some embodiments, R C is OH or NHR 16 where R 16 is H or CH. In some embodiments, R C is OH or NH. In other embodiments, R C is OH. In other embodiments, R C is NH2.

[0051] In some embodiments, R N teeth, (i) H, (ii) C 1~6 Alkyl, (iii)-C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (iv) -C(O)C 1~6 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C optionally substituted with one or more substituents 1~6 alkyl), (v)-C(O)C 1~6 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 20 is H or C 1~6 alkyl), (vi)-C(O)C 1~6 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vii)-C(O)C 1~6 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii) -C(O)C 1~6 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and (ix)-S(O)2R 26 (In the formula, R 26 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents. is selected from the group consisting of:

[0052] In other embodiments, R N teeth, (i) H, (ii) C 1~6 Alkyl, (iii)-C(O)R 17 (In the formula, R 17 is C1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) -C(O)C 1~6 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v)-C(O)C 1~6 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi)-C(O)C 1~6 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii)-C(O)C 1~6 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (viii) -C(O)C 1~6 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (ix)-S(O)2R 26 (In the formula, R 26 is C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl) is selected from the group consisting of:

[0053] In some embodiments, R N teeth, (i) H, (ii) C 1~6 Alkyl, (iii)-C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) -C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v)-C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi)-C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii)-C(O)C 1~3 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) -C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl) is selected from the group consisting of:

[0054] In other embodiments, R N is H, C 1~6 Alkyl, -C(O)R 17 , -C(O)C 1~6 Alkylene-C(O)OR 18 , -C(O)C 1~6 Alkylene-N(R 20 )C(O)R 19 , -C(O)C 1~6 Alkylene-NR 21 R 22 , -C(O)C 1~6 Alkylene-C(O)NR 23 R 24 , and -C(O)C 1~6 Alkylene-S(O)R 25 where R 17 is C 1~6 alkyl or 5-6 membered heteroaryl, R 18 is C 1~6 alkyl, and R 19 is C 1~6 alkyl or C6 aryl, and R 20 , R 21 , R 22 , R 23 and R 24 Each of is H and R 25 is C aryl. In some embodiments, R N is H, C 1~3 Alkyl, -C(O)R 17 , -C(O)C 1~3 Alkylene-C(O)OR 18 , -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 , -C(O)C 1~3 Alkylene-NR21 R 22 , -C(O)C 1~3 Alkylene-C(O)NR 23 R 24 , and -C(O)C 1~3 Alkylene-S(O)R 25 where R 17 is C 1~6 alkyl or 5-6 membered heteroaryl, R 18 is C 1~3 alkyl, and R 19 is C 1~3 alkyl or C6 aryl, and R 20 , R 21 , R 22 , R 23 and R 24 Each of is H and R 25 is C aryl. In some embodiments, R N is H, CH, or acetyl. In some embodiments, R N is H or CH. In other embodiments, R N is H or acetyl. In other embodiments, R N is CH or acetyl. In some embodiments, R N is H. In other embodiments, R N is CH3. In still other embodiments, R N is acetyl.

[0055] Those skilled in the art will understand that the cyclic octapeptides of the present invention may be functionalized at either the C-terminus or the N-terminus by methods known in the art. For example, two methods of functionalization include PEGylation and lipidation (Beilstien J. Org. Chem. 2014, 10, 1197-1212). Functionalized peptides of this nature are also considered within the scope of the present invention. For example, in some embodiments, R C is -N(H)[CH2CH2O] n 16 -R 210 where R 210 is H or C1~6 Those skilled in the art will appreciate that n in the above formula of PEG may be an alkyl. 16 A range of suitable values for n can be easily ascertained. For example, and without limitation, 16 may be an integer from 1 to 40. In some embodiments, R N is -C(O)-[CH2] n 17 -O-[CH2CH2O] n 18 -R 211 where R 211 is H or C 1~6 may be alkyl, n 17 may be an integer from 1 to 6. In another embodiment, n 17 may be 1 or 2. In some embodiments, R N is -C(O)-[CH2CH2O] n 19 -R 211 where R 211 is H or C 1~6 In another embodiment, R N is -[CH2] n 20 -O-[CH2CH2O] n 21 -R 212 where R 212 is H or C 1~6 may be alkyl, n 20 may be an integer from 1 to 6. In other embodiments, n 20 may be 3. In some embodiments, R N is -[CH2CH2O] n 22 -R 212 where R 212 is H or C 1~6 Those skilled in the art will appreciate that n in the above formula of PEG may be an alkyl. 18 , n 19 , n 21 , and n 22 A range of suitable values for n can be easily ascertained. For example, and without limitation, 18 , n 19 , n 21, and n 22 may each independently be an integer from 1 to 40.

[0056] R 1 Embodiments of the present invention In some embodiments, R 1 is C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 1~6 Alkyl, C 6~10 Aryl, -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl, 5- to 10-membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, where —C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 An alkylene is optionally substituted with one or more substituents.

[0057] In some embodiments, R 1 is C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 1~6 Alkyl, C 6~10 Aryl, -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl, 5- to 10-membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene (5- to 10-membered heteroaryl) is halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0058] In some embodiments, R 1 is C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C1~6 Alkyl, C 6~10 Aryl, -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl, 5- to 10-membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is selected from halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, and C 6~10 Optionally substituted with one or more substituents each independently selected from the group consisting of aryl.

[0059] In some embodiments, R 1 is C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, where —C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 An alkylene is optionally substituted with one or more substituents.

[0060] In some embodiments, R 1 is C 6~10 Aryl, 5-10 membered heteroaryl, -C1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene (5- to 10-membered heteroaryl) is halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0061] In some embodiments, R 1 is C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is selected from halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, and C 6~10 Optionally substituted with one or more substituents each independently selected from the group consisting of aryl.

[0062] In some embodiments, R 1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 1~3 Alkylene is C 6~10 aryl. In some embodiments, R 1 -C 1~3 Alkylene (C6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 In other embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 1 -C 1~3 alkylene(5-10 membered heteroaryl), where the 5-10 membered heteroaryl is selected from halogen, hydroxy, -NO2, and C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 1 -C 1~2 alkylene(6-membered heteroaryl), where the 6-membered heteroaryl is selected from halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0063] In some embodiments, R 1 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 Aryl is a group containing halogen, hydroxyl, -NO2, and C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 1 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 The aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxy, and —NO. In some embodiments, R 1 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 The aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen and hydroxy. In some embodiments, R 1 -C 1~2 Alkylene (C 6~10aryl), where C 6~10 The aryl is optionally substituted with halogen. In some embodiments, R 1 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 The aryl is optionally substituted with Cl. In some embodiments, R 1 -C 1~2 alkylene(C6 aryl), where C6 aryl is selected from halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0064] In some embodiments, R 1 is -CH2-phenyl or -CH2-naphthyl, where phenyl or naphthyl is selected from halogen, hydroxy, -NO2, and C 1~6 In other embodiments, R is optionally substituted with one or two substituents each independently selected from the group consisting of alkoxy. 1 is —CH-phenyl or —CH-naphthyl, where phenyl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxyl, and —NO. In some embodiments, R 1 is —CH-phenyl or —CH-naphthyl, where phenyl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen and hydroxyl. In some embodiments, R 1 is —CH-phenyl or —CH-naphthyl, where phenyl is optionally substituted with halogen. In some embodiments, R 1 is —CH2-phenyl or —CH2-naphthyl, where phenyl is optionally substituted with Cl.

[0065] In some embodiments, R 1 is -CH2-phenyl, where phenyl is substituted with halogen, hydroxy, -NO2, and C 1~6In some embodiments, R is optionally substituted with one or two substituents each independently selected from the group consisting of alkoxy. 1 is -CH-phenyl, where phenyl is optionally substituted with one or two substituents each independently selected from the group consisting of halogen, hydroxy, and -NO. In some embodiments, R 1 is —CH-phenyl, where phenyl is unsubstituted. In some embodiments, R 1 is -CH2-phenyl, where phenyl is substituted with halogen, hydroxy, -NO2, and C 1~6 In some embodiments, R is substituted with one or two substituents each independently selected from the group consisting of alkoxy. 1 is -CH-phenyl, where phenyl is substituted with one or two substituents each independently selected from the group consisting of halogen, hydroxy, and -NO. In some embodiments, R 1 is —CH 2 -phenyl, wherein the phenyl is substituted with one or two substituents each independently selected from the group consisting of halogen and hydroxy.

[0066] In some embodiments, R 1 is —CH-phenyl, where phenyl is substituted with one or two substituents each independently selected from the group consisting of —F, —Cl, —Br, and —I. In some embodiments, R 1 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -F. In some embodiments, R 1 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -Cl. In some embodiments, R 1 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -Br. In some embodiments, R 1 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -I. In some embodiments, R 1is -CH-phenyl, where the phenyl is substituted with one substituent that is -F. In some embodiments, R 1 is -CH-phenyl, where the phenyl is substituted with one substituent that is -Cl. In some embodiments, R 1 is -CH-phenyl, where the phenyl is substituted with one substituent that is -Br. In some embodiments, R 1 is -CH2-phenyl, where the phenyl is substituted with one substituent which is -I.

[0067] In some embodiments, R 1 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is hydroxy. In some embodiments, R 1 is -CH-phenyl, where phenyl is substituted with one substituent that is hydroxy. In some embodiments, R 1 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -NO. In some embodiments, R 1 is -CH-phenyl, where the phenyl is substituted with one substituent that is -NO. In some embodiments, R 1 is —CH2-phenyl, where each phenyl is independently C 1~6 In some embodiments, R is substituted with one or two substituents that are alkoxy. 1 is —CH2-phenyl, where each phenyl is independently C 1~3 In some embodiments, R is substituted with one or two substituents that are alkoxy. 1 is -CH2-phenyl, where the phenyl is substituted with one substituent which is methoxy.

[0068] In some embodiments, R 1 teeth [ka] where R 88is H, halogen, hydroxyl or C 1~3 In some embodiments, R 88 is H, halogen, or hydroxyl. In some embodiments, R 88 is H, Cl, or hydroxyl. In some embodiments, R 88 is Cl or hydroxyl. In some embodiments, R 88 is Cl.

[0069] In some embodiments, R 1 -C 1~2 Alkylene (C 10 aryl), where C 10 Aryl is substituted with halogen, hydroxyl and -NO2, as well as C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 1 is -CH2-naphthyl.

[0070] In some embodiments, R 1 is selected from the group consisting of -CH-pyridinyl, -CH-indolyl, -CH-thiophenyl, -CH-thiazolyl, -CH-furanyl, -CH-benzothiophenyl, and -CH-imidazolyl. 1 is -CH-pyridinyl. In some embodiments, R 1 is -CH-indolyl. In some embodiments, R 1 is -CH-thiophenyl. In some embodiments, R 1 is -CH-thiazolyl. In some embodiments, R 1 is -CH-furanyl. In some embodiments, R 1 is —CH-benzothiophenyl. In some embodiments, R 1 is -CH2-imidazolyl.

[0071] R 3 Embodiments of the present invention In some embodiments, R3 teeth, (i) C optionally substituted with one or more substituents 6~10 aryl, (ii) a 5- to 10-membered heteroaryl optionally substituted with one or more substituents; (iii)-C 1~6 Alkylene (C 6~10 aryl) (wherein C 6~10 Aryl is optionally substituted with one or more substituents, where C 1~6 alkylene optionally substituted with one or more substituents; (iv)-C 1~6 alkylene(5-10 membered heteroaryl), wherein the 5-10 membered heteroaryl is optionally substituted with one or more substituents, wherein C 1~6 alkylene optionally substituted with one or more substituents; (v)-C 1~6 Alkylene-N(R 27 )C(O)R 28 (In the formula, R 27 is H or C 1~6 is alkyl, R 28 is C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, and -NR 29 R 30 wherein C is selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 29 and R 30 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vi)-(C 6~10(arylene)-C(O)NR 31 R 32 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 31 R 32 (In the formula, R 31 and R 32 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vii)-(C 6~10 Arylene)-NR 33 R 34 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 33 R 34 (In the formula, R 33 and R 34 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 35 , -C(O)NR 36 R 37 , and -SO2R 38 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 35 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents; R 36 and R 37 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 38 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii)-(C 6~10 Arylene)-SO2NR 39 R 40 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 39 R 40 (In the formula, R 39 and R 40 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ix)-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 41 R 42 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 41 R 42 (In the formula, R 41 and R 42Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 43 , and -C(O)NR 44 R 45 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 43 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 44 and R 45 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (x)-(C 6~10 arylene)-OR 46 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 46 (In the formula, R 46 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and (xi)-C 1~6 Alkylene-(C 6~10arylene)-N(R 47 )-C(O)-CHR 48 -NR 49 R 50 (In the formula, R 47 is H or CH3, and R 48 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 49 and R 50 each of which is independently H, CH3, or acetyl is selected from the group consisting of:

[0072] In other embodiments, R 3 teeth, (i) C optionally substituted with one or more substituents 6~10 aryl, (ii) a 5- to 10-membered heteroaryl optionally substituted with one or more substituents; (iii)-C 1~6 Alkylene (C 6~10 aryl) (wherein C 6~10 Aryl is optionally substituted with one or more substituents, where C 1~6 alkylene optionally substituted with one or more substituents; (iv)-C 1~6 alkylene(5-10 membered heteroaryl), wherein the 5-10 membered heteroaryl is optionally substituted with one or more substituents, wherein C 1~6 alkylene optionally substituted with one or more substituents; (v)-C 1~6 Alkylene-N(H)C(O)R 28 (In the formula, R 28 is C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, and -NR 29 R 30 wherein C is selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 29 and R 30 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vi)-(C 6~10 (arylene)-C(O)NR 31 R 32 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 31 R 32 (In the formula, R 31 and R 32 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vii)-(C 6~10 Arylene)-NR 33 R 34 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 33 R 34 (In the formula, R 33 and R 34 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 35 , -C(O)NR 36 R 37 , and -SO2R 38 wherein C is independently selected from the group consisting of 1~6Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 35 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents; R 36 and R 37 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 38 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii)-(C 6~10 Arylene)-SO2NR 39 R 40 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 39 R 40 (In the formula, R 39 and R 40 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ix)-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 41 R 42 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 41 R 42 (In the formula, R 41 and R 42 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 43 , and -C(O)NR 44 R 45 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 43 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 44 and R 45 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (x)-(C 6~10 arylene)-OR46 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 46 (In the formula, R 46 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and (xi)-C 1~6 Alkylene-(C 6~10 arylene)-N(R 47 )-C(O)-CHR 48 -N(H)R 50 (In the formula, R 47 is H or CH3, and R 48 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 50 is H, CH3 or acetyl) is selected from the group consisting of:

[0073] In some embodiments, R 3 is C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, where —C 1~6 Alkylene (C 6~10 aryl) and -C 1~6Alkylene (5-10 membered heteroaryl) C 1~6 An alkylene is optionally substituted with one or more substituents.

[0074] In some embodiments, R 3 is C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene (5- to 10-membered heteroaryl) is halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207(In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0075] In some embodiments, R 3 is C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is selected from halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, and C 6~10 Optionally substituted with one or more substituents each independently selected from the group consisting of aryl.

[0076] In some embodiments, R 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 1~3 Alkylene is C 6~10 aryl. In some embodiments, R 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0077] In some embodiments, R 3 -C 1~2 Alkylene (C 6~10 aryl) and -C 1~2 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein -C 1~2 Alkylene (C 6~10 aryl) and -C 1~2 Alkylene (5-10 membered heteroaryl) C 1~2 Alkylene is a group that can be substituted with halogen, hydroxy, -NO2, C 1~6 Alkoxy, and C 6~10 Optionally substituted with one or more substituents each independently selected from the group consisting of aryl.

[0078] In other embodiments, R 3 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 1~2 Alkylene is a group that can be substituted with halogen, hydroxy, -NO2, C1~6 Alkoxy, and C 6~10 Optionally substituted with one or more substituents each independently selected from the group consisting of aryl.

[0079] In some embodiments, R 3 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 Aryl is a group containing halogen, hydroxyl, -NO2, and C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 3 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 The aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxy, and —NO. In some embodiments, R 3 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 The aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen and hydroxy. In some embodiments, R 3 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 The aryl is optionally substituted with hydroxy.

[0080] In some embodiments, R 3 is -CH2-phenyl or -CH2-naphthyl, where phenyl or naphthyl is selected from halogen, hydroxy, -NO2, and C 1~6 In other embodiments, R is optionally substituted with one or two substituents each independently selected from the group consisting of alkoxy. 3is —CH-phenyl or —CH-naphthyl, where phenyl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxyl, and —NO. In some embodiments, R 3 is —CH-phenyl or —CH-naphthyl, where phenyl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen and hydroxyl. In some embodiments, R 3 is —CH 2 -phenyl or —CH 2 -naphthyl, where the phenyl is optionally substituted with hydroxyl.

[0081] In some embodiments, R 3 is -CH2-phenyl, where phenyl is substituted with halogen, hydroxy, -NO2, and C 1~6 In some embodiments, R is optionally substituted with one or two substituents each independently selected from the group consisting of alkoxy. 3 is -CH-phenyl, where phenyl is optionally substituted with one or two substituents each independently selected from the group consisting of halogen, hydroxy, and -NO. In some embodiments, R 3 is —CH-phenyl, where phenyl is unsubstituted. In some embodiments, R 3 is -CH2-phenyl, where phenyl is substituted with halogen, hydroxy, -NO2, and C 1~6 In some embodiments, R is substituted with one or two substituents each independently selected from the group consisting of alkoxy. 3 is -CH-phenyl, where phenyl is substituted with one or two substituents each independently selected from the group consisting of halogen, hydroxy, and -NO. In some embodiments, R 3 is —CH 2 -phenyl, wherein the phenyl is substituted with one or two substituents each independently selected from the group consisting of halogen and hydroxy.

[0082] In some embodiments, R 3is —CH-phenyl, where phenyl is substituted with one or two substituents each independently selected from the group consisting of —F, —Cl, —Br, and —I. In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -F. In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -Cl. In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -Br. In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -I. In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one substituent that is -F. In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one substituent that is -Cl. In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one substituent that is -Br. In some embodiments, R 3 is -CH2-phenyl, where the phenyl is substituted with one substituent which is -I.

[0083] In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is hydroxy. In some embodiments, R 3 is -CH-phenyl, where phenyl is substituted with one substituent that is hydroxy. In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -NO. In some embodiments, R 3 is -CH-phenyl, where the phenyl is substituted with one substituent that is -NO. In some embodiments, R3 is —CH2-phenyl, where each phenyl is independently C 1~6 In some embodiments, R is substituted with one or two substituents that are alkoxy. 3 is —CH2-phenyl, where each phenyl is independently C 1~3 In some embodiments, R is substituted with one or two substituents that are alkoxy. 3 is -CH2-phenyl, where the phenyl is substituted with one substituent which is methoxy.

[0084] In some embodiments, R 3 teeth [ka] where R 89 is H, halogen, hydroxyl or C 1~3 In some embodiments, R 89 is H, halogen, or hydroxyl. In some embodiments, R 89 is H, Cl, or hydroxyl. In some embodiments, R 89 is Cl or hydroxyl. In some embodiments, R 89 is hydroxyl.

[0085] In some embodiments, R 3 -C 1~2 Alkylene (C 10 aryl), where C 10 Aryl is substituted with halogen, hydroxyl and -NO2, as well as C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 3 is -CH2-naphthyl.

[0086] In some embodiments, R 3 -C 1~2alkylene(6-membered heteroaryl), where the 6-membered heteroaryl is selected from halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0087] In some embodiments, R 3 is selected from the group consisting of -CH-pyridinyl, -CH-indolyl, -CH-thiophenyl, -CH-thiazolyl, -CH-furanyl, -CH-benzothiophenyl, and -CH-imidazolyl. 3 is -CH-pyridinyl. In some embodiments, R 3 is -CH-indolyl. In some embodiments, R 3 is -CH-thiophenyl. In some embodiments, R 3 is -CH-thiazolyl. In some embodiments, R 3 is -CH-furanyl. In some embodiments, R 3 is —CH-benzothiophenyl. In some embodiments, R 3 is -CH2-imidazolyl.

[0088] In some embodiments, R 3 -C 1~2 Alkylene (C6 aryl) and -C 1~2 In other embodiments, R is selected from the group consisting of alkylene (6-membered heteroaryl), where C aryl and 6-membered heteroaryl are optionally substituted with hydroxyl. 3 is -CH2-phenyl or -CH2-pyridinyl, where the phenyl is optionally substituted with hydroxyl.

[0089] R 4 Embodiments of the present invention In some embodiments, R 4 teeth, (I C 1~6 Alkylene-N(R 53 )C(O)NR 51 R52 (In the formula, R 51 and R 52 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 53 is H or C 1~6 alkyl), (ii)-C 1~6 Alkylene-N(R 55 )C(O)R 54 (In the formula, R 54 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 55 is H or C 1~6 alkyl), (iii)-(C 6~10 (arylene)-C(O)NR 56 R 57 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 56 R 57 (In the formula, R 56 and R 57 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (iv)-(C 6~10 arylene)-N(R 59 )C(O)R 58or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 59 )C(O)R 58 (In the formula, R 58 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents, where R 59 is H or C 1~6 alkyl), (v)-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 (In the formula, R 60 and R 61 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 62 is H or C 1~6 alkyl), (vi)-(C 6~10 arylene)-N(R 64 )SO2R 63 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 64 )SO2R 63 (In the formula, R 63 is C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 64 is H or C 1~6 alkyl), (vii)-(C 6~10 Arylene)-SO2NR 65 R 66 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 65 R 66 (In the formula, R 65 and R 66 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii)-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 (In the formula, R 67 and R 68 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 69 , and -C(O)NR 70 R 71 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 69 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 70 and R 71 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ix)-(C 6~10 Arylene)-NR 72 R 73 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 72 R 73 (In the formula, R 72 and R 73 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (x)-(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 (In the formula, R 74 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (xi)-C 1~6 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -NR 77 R 78 (In the formula, R 75 is H or CH3, and R 76 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 77 and R 78 each of which is independently H, CH, or acetyl, and (xii)-C 1~6 Alkylene-(C 6~10 Arylene)-CN is selected from the group consisting of:

[0090] In some embodiments, R 4 teeth, (I C 1~6 Alkylene-N(R 53 )C(O)NR 51 R 52 (In the formula, R 51 and R 52 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 53 is H or C 1~6 alkyl), (ii)-C 1~6 Alkylene-N(R 55 )C(O)R 54 (In the formula, R54 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 55 is H or C 1~6 alkyl), (iii)-(C 6~10 (arylene)-C(O)NR 56 R 57 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 56 R 57 (In the formula, R 56 and R 57 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (iv)-(C 6~10 arylene)-N(R 59 )C(O)R 58 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 59 )C(O)R 58 (In the formula, R 58 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents, where R 59 is H or C 1~6 alkyl), (v)-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 (In the formula, R 60 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 61 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 60 or R 61 C 1~6 Alkyl is optionally substituted with one or more substituents, where R 60 or R 61 C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 62 is H or C 1~6 alkyl), (vi)-(C 6~10 arylene)-N(R 64 )SO2R 63 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 64 )SO2R 63 (In the formula, R 63 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 64 is H or C 1~6 alkyl), (vii)-(C 6~10 Arylene)-SO2NR 65 R66 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 65 R 66 (In the formula, R 65 and R 66 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii)-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 (In the formula, R 67 and R 68 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 69 , and -C(O)NR 70 R 71 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 69 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 70 and R 71Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ix)-(C 6~10 Arylene)-NR 72 R 73 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 72 R 73 (In the formula, R 72 and R 73 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (x)-(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 (In the formula, R 74 is C 2~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 2~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (xi)-C 1~6 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -NR 77 R 78 (In the formula, R 75 is H or CH3, and R 76is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 77 and R 78 each of which is independently H, CH, or acetyl, and (xii)-C 1~6 Alkylene-(C 6~10 Arylene)-CN is selected from the group consisting of:

[0091] In other embodiments, R 4 teeth, (I C 1~6 Alkylene-N(H)C(O)NR 51 R 52 (In the formula, R 51 and R 52 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ii)-C 1~6 Alkylene-N(H)C(O)NR 54 (In the formula, R 54 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (iii)-(C 6~10 (arylene)-C(O)NR 56 R 57 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 56 R 57(In the formula, R 56 and R 57 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (iv)-(C 6~10 Arylene)-N(H)C(O)R 58 or -C 1~6 Alkylene-(C 6~10 Arylene)-N(H)C(O)R 58 (In the formula, R 58 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents; (v)-(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 (In the formula, R 60 and R 61 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vi)-(C 6~10 Arylene)-N(H)SO2R 63 or -C 1~6Alkylene-(C 6~10 Arylene)-N(H)SO2R 63 (In the formula, R 63 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (vii)-(C 6~10 Arylene)-SO2NR 65 R 66 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 65 R 66 (In the formula, R 65 and R 66 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (viii)-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 (In the formula, R 67 and R 68 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 69 , and -C(O)NR 70 R 71 wherein C is independently selected from the group consisting of 1~6Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 69 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 70 and R 71 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (ix)-(C 6~10 Arylene)-NR 72 R 73 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 72 R 73 (In the formula, R 72 and R 73 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (x)-(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 (In the formula, R 74 is H, C 1~6 Alkyl, C6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; (xi)-C 1~6 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 (In the formula, R 75 is H or CH3, and R 76 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 78 is H, CH3 or acetyl), and (xii)-C 1~6 Alkylene-(C 6~10 Arylene)-CN is selected from the group consisting of:

[0092] In some embodiments, R 4 -C 1~6 Alkylene-N(R 53 )C(O)NR 51 R 52 where R 51 and R 52 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 53 is H or alkyl.

[0093] In other embodiments, R 4 -C 1~6Alkylene-N(R 53 )C(O)NR 51 R 52 where R 51 and R 52 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl), where R 53 is H or C 1~6 It is alkyl.

[0094] In some embodiments, R 4 -C 1~6 Alkylene-N(H)C(O)NR 51 R 52 where R 51 and R 52 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0095] In other embodiments, R 4 -C 1~6 Alkylene-N(H)C(O)NR 51 R 52 where R 51 and R 52 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkyl. 4 -C 3~4 Alkylene-N(H)C(O)NR 51 R 52 and R 51 and R 52 Each of is H.

[0096] In some embodiments, R 4 teeth [ka] where R 90 and R 91 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 2 is 1, 2, 3, or 4. In some embodiments, R 90 and R91 Each of is H. In some embodiments, n 2 is 3 or 4. In some embodiments, n 2 is 3. In other embodiments, n 2 is 4.

[0097] In some embodiments, R 4 teeth [ka] where R 92 and R 93 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 6- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 6-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 92 and R 93 Each of is H.

[0098] In some embodiments, R 4 teeth [ka] where R 94 and R 95 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 6- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10Aryl and 6-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 In other embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 94 and R 95 Each of is H.

[0099] In some embodiments, R 4 -C 1~6 Alkylene-N(R 55 )C(O)R 54 where R 54 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 55 is H or C 1~6 It is alkyl.

[0100] In other embodiments, R 4 -C 1~6 Alkylene-N(R 55 )C(O)R 54 where R 54 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl), where R 55 is H or C 1~6 It is alkyl.

[0101] In some embodiments, R 4 -C 1~6 Alkylene-NHC(O)R 54 where R 54 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0102] In other embodiments, R 4 -C 1~6 Alkylene-NHC(O)R 54 where R 54 is C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0103] In some embodiments, R 4 -C 3~4 Alkylene-NHC(O)R 54 and R 54 is halogen, hydroxy, -NO2, and C 1~6and 5-10 membered heteroaryl optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0104] In other embodiments, R 4 -C 3~4 Alkylene-NHC(O)R 54 and R 54 is halogen, hydroxy, -NO2, and C 1~6 and pyridinyl optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0105] In some embodiments, R 4 teeth [ka] where R 96 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 3 is 1, 2, 3, or 4. In some embodiments, R 96 is pyridinyl. In some embodiments, n 3 is 3 or 4. In some embodiments, n 3 is 3. In other embodiments, n 3 is 4.

[0106] In some embodiments, R 4 teeth [ka] where R 97 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 97 is a C6 aryl or a 5- to 6-membered heteroaryl.

[0107] In some embodiments, R 4 teeth [ka] where R 98 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 98 is a C6 aryl or a 5- to 6-membered heteroaryl.

[0108] In some embodiments, R 4 is -(C 6~10 (arylene)-C(O)NR 56 R 57 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR56 R 57 where R 56 and R 57 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0109] In other embodiments, R 4 is -(C 6~10 (arylene)-C(O)NR 56 R 57 or -C 1~6 Alkylene-(C 6~10 (arylene)-C(O)NR 56 R 57 where R 56 and R 57 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203(In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkyl. 4 -C 1~2 Alkylene-(C6 arylene)-C(O)NR 56 R 57 and R 56 and R 57 Each of is H.

[0110] In some embodiments, R 4 teeth [ka] where R 99 and R 100 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 4 is 0, 1, 2, 3, or 4. In other embodiments, R 99 and R 100 Each of these is H, C1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl. In some embodiments, R 99 and R 100 Each of H and C 1~6 In some embodiments, R 99 and R 100 Each of is H. In some embodiments, n 4 is 1 or 2. In some embodiments, n 4 is 1. In other embodiments, n 4 is 2.

[0111] In some embodiments, R 4 teeth [ka] where R 101 and R 102 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 In other embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 101 and R 102 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl. In some embodiments, R 101 and R 102 Each of H and C 1~6 In some embodiments, R 101 and R 102Each of is H.

[0112] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 59 )C(O)R 58 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 59 )C(O)R 58 where R 58 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents, where R 59 is H or C 1~6 It is alkyl.

[0113] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 59 )C(O)R 58 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 59 )C(O)R 58 where R 58 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are substituted with halogen, —OH, —NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl), where R 59 is H or C 1~6 It is alkyl.

[0114] In some embodiments, R 4 is -(C 6~10 Arylene)-N(H)C(O)R 58 or -C 1~6 Alkylene-(C 6~10 Arylene)-N(H)C(O)R 58 where R 58 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents.

[0115] In some embodiments, R 4 is -(C 6~10 Arylene)-N(H)C(O)R 58 or -C 1~6 Alkylene-(C 6~10 Arylene)-N(H)C(O)R 58 where R 58 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207(In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are substituted with halogen, —OH, —NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0116] In some embodiments, R 4 is -C1 alkylene-(C6 arylene)-N(H)C(O)R 58 and R 58 is C 1~6 Alkyl, C 6~10 In some embodiments, R is selected from the group consisting of aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl. 4 is -C1 alkylene-(C6 arylene)-N(H)C(O)R 58 and R 58 is C 6~10 In some embodiments, R is selected from the group consisting of aryl and 5-10 membered heterocycloalkyl. 4 is -C1 alkylene-(C6 arylene)-N(H)C(O)R 58 and R 58 is selected from the group consisting of C6 aryl, 5- to 6-membered heteroaryl, and 5- to 6-membered heterocycloalkyl. 4 is -C1 alkylene-(C6 arylene)-N(H)C(O)R 58 and R 58 is pyrrolidinyl. In other embodiments, R 4 is -C1 alkylene-(C6 arylene)-N(H)C(O)R 58 and R 58 is phenyl.

[0117] In some embodiments, R 4 teeth [ka] where R 103 is C 1~6 Alkyl, C 6~10aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is a group that can be substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are substituted with halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 5 is 0, 1, 2, 3, or 4.

[0118] In some embodiments, R 4 teeth [ka] wherein X 1 CH, CR 104 , or N and X 2 CH, CR 105 , or N and X 3 CH, CR 106 , or N and X 4 CH, CR 107 , or N and X 5 CH, CR 108 , or N and R 104 , R 105 , R 106 , R 107 , and R 108 Each of the groups is selected from halogen, hydroxy, -NO2, and C 1~6 alkoxy is independently selected from the group consisting of:

[0119] In some embodiments, R 4 teeth [ka] where R 109 is H, halogen, hydroxy, -NO2, and C 1~6In other embodiments, R 109 is H.

[0120] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 where R 60 and R 61 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 62 is H or C 1~6 It is alkyl.

[0121] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 where R 60 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 61 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 60 or R 61 C 1~6Alkyl is optionally substituted with one or more substituents, where R 60 or R 61 C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 62 is H or C 1~6 It is alkyl.

[0122] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 where R 60 and R 61 Each of the 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 62 is H or C 1~6 It is alkyl.

[0123] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 where R 60 and R 61 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl), where R 62 is H or C 1~6 It is alkyl.

[0124] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C6~10 arylene)-N(R 62 )C(O)NR 60 R 61 where R 60 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 61 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 60 or R 61 C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl), where R 60 or R 61 C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C1~6 alkyl, and R 209 is C 1~6 alkyl), where R 62 is H or C 1~6 It is alkyl.

[0125] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 62 )C(O)NR 60 R 61 where R 60 and R 61 Each of the 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl), where R 62 is H or C 1~6 It is alkyl.

[0126] In some embodiments, R 4 is -(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 where R 60 and R 61 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0127] In some embodiments, R 4 is -(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 where R 60 is H, C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl; R 61 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 60 or R 61 C 1~6 Alkyl is optionally substituted with one or more substituents, where R 60 or R 61 C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0128] In some embodiments, R 4 is -(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 where R 60 and R 61 Each of the 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0129] In some embodiments, R 4 is -(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 where R 60 and R 61 Each of these is H, C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0130] In some embodiments, R 4 is -(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 (arylene)-N(H)C(O)NR60 R 61 where R 60 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 61 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 60 or R 61 C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl), where R 60 or R 61 C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0131] In some embodiments, R 4 is -(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 or -C 1~6 Alkylene-(C 6~10 (arylene)-N(H)C(O)NR 60 R 61 where R 60 and R 61 Each of the 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0132] In some embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-N(H)C(O)NR 60 R 61 where R 60 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 61 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl. In some embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-N(H)C(O)NR 60 R 61 and R 60 is H and R 61 is phenyl.

[0133] In some embodiments, R 4 teeth [ka] where R 110 and R 111 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 6 is 0, 1, 2, 3, or 4.

[0134] In some embodiments, R 4 teeth [ka] where R 110 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 111 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 6 is 0, 1, 2, 3, or 4. In some embodiments, R 110 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 111 is C 1~6 Alkyl, C 6~10 It is selected from the group consisting of aryl, and 5- to 10-membered heteroaryl.

[0135] In some embodiments, R 4 teeth [ka] where R 110and R 111 Each of the 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 6 is 0, 1, 2, 3, or 4.

[0136] In some embodiments, R 4 teeth [ka] where R 112 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 7 is 0, 1, 2, 3, or 4.

[0137] In some embodiments, R 4 teeth [ka] where R 112 is C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 7 is 0, 1, 2, 3, or 4. In some embodiments, R 112 is C 1~6 Alkyl, C 6~10 It is selected from the group consisting of aryl, and 5- to 10-membered heteroaryl.

[0138] In some embodiments, R 4 teeth [ka] wherein X 6 CH, CR 113 or N and X 7 CH, CR 114 or N and X 8 CH, CR 115 or N and X 9 CH, CR 116 or N and X 10 CH, CR 117 or N, and each R 113 , R 114 , R 115 , R 116 , and R 117 is halogen, hydroxy, -NO2, and C 1~6 alkoxy is independently selected from the group consisting of:

[0139] In some embodiments, R 4 teeth [ka] where R 118is H, halogen, hydroxy, -NO2, and C 1~6 In other embodiments, R 118 is H.

[0140] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 64 )SO2R 63 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 64 )SO2R 63 where R 63 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 Aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R 64 is H or C 1~6 It is alkyl.

[0141] In some embodiments, R 4 is -(C 6~10 arylene)-N(R 64 )SO2R 63 or -C 1~6 Alkylene-(C 6~10 arylene)-N(R 64 )SO2R 63 where R 63 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200(In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl), where R 64 is H or C 1~6 It is alkyl.

[0142] In some embodiments, R 4 is -(C 6~10 Arylene)-N(H)SO2R 63 or -C 1~6 Alkylene-(C 6~10 Arylene)-N(H)SO2R 63 where R 63 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0143] In some embodiments, R 4 is -(C 6~10 Arylene)-N(H)SO2R 63 or -C 1~6 Alkylene-(C 6~10 Arylene)-N(H)SO2R 63 where R 63 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0144] In some embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-N(H)SO2R 63 and R 63 is halogen, hydroxy, -NO2, and C 1~6 In other embodiments, R is a C aryl optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 4 -C 1~2 Alkylene-(C6 arylene)-N(H)SO2R 63 and R 63 is phenyl. In some embodiments, R 4 is -C1 alkylene-(C6 arylene)-N(H)SO2R 63 and R 63 is phenyl.

[0145] In some embodiments, R 4 teeth [ka] where R 119 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a group that can be substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 8 is 0, 1, 2, 3, or 4. In other embodiments, R 119 is C1~6 Alkyl, C 6~10 It is selected from the group consisting of aryl, and 5- to 10-membered heteroaryl.

[0146] In some embodiments, R 4 teeth [ka] wherein X 11 CH, CR 120 or N and X 12 CH, CR 121 or N and X 13 CH, CR 122 or N and X 14 CH, CR 123 or N and X 15 CH, CR 124 or N and R 120 , R 121 , R 122 , R 123 and R 124 Each of the groups is selected from halogen, hydroxy, -NO2, and C 1~6 alkoxy is independently selected from the group consisting of:

[0147] In some embodiments, R 4 teeth [ka] where R 125 is H, halogen, hydroxy, -NO2, and C 1~6 In some embodiments, R is selected from the group consisting of alkoxy. 125 is H.

[0148] In some embodiments, R 4 is -(C 6~10 Arylene)-SO2NR 65 R 66 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 65 R 66 where R65 and R 66 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0149] In some embodiments, R 4 is -(C 6~10 Arylene)-SO2NR 65 R 66 or -C 1~6 Alkylene-(C 6~10 Arylene)-SO2NR 65 R 66 where R 65 and R 66 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0150] In some embodiments, R 4 teeth [ka] where R 126 and R 127 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 9 is 0, 1, 2, 3, or 4. In some embodiments, R 126 and R 127 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl.

[0151] In some embodiments, R 4 teeth [ka] wherein X 16 CH, CR 128 or N and X 17 CH, CR 129 or N and X 18 CH, CR 130 or N and X 19 CH, CR 131 or N and X 20 CH, CR 132 or N and R 128 , R 129 , R 130 , R 131 and R 132 Each of the halogens -OH, -NO2, and C 1~6 alkoxy is independently selected from the group consisting of:

[0152] In some embodiments, R 4 teeth [ka] where R 133 H, halogens, -OH, -NO2, and C 1~6 In other embodiments, R 133 is H.

[0153] In some embodiments, R 4 is -(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 where: R 67 and R 68 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 69 , and -C(O)NR70 R 71 wherein C is independently selected from the group consisting of 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 69 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R 70 and R 71 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0154] In some embodiments, R 4 is -(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 where: R 67 and R 68 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 69 , and -C(O)NR 70 R 71 wherein C is independently selected from the group consisting of 1~6Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: R 69 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: R 70 and R 71 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0155] In some embodiments, R 4 is -(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 or -C 1~6 Alkylene-(C 6~10 arylene)-(C 1~6 (Alkylene)-NR 67 R 68 where: R 67 and R 68 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 69 , and -C(O)NR 70 R 71 wherein C is independently selected from the group consisting of1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 69 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 70 and R 71 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0156] In some embodiments, R 4 is -C1 alkylene-(C6 arylene)-(C1 alkylene)-NR 67 R 68 and R 67 and R 68 Each of R is H. In other embodiments, R4 is -C1 alkylene-(C6 arylene)-(C1 alkylene)-NR 67 R 68 and R 67 is H and R 68 HA-C(O)R 69 and R 69 is C alkyl. In some embodiments, R 4 is -C1 alkylene-(C6 arylene)-(C1 alkylene)-NR 67 R 68 and R 67 is H and R 68 is -C(O)NR 70 R 71 and R 70 and R 71 Each of is H.

[0157] In some embodiments, R 4 teeth [ka] where R 134 and R 135 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 136 , and -C(O)NR 137 R 138 wherein C is independently selected from the group consisting of 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 10 is 0, 1, 2, 3, or 4, where n 11 is 0, 1, 2, 3, or 4, R 136 is C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 137 and R 138 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0158] In some embodiments, R 4 teeth [ka] where: R 139 and R 140 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 141 , and -C(O)NR 142 R 143 wherein C is independently selected from the group consisting of 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 141 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 142 and R 143 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 139 and R 140 Each of the groups is H, -C(O)R 141 , and -C(O)NR 142 R 143 where R is independently selected from the group consisting of 141 is C 1~6 alkyl, and R 142 and R 143 Each of is H.

[0159] In some embodiments, R 4 is -(C 6~10Arylene)-NR 72 R 73 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 72 R 73 where R 72 and R 73 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0160] In some embodiments, R 4 is -(C 6~10 Arylene)-NR 72 R 73 or -C 1~6 Alkylene-(C 6~10 Arylene)-NR 72 R 73 where R 72 and R 73 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201(In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0161] In some embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-NR 72 R 73 and R 72 and R 73 Each of H and C 1~6 alkyl, wherein C 1~6 Alkyl is 5-10 membered heterocycloalkyl, halogen, hydroxy, -NO2, and C 1~6 In other embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 4 -C 1~2 Alkylene-(C6 arylene)-NR 72 R 73 and R 72 is H and R 73 is a 5- to 10-membered heterocycloalkyl, halogen, hydroxy, -NO2, and C 1~6 C optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy 1~6 In some embodiments, R 4 -C1~2 Alkylene-(C6 arylene)-NR 72 R 73 and R 72 is H and R 73 is a C alkyl substituted with morpholinyl. In some embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-NR 72 R 73 and R 72 is H and R 73 is C 1~6 In other embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-NR 72 R 73 and R 72 is H and R 73 is a C5 alkyl.

[0162] In some embodiments, R 4 teeth [ka] where R 144 and R 145 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, where n 12 is 0, 1, 2, 3, or 4. In some embodiments, n 12 is 1 or 2. In other embodiments, n 12 is 1. In other embodiments, R144 is H and R 145 are halogens, -OH, -NO2, C 1~6 C optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl 1~6 In some embodiments, R 144 is H and R 145 is a C alkyl substituted with morpholinyl. In other embodiments, R 144 is H and R 145 is C 1~6 In other embodiments, R 144 is H and R 145 is a C5 alkyl.

[0163] In some embodiments, R 4 is -(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 where R 74 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents. 4 is -(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 where R 74 is C 2~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 2~6 Alkyl is optionally substituted with one or more substituents, where C 6~10The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents. In some embodiments, R 4 is -(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 where R 74 is C 3~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 3~6 Alkyl is optionally substituted with one or more substituents, where C 6~10 The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

[0164] In some embodiments, R 4 is -(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 where R 74 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0165] In some embodiments, R 4 is -(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR 74 where R 74 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 In other embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl. 4 is -(C 6~10 arylene)-OR 74 or -C 1~6 Alkylene-(C 6~10 arylene)-OR74 where R 74 is C 2~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 2~6 Alkyl is a halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl.

[0166] In some embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-OR 74 and R 74 is a 5- to 10-membered heterocycloalkyl, halogen, hydroxy, -NO2, and C 1~6 C optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy 1~6 In some embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-OR 74 and R 74 is a 5- to 10-membered heterocycloalkyl, halogen, hydroxy, -NO2, and C 1~6 C optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy 2~6 In some embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-OR 74 and R 74 is C 2~6 In other embodiments, R 4 -C 1~2 Alkylene-(C6 arylene)-OR 74 and R 74is a C2 alkyl substituted with morpholinyl.

[0167] In some embodiments, R 4 teeth [ka] where R 146 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, where n 13 is 0, 1, 2, 3, or 4. In some embodiments, n 13 is 1 or 2. In other embodiments, n 13 is 1. In some embodiments, R 146 is C 2~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 In other embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl. 146 is C 2~6 Alkyl, C 6~10It is selected from the group consisting of aryl, and 5- to 10-membered heteroaryl.

[0168] In some embodiments, R 4 teeth [ka] where R 147 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 In other embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl. 147 is C 2~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 2~6 Alkyl is a halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl. 147 is C 2~6 Alkyl, C 6~10 In other embodiments, R 147 are halogens, -OH, -NO2, C 1~6C optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl 2~6 In some embodiments, R 147 is a C alkyl substituted with morpholinyl. In other embodiments, R 147 is a C2 alkyl.

[0169] In some embodiments, R 4 -C 1~6 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -NR 77 R 78 where R 75 is H or CH3, and R 76 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 77 and R 78 Each of is independently H, CH3, or acetyl.

[0170] In some embodiments, R 4 -C 1~6 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 where R 75 is H or CH3, and R 76 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 78 is H, CH3 or acetyl.

[0171] In some embodiments, R 4 -C 1~2 Alkylene-(C6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 and R 75 is H and R 76 is H and R 78 is H or acetyl. In other embodiments, R 4 -C 1~2 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 and R 75 is H and R 76 is H and R 78 is H. In some embodiments, R 4 -C 1~2 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 and R 75 is H and R 76 is H and R 78 is acetyl.

[0172] In some embodiments, R 4 -C 1~2 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 and R 75 is H and R 76 is a C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 78 is H.

[0173] In some embodiments, R 4 -C 1~2 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR76 -N(H)R 78 and R 75 is H and R 76 is a hydroxyl-substituted C 1~6 alkyl, and R 78 is H. In some embodiments, R 4 -C 1~2 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 and R 75 is H and R 76 C is substituted with -COOH 1~6 alkyl, and R 78 is H. In some embodiments, R 4 -C 1~2 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 and R 75 is H and R 76 is C substituted with -NH2 1~6 alkyl, and R 78 is H. In some embodiments, R 4 -C 1~2 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 and R 75 is H and R 76 is C substituted with -C(O)NH2 1~6 alkyl, and R 78 is H. In some embodiments, R 4 -C 1~2 Alkylene-(C 6~10 arylene)-N(R 75 )-C(O)-CHR 76 -N(H)R 78 and R 75 is H and R 76 is C substituted with -N(H)C(O)NH2 1~6 alkyl, and R78 is H.

[0174] In some embodiments, R 4 teeth [ka] where R 148 is H or CH3, and R 149 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 150 is H, CH3 or acetyl, where n 14 is 0, 1, 2, 3, or 4. In other embodiments, n 14 is 1 or 2. In some embodiments, n 14 is 1. In some embodiments, R 148 is H and R 149 is H and R 150 is H or acetyl. In other embodiments, R 148 is H and R 149 is H and R 150 is H. In some embodiments, R 148 is H and R 149 is H and R 150 is acetyl. In some embodiments, R 148 is H and R 149 is a C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 150 is H. In some embodiments, R 148 is H and R 149 is a hydroxyl-substituted C 1~6 alkyl, and R 150 is H. In some embodiments, R 148 is H and R 149 C is substituted with -COOH1~6 alkyl, and R 150 is H. In some embodiments, R 148 is H and R 149 is C substituted with -NH2 1~6 alkyl, and R 150 is H. In some embodiments, R 148 is H and R 149 is C substituted with -C(O)NH2 1~6 alkyl, and R 150 is H. In some embodiments, R 148 is H and R 149 is C substituted with -N(H)C(O)NH2 1~6 alkyl, and R 150 is H.

[0175] In some embodiments, R 4 -C 1~6 Alkylene-(C 6~10 In other embodiments, R 4 -C 1~2 alkylene-(C6 arylene)-CN. In other embodiments, R 4 is -C alkylene-(C arylene)-CN. In some embodiments, R 4 teeth [ka] where n 15 is 0, 1, 2, 3, or 4. In other embodiments, n 15 is 1 or 2. In some embodiments, R 4 teeth [ka] is.

[0176] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth, [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] In some embodiments, R 4 teeth [ka] is.

[0177] R 5 and n 1 Embodiments of the present invention In some embodiments, R 5 teeth, (i)-NR 79 R 80 (In the formula, R 79 and R 80Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 or R 79 and R 80 together with the N atom to which they are attached form a 5- to 10-membered heteroaryl or a 5- to 10-membered heterocycloalkyl, where C 1~6 alkyl is optionally substituted with one or more substituents, wherein 5- to 10-membered heteroaryl and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents; R 81 is H, -NH2, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 82 , R 83 , and R 84 Each of these is H, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (ii)-N + R 85 R 86 R 87 (In the formula, R 85 , R 86 , and R 87 Each of the is independently C 1~6 alkyl) is selected from the group consisting of:

[0178] In some embodiments, R 5 teeth, (i)-NR 79 R 80 (In the formula, R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R84 or R 79 and R 80 together with the N atom to which they are attached form a 5- to 10-membered heteroaryl or a 5- to 10-membered heterocycloalkyl, where C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6and 5-10 membered heteroaryl and 5-10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —OH, —NO, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: R 81 is H, -NH2, C 1~16 Alkyl, C1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 82 , R 83 , and R 84 Each of these is H, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (ii)-N + R 85 R 86 R 87 (In the formula, R 85 , R 86 , and R 87 Each of the is independently C 1~6 alkyl) is selected from the group consisting of:

[0179] In other embodiments, R 5 is -NR 79 R 80 where: R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 or R 79 and R 80 together with the N atom to which they are attached form a 5- to 10-membered heteroaryl or a 5- to 10-membered heterocycloalkyl, where C 1~6 Alkyl is optionally substituted with one or more substituents, where 5- to 10-membered heteroaryl and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents, R 81 is H, -NH2, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 82 , R 83, and R 84 Each of these is H, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl.

[0180] In other embodiments, R 5 is -NR 79 R 80 where: R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 or R 79 and R 80 together with the N atom to which they are attached form a 5- to 10-membered heteroaryl or a 5- to 10-membered heterocycloalkyl, where C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and 5-10 membered heteroaryl and 5-10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —OH, —NO, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 alkyl), and R 81 is H, -NH2, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 82 , R 83 , and R 84 Each of these is H, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl.

[0181] In other embodiments, R 5 is -NR 79 R 80 where R 79 and R 80 Each of H and C 1~6 alkyl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 In other embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkyl. 5 is -NR 79 R 80 where R 79 and R 80 Each of R is H. In other embodiments, R 5 is -NR 79 R 80 where R 79 and R 80 Each of the is independently C 1~6 In other embodiments, R 5 is -NR 79 R 80 where R 79 and R 80 Each of the is independently C 1~3 In other embodiments, R 5 is -NR 79 R 80 where R 79and R 80 Each of R is CH. 5 is -NR 79 R 80 where R 79 is H and R 80 is C 1~6 In other embodiments, R 5 is -NR 79 R 80 where R 79 is H and R 80 is C 1~3 In other embodiments, R 5 is -NR 79 R 80 where R 79 is H and R 80 is CH3.

[0182] In other embodiments, R 5 is -NR 79 R 80 where R 79 and R 80 each of which is H and -C(O)R 81 where R is independently selected from the group consisting of 81 is H, -NH2, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 In other embodiments, R 5 is -NR 79 R 80 where R 79 and R 80 Each of the groups is H and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 82 , R 83 , and R 84 Each of these is H, C 1~16 Alkyl, C 1~6 Haloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl. In some embodiments, R 5is -NR 79 R 80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of R is H. In other embodiments, R 5 is -NR 79 R 80 and R 79 and R 80 Each of H and C 1~6 In some embodiments, R 5 is -NH, -NHCH, or -N(CH). In other embodiments, R 5 is -NH. In some embodiments, R 5 is -NHCH3. In other embodiments, R 5 is —N(CH). In other embodiments, R 5 is -NR 79 R 80 where R 79 and R 80 together with the N atom to which they are attached form a 5- to 10-membered heteroaryl or a 5- to 10-membered heterocycloalkyl, wherein the 5- to 10-membered heteroaryl and the 5- to 10-membered heterocycloalkyl are selected from the group consisting of halogen, —OH, —NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkyl. 5 -N + R 85 R 86 R 87 where R 85 , R 86 , and R 87 Each of the is independently C 1~6 In other embodiments, R 85 , R 86 , and R 87 Each of the is independently C 1~3 In other embodiments, R 85 , R 86 , and R 87 Each of n is CH. In some embodiments, 1is 1, 2, 3, 4, 5, or 6. In some embodiments, n 1 is 2, 3, 4, 5, or 6. In some embodiments, n 1 is 2, 3, 4, or 5. In some embodiments, n 1 is 3, 4, or 5. In some embodiments, n 1 is 3 or 4. In some embodiments, n 1 is 1. In some embodiments, n 1 is 2. In some embodiments, n 1 is 3. In some embodiments, n 1 is 4. In some embodiments, n 1 is 5. In some embodiments, n 1 is 6.

[0183] R 6 Embodiments of the present invention In some embodiments, R 6 is alkyl optionally substituted with one or more substituents. In other embodiments, R 6 is C optionally substituted with one or more substituents 1~6 In some embodiments, R 6 is halogen, hydroxy, -NO2, and C 1~6 C optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy 1~6 In some embodiments, R 6 is C optionally substituted with hydroxy 1~6 In other embodiments, R 6 is C optionally substituted with hydroxy 1~5 In some embodiments, R 6 is C optionally substituted with hydroxy 1~4 In some embodiments, R 6 is C optionally substituted with hydroxy 1~3 In some embodiments, R 6 is C optionally substituted with hydroxy1~2 In some embodiments, R 6 is selected from the group consisting of -CH2CH2CH2CH3, -CH(CH3)CH2CH3, -CH2CH(CH3)2, -CH2CH2CH3, -CH(CH3)CH2OH, -CH(CH3)2, -C(CH3)3, -CH(CH3)OH, and -CH2CH3. 6 is selected from the group consisting of -CH(CH3)OH, -CH(CH3)2, -C(CH3)3, -CH2OH, and -CH2CH3. In some embodiments, R 6 is selected from the group consisting of -CH(CH3)OH, -CH(CH3)2, -C(CH3)3, and -CH2CH3. In some embodiments, R 6 is —CH(CH)OH. In some embodiments, R 6 is —CH(CH). In some embodiments, R 6 is —C(CH3)3. In some embodiments, R 6 is -CH2CH3. In some embodiments, R 6 is -CH2OH.

[0184] R 8 Embodiments of the present invention In some embodiments, R 8 is C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 1~6 Alkyl, C 6~10 Aryl, -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl, 5- to 10-membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, where —C 1~6 Alkylene (C 6~10 aryl) and -C1~6 Alkylene (5-10 membered heteroaryl) C 1~6 An alkylene is optionally substituted with one or more substituents.

[0185] In some embodiments, R 8 is C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 1~6 Alkyl, C 6~10 Aryl, -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl, 5- to 10-membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene (5- to 10-membered heteroaryl) is halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0186] In some embodiments, R 8 is C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 1~6 Alkyl, C 6~10 Aryl, -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl, 5- to 10-membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is selected from halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, and C 6~10 Optionally substituted with one or more substituents each independently selected from the group consisting of aryl.

[0187] In some embodiments, R 8 is C 6~10 Aryl, 5-10 membered heteroaryl, -C1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, where —C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 An alkylene is optionally substituted with one or more substituents.

[0188] In some embodiments, R 8 is C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene (5- to 10-membered heteroaryl) is halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C1~6 Alkyl or C 6~10 aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -C 1~6 Alkyl, HaloC 1~6 Alkyl, Amino C 1~6 Alkyl, C 6~10 Aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 5~10 Cycloalkyl, azido, -CN, -COR 200 (In the formula, R 200 is C 1~6 Alkyl or C 6~10aryl), -CO2R 201 (In the formula, R 201 is H or C 1~6 alkyl), -CONR 202 R 203 (In the formula, R 202 and R 203 is H or C 1~6 alkyl), -NR 204 COR 205 (In the formula, R 204 is H or C 1~6 alkyl, and R 205 is C 1~6 alkyl), -SO2NR 206 R 207 (In the formula, R 206 and R 207 is H or C 1~6 alkyl), and -NR 208 SO2R 209 (In the formula, R 208 is H or C 1~6 alkyl, and R 209 is C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of: alkyl.

[0189] In some embodiments, R 8 is C 6~10 Aryl, 5-10 membered heteroaryl, -C 1~6 Alkylene (C 6~10 aryl) and -C 1~6 alkylene (5-10 membered heteroaryl), wherein C 6~10 Aryl and -C 1~6 Alkylene (C 6~10 C of aryl) 6~10 Aryl and 5-10 membered heteroaryl and -C 1~6 The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is selected from halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein -C 1~6 Alkylene (C 6~10 aryl) and -C1~6 Alkylene (5-10 membered heteroaryl) C 1~6 Alkylene is a group that contains halogen, -OH, -NO2, C 1~6 Alkoxy, and C 6~10 Optionally substituted with one or more substituents each independently selected from the group consisting of aryl.

[0190] In some embodiments, R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 1~3 Alkylene is C 6~10 aryl. In some embodiments, R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0191] In some embodiments, R 8 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 Aryl is a group containing halogen, hydroxyl, -NO2, and C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 8 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 The aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxy, and —NO. In some embodiments, R 8 -C1~2 Alkylene (C 6~10 aryl), where C 6~10 The aryl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen and hydroxy. In some embodiments, R 8 -C 1~2 Alkylene (C 6~10 aryl), where C 6~10 The aryl is optionally substituted with hydroxy. In other embodiments, R 8 -C 1~2 alkylene(C6 aryl), where C6 aryl is selected from halogen, hydroxyl, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

[0192] In some embodiments, R 8 is -CH2-phenyl or -CH2-naphthyl, where phenyl or naphthyl is selected from halogen, hydroxy, -NO2, and C 1~6 In other embodiments, R is optionally substituted with one or two substituents each independently selected from the group consisting of alkoxy. 8 is —CH-phenyl or —CH-naphthyl, where phenyl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, hydroxyl, and —NO. In some embodiments, R 8 is —CH-phenyl or —CH-naphthyl, where phenyl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen and hydroxyl. In some embodiments, R 8 is —CH 2 -phenyl or —CH 2 -naphthyl, where the phenyl is optionally substituted with hydroxyl.

[0193] In some embodiments, R 8 is -CH2-phenyl, where phenyl is substituted with halogen, hydroxy, -NO2, and C 1~6In some embodiments, R is optionally substituted with one or two substituents each independently selected from the group consisting of alkoxy. 8 is -CH-phenyl, where phenyl is optionally substituted with one or two substituents each independently selected from the group consisting of halogen, hydroxy, and -NO. In some embodiments, R 8 is —CH-phenyl, where phenyl is unsubstituted. In some embodiments, R 8 is -CH2-phenyl, where phenyl is substituted with halogen, hydroxy, -NO2, and C 1~6 In some embodiments, R is substituted with one or two substituents each independently selected from the group consisting of alkoxy. 8 is -CH-phenyl, where phenyl is substituted with one or two substituents each independently selected from the group consisting of halogen, hydroxy, and -NO. In some embodiments, R 8 is —CH 2 -phenyl, wherein the phenyl is substituted with one or two substituents each independently selected from the group consisting of halogen and hydroxy.

[0194] In some embodiments, R 8 is —CH-phenyl, where phenyl is substituted with one or two substituents each independently selected from the group consisting of —F, —Cl, —Br, and —I. In some embodiments, R 8 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -F. In some embodiments, R 8 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -Cl. In some embodiments, R 8 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -Br. In some embodiments, R 8 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -I. In some embodiments, R 8is -CH-phenyl, where the phenyl is substituted with one substituent that is -F. In some embodiments, R 8 is -CH-phenyl, where the phenyl is substituted with one substituent that is -Cl. In some embodiments, R 8 is -CH-phenyl, where the phenyl is substituted with one substituent that is -Br. In some embodiments, R 8 is -CH2-phenyl, where the phenyl is substituted with one substituent which is -I.

[0195] In some embodiments, R 8 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is hydroxy. In some embodiments, R 8 is -CH-phenyl, where phenyl is substituted with one substituent that is hydroxy. In some embodiments, R 8 is -CH-phenyl, where the phenyl is substituted with one or two substituents, each of which is -NO. In some embodiments, R 8 is -CH-phenyl, where the phenyl is substituted with one substituent that is -NO. In some embodiments, R 8 is —CH2-phenyl, where each phenyl is independently C 1~6 In some embodiments, R is substituted with one or two substituents that are alkoxy. 8 is —CH2-phenyl, where each phenyl is independently C 1~3 In some embodiments, R is substituted with one or two substituents that are alkoxy. 8 is -CH2-phenyl, where the phenyl is substituted with one substituent which is methoxy.

[0196] In some embodiments, R 8 teeth [ka] where R 151is H, halogen, hydroxyl or C 1~3 In some embodiments, R 151 is H, halogen, or hydroxyl. In some embodiments, R 151 is H, Cl, or hydroxyl. In some embodiments, R 151 is Cl or hydroxyl. In some embodiments, R 151 is hydroxyl.

[0197] In some embodiments, R 8 -C 1~2 Alkylene (C 10 aryl), where C 10 Aryl is substituted with halogen, hydroxyl and -NO2, as well as C 1~6 In some embodiments, R is optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy. 8 is -CH2-naphthyl.

[0198] In some embodiments, R 8 is selected from the group consisting of -CH-pyridinyl, -CH-indolyl, -CH-thiophenyl, -CH-thiazolyl, -CH-furanyl, -CH-benzothiophenyl, and -CH-imidazolyl. 8 is -CH-pyridinyl. In some embodiments, R 8 is -CH-indolyl. In some embodiments, R 8 is -CH-thiophenyl. In some embodiments, R 8 is -CH-thiazolyl. In some embodiments, R 8 is -CH-furanyl. In some embodiments, R 8 is —CH-benzothiophenyl. In some embodiments, R 8 is -CH2-imidazolyl.

[0199] R 9 , R 10 , R11 , R 12 , R 13 , R 14 and R 15 Embodiments of the present invention In some embodiments, R 9 is H or C 1~6 In other embodiments, R 9 is H or C 1~5 In some embodiments, R 9 is H or C 1~4 In some embodiments, R 9 is H or C 1~3 In other embodiments, R 9 is H or C 1~2 In some embodiments, R 9 is H or CH. In some embodiments, R 9 is H. In other embodiments, R 9 is CH3. In some embodiments, R 10 is H or C 1~6 In other embodiments, R 10 is H or C 1~5 In some embodiments, R 10 is H or C 1~4 In some embodiments, R 10 is H or C 1~3 In other embodiments, R 10 is H or C 1~2 In some embodiments, R 10 is H or CH. In some embodiments, R 10 is H. In other embodiments, R 10 is CH3. In some embodiments, R 11 is H or C 1~6 In other embodiments, R 11 is H or C 1~5 In some embodiments, R 11 is H or C 1~4In some embodiments, R 11 is H or C 1~3 In other embodiments, R 11 is H or C 1~2 In some embodiments, R 11 is H or CH. In some embodiments, R 11 is H. In other embodiments, R 11 is CH3. In some embodiments, R 12 is H or C 1~6 In other embodiments, R 12 is H or C 1~5 In some embodiments, R 12 is H or C 1~4 In some embodiments, R 12 is H or C 1~3 In other embodiments, R 12 is H or C 1~2 In some embodiments, R 12 is H or CH. In some embodiments, R 12 is H. In other embodiments, R 12 is CH3. In some embodiments, R 13 is H or C 1~6 In other embodiments, R 13 is H or C 1~5 In some embodiments, R 13 is H or C 1~4 In some embodiments, R 13 is H or C 1~3 In other embodiments, R 13 is H or C 1~2 In some embodiments, R 13 is H or CH. In some embodiments, R 13 is H. In other embodiments, R 13 is CH3. In some embodiments, R 14 is H or C1~6 In other embodiments, R 14 is H or C 1~5 In some embodiments, R 14 is H or C 1~4 In some embodiments, R 14 is H or C 1~3 In other embodiments, R 14 is H or C 1~2 In some embodiments, R 14 is H or CH. In some embodiments, R 14 is H. In other embodiments, R 14 is CH3. In some embodiments, R 15 is H or C 1~6 In other embodiments, R 15 is H or C 1~5 In some embodiments, R 15 is H or C 1~4 In some embodiments, R 15 is H or C 1~3 In other embodiments, R 15 is H or C 1~2 In some embodiments, R 15 is H or CH. In some embodiments, R 15 is H. In other embodiments, R 15 is CH3. In other embodiments, R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 Each of is independently H or CH. In some embodiments, R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 Each of is H.

[0200] L's embodiment In some embodiments, L is [ka] wherein X is S or O, and [ka] For each L moiety, either of the attachment points may be attached to either of the two carbon atoms on the remainder of the compound of Formula I or II to which L is attached (as presented in Formula I or II above), provided that they are not attached to the same carbon atom. In other words, the L moieties presented herein can be attached to the remainder of the compound of Formula I or II in either orientation. In some embodiments, L is [ka] L may be made using techniques known to those skilled in the art. For example, L may be [ka] In some embodiments, L is a suitable method described in Lin Chen, L., et al., "Disulfide Bond Formation in Peptides," Current Protocols in Protein Science (2001) 18.6.1-18.6.19, John Wiley & Sons, Inc. [ka] L is [ka] If the Lanthionines: Synthesis and Use for the Solid-Phase Synthesis of an Analogue of Nisin Ring C', J.Org.Chem., 2005, 70(7), pp2430-2438, and Dugave, C., et al., “Synthesis of natural and non natural orthogonally protected lanthionines from N-tritylserine and allo-threonine derivatives”,Tetrahedron:Asymmetry,Volume 8,Number 9,8 May 1997, pp. 1453-1465(13). In some embodiments, L is [ka] L is [ka]

[0039] In some embodiments, L is [ka] In some embodiments, L is [ka] L is [ka] In some embodiments, L is a methyl group, and in some embodiments, L is a methyl group. ... [ka] wherein X is S or O. In some embodiments, L is [ka] wherein X is S. In some embodiments, L is [ka] wherein X is O. In some embodiments, L is [ka] L is [ka] If so, a suitable method is described in Holland-Nell, K., et al., "Maintaining Biological Activity by Using Triazoles as Disufide Bond Mimetics", Angewandte Chemie Int Ed 2011, 50, 5204-5206.

[0201] Embodiments of Chiral Centers *1, *2, *3, *4, *5, *6, *7, and *8 In some embodiments, chiral center *1 is in the S or R configuration. In some embodiments, chiral center *1 is in the S configuration. In some embodiments, chiral center *1 is in the R configuration. In some embodiments, chiral center *2 is in the S or R configuration. In some embodiments, chiral center *2 is in the S configuration. In some embodiments, chiral center *2 is in the R configuration. In some embodiments, chiral center *3 is in the S or R configuration. In some embodiments, chiral center *3 is in the S configuration. In some embodiments, chiral center *3 is in the R configuration. In some embodiments, chiral center *4 is in the S or R configuration. In some embodiments, chiral center *4 is in the S configuration. In some embodiments, chiral center *4 is in the R configuration. In some embodiments, chiral center *5 is in the S or R configuration. In some embodiments, chiral center *5 is in the S configuration. In some embodiments, chiral center *5 is in the R configuration. In some embodiments, chiral center *6 is in the S or R configuration. In some embodiments, chiral center *6 is in the S configuration. In some embodiments, chiral center *6 is in the R configuration. In some embodiments, chiral center *7 is in the S or R configuration. In some embodiments, chiral center *7 is in the S configuration. In some embodiments, chiral center *7 is in the R configuration. In some embodiments, chiral center *8 is in the S or R configuration. In some embodiments, chiral center *8 is in the S configuration. In some embodiments, chiral center *8 is in the R configuration. In some embodiments, chiral center *1 is in the S or R configuration, chiral center *2 is in the S or R configuration, chiral center *3 is in the S or R configuration, chiral center *4 is in the S or R configuration, chiral center *5 is in the S or R configuration, chiral center *6 is in the S or R configuration, chiral center *7 is in the S or R configuration, and chiral center *8 is in the S or R configuration.In some embodiments, chiral center *1 is in the S or R configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S or R configuration, chiral center *4 is in the S or R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S or R configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the S or R configuration. In some embodiments, chiral center *1 is in the S or R configuration, chiral center *2 is in the S or R configuration, chiral center *3 is in the S or R configuration, chiral center *4 is in the S or R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S or R configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the S or R configuration. In some embodiments, chiral center *1 is in the S configuration, chiral center *2 is in the S or R configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S or R configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration. In some embodiments, chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration. In some embodiments, chiral center *1 is in the S configuration, chiral center *2 is in the R configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration. In some embodiments, chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the R configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.In some embodiments, chiral center *1 is in the S configuration, chiral center *2 is in the R configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the R configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0202] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NHR 16 where R 16 is H or C 1~6 alkyl, and R N are (i) H, (ii) C 1~6 alkyl, (iii) -C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) —C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v) -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi) -C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii) —C(O)C 1~3 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) —C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and R 1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 4 teeth, [ka] (In the formula, R 90 and R 91 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 2 is 3 or 4), [ka] (In the formula, R 96 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 3 is 3 or 4), (iii) [ka] (In the formula, R 99 and R 100 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 4 is 1 or 2), [ka] (In the formula, R 103 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6Alkyl is a group that can be substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are substituted with halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 5 is 1 or 2), [ka] (In the formula, R 110 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 111 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 110 or R 111 C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein R 110 or R 111 C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 6 is 1 or 2), [ka] (In the formula, R 119 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a group that can be substituted with halogen, hydroxy, -NO2, and C 1~6and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 8 is 1 or 2), [ka] (In the formula, R 126 and R 127 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 9 is 1 or 2), [ka] (In the formula, R 134 and R 135 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 136 , and -C(O)NR 137 R 138 wherein C is independently selected from the group consisting of 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 10 is 1 or 2, where n 11 is 1 or 2, R 136 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 137 and R 138 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; [ka] (In the formula, R 144 and R 145 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, where n 12 is 1 or 2), [ka] (In the formula, R 146 is C 2~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 2~6 Alkyl is a halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, where n 13 is 1 or 2), [ka] (In the formula, R 148 is H or CH3, and R 149 is H or C optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl, -COOH, -NH, -C(O)NH, and -N(H)C(O)NH; 1~6 alkyl, and R 150 is H, CH3 or acetyl, where n 14 is 1 or 2), and [ka] (In the formula, n 15is either 1 or 2) is selected from the group consisting of R 5 Ha-NR 79 R 80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of the is H, and n 1 is 3 or 4, and R 6 is C optionally substituted with hydroxyl 1~6 alkyl, and R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 each of is independently H or CH3, and L is [ka] and chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0203] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NHR16 where R 16 is H or C 1~6 alkyl, and R N are (i) H, (ii) C 1~6 alkyl, (iii) -C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) —C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v) -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi) -C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii) —C(O)C 1~3 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) —C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and R1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 4 teeth, [ka] (In the formula, R 90 and R 91 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 2 is 3 or 4), [ka] (In the formula, R 99 and R 100 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 4 is 1 or 2), [ka] (In the formula, R 103 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is a group that can be substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are substituted with halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 5 is 1 or 2), [ka] (In the formula, R 110 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 111 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 110 or R 111 C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein R 110 or R 111 C6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 6 is 1 or 2), [ka] (In the formula, R 119 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a group that can be substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 8 is 1 or 2), [ka] (In the formula, R 134 and R 135 Each of these is H, C 1~6 Alkyl, C 6~10 Aryl, 5-10 membered heteroaryl, -C(O)R 136 , and -C(O)NR 137 R 138 wherein C is independently selected from the group consisting of 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 10 is 1 or 2, where n 11is 1 or 2, R 136 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 137 and R 138 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; [ka] (In the formula, R 144 and R 145 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, wherein C 6~10 Aryl and 5- to 10-membered heteroaryl are substituted with halogen, -OH, -NO2, C 1~6optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, and 5- to 10-membered heterocycloalkyl, where n 12 is 1 or 2), and [ka] (In the formula, n 15 is either 1 or 2) is selected from the group consisting of R 5 Ha-NR 79 R 80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of the is H, and n 1 is 3 or 4, and R 6 is C optionally substituted with hydroxyl 1~6 alkyl, and R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 each of is independently H or CH3, and L is [ka] and chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0204] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NHR 16 where R 16 is H or C 1~6 alkyl, and R N are (i) H, (ii) C 1~6 alkyl, (iii) -C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) —C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v) -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi) -C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii) —C(O)C 1~3 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) —C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and R 1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; R 4 teeth, [ka] (In the formula, R 99 and R 100 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 4 is 1 or 2), and [ka] (In the formula, R 110 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 111 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 110 or R 111 C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein R 110 or R 111 C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 6 is either 1 or 2) is selected from the group consisting of R 5 Ha-NR 79 R 80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of the is H, and n 1 is 3 or 4, and R 6 is C optionally substituted with hydroxyl 1~6 alkyl, and R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 each of is independently H or CH3, and L is [ka] and chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0205] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NHR 16 where R 16 is H or C 1~6 alkyl, and R N are (i) H, (ii) C 1~6 alkyl, (iii) -C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) —C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v) -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C1~6 alkyl), (vi) -C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii) —C(O)C 1~3 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) —C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and R 1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 4 teeth, [ka] (In the formula, R 99 and R 100 Each of these is H, C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl, where n 4 is 1 or 2), and [ka] (In the formula, R 110 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 111 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein n 6 is 1 or 2; 5 Ha-NR 79 R 80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of the is H, and n 1 is 3 or 4, and R 6 is C optionally substituted with hydroxyl 1~6 alkyl, and R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 each of is independently H or CH3, and L is [ka] and chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0206] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NHR 16 where R 16 is H or C 1~6 alkyl, and R N are (i) H, (ii) C 1~6 alkyl, (iii) -C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) —C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v) -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi) -C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii) —C(O)C 1~3Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) —C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and R 1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 4 teeth, [ka] (In the formula, R 99 and R 100 Each of H and C 1~6 alkyl, where n 4 is 1 or 2), and [ka] (In the formula, R 110 is H and R 111 is a C6 aryl, where n 6 is 1 or 2; 5 Ha-NR 79 R80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of the is H, and n 1 is 3 or 4, and R 6 is C optionally substituted with hydroxyl 1~6 alkyl, and R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 each of is independently H or CH3, and L is [ka] and chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0207] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NHR 16 where R 16 is H or C 1~6 alkyl, and R Nare (i) H, (ii) C 1~6 alkyl, (iii) -C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) —C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v) -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi) -C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii) —C(O)C 1~3 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) —C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and R 1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 4 teeth, [ka] (In the formula, R 99 and R 100 Each of H and C 1~6 alkyl, where n 4 is 1 or 2), and R 5 Ha-NR 79 R 80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of the is H, and n 1 is 3 or 4, and R 6 is C optionally substituted with hydroxyl 1~6 alkyl, and R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 9 , R 10 , R 11 , R12 , R 13 , R 14 , and R 15 each of is independently H or CH3, and L is [ka] and chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0208] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NHR 16 where R 16 is H or C 1~6 alkyl, and R N are (i) H, (ii) C 1~6 alkyl, (iii) -C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) —C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v) -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi) -C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii) —C(O)C 1~3 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) —C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and R 1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 4 teeth, [ka] (In the formula, R 99 and R 100 Each of is H, where n 4 is 1 or 2), and R 5 Ha-NR 79 R 80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82)NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of the is H, and n 1 is 3 or 4, and R 6 is C optionally substituted with hydroxyl 1~6 alkyl, and R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 each of is independently H or CH3, and L is [ka] and chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0209] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NHR 16 where R 16 is H or C 1~6 alkyl, and R N are (i) H, (ii) C 1~6 alkyl, (iii) -C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10aryl, and 5- to 10-membered heteroaryl), (iv) —C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v) -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi) -C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii) —C(O)C 1~3 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) —C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and R 1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 3 -C 1~3Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 4 teeth, [ka] and R 5 Ha-NR 79 R 80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of the is H, and n 1 is 3 or 4, and R 6 is C optionally substituted with hydroxyl 1~6 alkyl, and R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 each of is independently H or CH3, and L is [ka] and chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0210] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NHR 16 where R 16 is H or C 1~6 alkyl, and R N are (i) H, (ii) C 1~6 alkyl, (iii) -C(O)R 17 (In the formula, R 17 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (iv) —C(O)C 1~3 Alkylene-C(O)OR 18 (In the formula, R 18 is H or C 1~6 alkyl), (v) -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 (In the formula, R 19 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein R 20 is H or C 1~6 alkyl), (vi) -C(O)C 1~3 Alkylene-NR 21 R 22 (In the formula, R 21 and R 22 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), (vii) —C(O)C 1~3 Alkylene-C(O)NR 23 R 24 (In the formula, R 23 and R 24Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), and (viii) —C(O)C 1~3 Alkylene-S(O)R 25 (In the formula, R 25 is C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl), R 1 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 3 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 4 teeth [ka] and R 5 Ha-NR 79 R 80 and R 79 and R 80 Each of these is H, C 1~6 Alkyl, -C(O)R 81 , and -C(=NR 82 )NR 83 R 84 where R is independently selected from the group consisting of 81 is C 1~6 alkyl, and R 82 , R 83 , and R 84 Each of the is H, and n 1 is 3 or 4, and R 6 is C optionally substituted with hydroxyl 1~6alkyl, and R 8 -C 1~3 Alkylene (C 6~10 aryl), where C 6~10 Aryl is substituted with halogen, hydroxy, -NO2, and C 1~6 optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy; 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 each of is independently H or CH3, and L is [ka] and chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

[0211] An exemplary embodiment of the present invention includes a compound having the structure of Formula I, or a salt thereof, wherein R C is OH or NH2, and R N is H, C 1~3 Alkyl, -C(O)R 17 , -C(O)C 1~3 Alkylene-C(O)OR 18 , -C(O)C 1~3 Alkylene-N(R 20 )C(O)R 19 , -C(O)C 1~3 Alkylene-NR 21 R 22 , -C(O)C 1~3 Alkylene-C(O)NR 23 R 24 , and -C(O)C 1~3 Alkylene-S(O)R 25 where R 17 is C 1~6 alkyl or 5-6 membered heteroaryl, R 18is C 1~3 alkyl, and R 19 is C 1~3 alkyl or C6 aryl, and R 20 , R 21 , R 22 , R 23 and R 24 Each of is H and R 25 is a C6 aryl, and R 1 teeth [ka] where R 88 is H, halogen, hydroxyl or C 1~3 is alkoxy, and R 3 teeth [ka] where R 89 is H, halogen, hydroxyl or C 1~3 is an alkoxy, R 4 teeth, [ka] (In the formula, R 90 and R 91 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 2 is 3 or 4), [ka] (In the formula, R 96 is C1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 3 is 3 or 4), [ka] (In the formula, R 99 and R 100 Each of these is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl, wherein C 1~6 Alkyl is a halogen, -OH, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10 Aryl and 5-10 membered heteroaryl are substituted with halogen, -OH, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 4 is 1 or 2), [ka] (In the formula, R 103 is C 1~6 Alkyl, C 6~10 aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein C 1~6 Alkyl is a group that can be substituted with halogen, hydroxy, -NO2, and C 1~6 and optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, wherein C 6~10Aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are substituted with halogen, hydroxy, -NO2, and C 1~6 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, where n 5 is 1 or 2), [ka] (In the formula, R 110 is H, C 1~6 Alkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; R 111 is C 1~6 Alkyl, C 6~10 ary...

Claims

1. Formula I: 【Chemical 1】 Formula I or a salt thereof (wherein R Ｃ is OH or NHR １６ where R １６ is H or C optionally substituted with one or more substituents １～６ is alkyl, R Ｎ teeth, (i) H, (ii) C １～６ Alkyl, (iii)-C(O)R １７ (In the formula, R １７ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (iv)-C(O)C １～６ Alkylene -C(O)OR １８ (In the formula, R １８ is H or C optionally substituted with one or more substituents １～６ alkyl), (v) -C(O)C １～６ Alkylene-N(R ２０ ) C(O)R １９ (In the formula, R １９ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R ２０ is H or C １～６ alkyl), (vi)-C(O)C １～６ Alkylene -NR ２１ R ２２ (In the formula, R ２１ and R ２２ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (vii)-C(O)C １～６ Alkylene-C(O)NR ２３ R ２４ (In the formula, R ２３ and R ２４ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (viii)-C(O)C １～６ Alkylene-S(O) ２ R ２５ (In the formula, R ２５ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and (ix) -S(O) ２ R ２６ (In the formula, R ２６ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents. is selected from the group consisting of R １ is C １～６ Alkyl, C ６～１０ aryl, 5- to 10-membered heteroaryl, —C １～６ Alkylene (C ６～１０ aryl) and -C １～６ alkylene (5-10 membered heteroaryl), wherein said C １～６ alkyl, the C ６～１０ Aryl, —C １～６ Alkylene (C ６～１０ aryl) ６～１０ aryl, the 5- to 10-membered heteroaryl and —C １～６ The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, wherein —C １～６ Alkylene (C ６～１０ aryl) and -C １～６ The C of alkylene (5- to 10-membered heteroaryl) １～６ The alkylene is optionally substituted with one or more substituents; R ３ teeth, (i) C optionally substituted with one or more substituents ６～１０ aryl, (ii) 5-10 membered heteroaryl optionally substituted with one or more substituents; (iii)-C １～６ Alkylene (C ６～１０ aryl) (wherein ６～１０ Aryl is optionally substituted with one or more substituents, wherein １～６ alkylene optionally substituted with one or more substituents); (iv)-C １～６ alkylene(5-10 membered heteroaryl), wherein said 5-10 membered heteroaryl is optionally substituted with one or more substituents, １～６ alkylene optionally substituted with one or more substituents); (v)-C １～６ Alkylene -NR ２７ C(O)R ２８ (In the formula, R ２７ is H or C １～６ is alkyl, R ２８ is C １～６ Alkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, and —NR ２９ R ３０ wherein said C is selected from the group consisting of １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; Here, R ２９ and R ３０ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (vi)-(C ６～１０ (arylene)-C(O)NR ３１ R ３２ or -C １～６ Alkylene-(C ６～１０ (arylene)-C(O)NR ３１ R ３２ (In the formula, R ３１ and R ３２ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (vii)-(C ６～１０ (arylene)-NR ３３ R ３４ or -C １～６ Alkylene-(C ６～１０ (arylene)-NR ３３ R ３４ (In the formula, R ３３ and R ３４ Each of １～６ Alkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, —C(O)R ３５ , —C(O)NR ３６ R ３７ , and -SO ２ R ３８ wherein said C is independently selected from the group consisting of １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R ３５ is C １～６ Alkyl, C ６～１０ aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted by one or more substituents; R ３６ and R ３７ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R ３８ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (viii)-(C ６～１０ (arylene)-SO ２ NR ３９ R ４０ or -C １～６ Alkylene-(C ６～１０ (arylene)-SO ２ NR ３９ R ４０ (In the formula, R ３９ and R ４０ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (ix)-(C ６～１０ arylene)-(C １～６ alkylene)-NR ４１ R ４２ or -C １～６ Alkylene-(C ６～１０ arylene)-(C １～６ alkylene)-NR ４１ R ４２ (In the formula, R ４１ and R ４２ Each of １～６ Alkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, —C(O)R ４３ and —C(O)NR ４４ R ４５ wherein said C is independently selected from the group consisting of １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R ４３ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R ４４ and R ４５ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (x)-(C ６～１０ arylene)-OR ４６ or -C １～６ Alkylene-(C ６～１０ arylene)-OR ４６ (In the formula, R ４６ is H, C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, and (xi)-C １～６ Alkylene-(C ６～１０ arylene)-N(R ４７ )-C(O)-CHR ４８ -NR ４９ R ５０ (In the formula, R ４７ is H or CH ３ and R ４８ is H or hydroxyl, -COOH, -NH ２ , —C(O)NH ２ , and —N(H)C(O)NH ２ C optionally substituted with one or more substituents each independently selected from the group consisting of １～６ alkyl, and R ４９ and R ５０ each independently represents H, CH ３ or acetyl) is selected from the group consisting of R ４ teeth, (i)-C １～６ Alkylene-N(R ５３ )C(O)NR ５１ R ５２ (In the formula, R ５１ and R ５２ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R ５３ is H or C １～６ alkyl), (ii)-C １～６ Alkylene-N(R ５５ ) C(O)R ５４ (In the formula, R ５４ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R ５５ is H or C １～６ alkyl), (iii)-(C ６～１０ (arylene)-C(O)NR ５６ R ５７ or -C １～６ Alkylene-(C ６～１０ (arylene)-C(O)NR ５６ R ５７ (In the formula, R ５６ and R ５７ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (iv)-(C ６～１０ arylene)-N(R ５９ ) C(O)R ５８ or -C １～６ Alkylene-(C ６～１０ arylene)-N(R ５９ ) C(O)R ５８ (In the formula, R ５８ is C １～６ Alkyl, C ６～１０ aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents, where R ５９ is H or C １～６ alkyl), (v)-(C ６～１０ arylene)-N(R ６２ )C(O)NR ６０ R ６１ or -C １～６ Alkylene-(C ６～１０ arylene)-N(R ６２ )C(O)NR ６０ R ６１ (In the formula, R ６０ and R ６１ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R ６２ is H or C １～６ alkyl), (vi)-(C ６～１０ arylene)-N(R ６４ ) SO ２ R ６３ or -C １～６ Alkylene-(C ６～１０ arylene)-N(R ６４ ) SO ２ R ６３ (In the formula, R ６３ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R ６４ is H or C １～６ alkyl), (vii)-(C ６～１０ (arylene)-SO ２ NR ６５ R ６６ or -C １～６ Alkylene-(C ６～１０ (arylene)-SO ２ NR ６５ R ６６ (In the formula, R ６５ and R ６６ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (viii)-(C ６～１０ arylene)-(C １～６ alkylene)-NR ６７ R ６８ or -C １～６ Alkylene-(C ６～１０ arylene)-(C １～６ alkylene)-NR ６７ R ６８ (In the formula, R ６７ and R ６８ Each of １～６ Alkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, —C(O)R ６９ and —C(O)NR ７０ R ７１ wherein said C is independently selected from the group consisting of １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R ６９ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents; R ７０ and R ７１ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (ix)-(C ６～１０ (arylene)-NR ７２ R ７３ or -C １～６ Alkylene-(C ６～１０ (arylene)-NR ７２ R ７３ (In the formula, R ７２ and R ７３ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (x)-(C ６～１０ arylene)-OR ７４ or -C １～６ Alkylene-(C ６～１０ arylene)-OR ７４ (In the formula, R ７４ is H, C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (xi)-C １～６ Alkylene-(C ６～１０ arylene)-N(R ７５ )-C(O)-CHR ７６ -NR ７７ R ７８ (In the formula, R ７５ is H or CH ３ and R ７６ is H or hydroxyl, -COOH, -NH ２ , —C(O)NH ２ , and —N(H)C(O)NH ２ C optionally substituted with one or more substituents each independently selected from the group consisting of １～６ alkyl, and R ７７ and R ７８ each independently represents H, CH ３ or acetyl), and (xii)-C １～６ Alkylene-(C ６～１０ Arylene)-CN is selected from the group consisting of R ５ teeth, (i) -NR ７９ R ８０ (In the formula, R ７９ and R ８０ Each of １～６ Alkyl, —C(O)R ８１ , and -C(=NR ８２ ) NR ８３ R ８４ or R ７９ and R ８０ together with the N atom to which they are attached form a 5- to 10-membered heteroaryl or a 5- to 10-membered heterocycloalkyl, wherein said C １～６ alkyl is optionally substituted with one or more substituents, wherein said 5- to 10-membered heteroaryl and 5- to 10-membered heterocycloalkyl are optionally substituted with one or more substituents; R ８１ is H, -NH ２ , C １～１６ Alkyl, C １～６ Haloalkyl, C ６～１０ selected from the group consisting of aryl, and 5- to 10-membered heteroaryl; R ８２ , R ８３ , and R ８４ Each of １～１６ Alkyl, C １～６ Haloalkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), and (ii) -N ＋ R ８５ R ８６ R ８７ (In the formula, R ８５ , R ８６ , and R ８７ Each of the is independently C １～６ alkyl) is selected from the group consisting of n １ is 1, 2, 3, 4, 5, or 6, R ６ is C optionally substituted with one or more substituents １～６ is alkyl, R ８ is C １～６ Alkyl, C ６～１０ aryl, 5- to 10-membered heteroaryl, —C １～６ Alkylene (C ６～１０ aryl) and -C １～６ alkylene (5-10 membered heteroaryl), wherein said C １～６ alkyl, the C ６～１０ Aryl, —C １～６ Alkylene (C ６～１０ aryl) ６～１０ aryl, the 5- to 10-membered heteroaryl and —C １～６ The 5- to 10-membered heteroaryl of alkylene(5- to 10-membered heteroaryl) is optionally substituted with one or more substituents, wherein —C １～６ Alkylene (C ６～１０ aryl) and -C １～６ The C of alkylene (5- to 10-membered heteroaryl) １～６ The alkylene is optionally substituted with one or more substituents; R ９ is H or C １～６ is alkyl, R １０ is H or C １～６ is alkyl, R １１ is H or C １～６ is alkyl, R １２ is H or C １～６ is alkyl, R １３ is H or C １～６ is alkyl, R １４ is H or C １～６ is alkyl, R １５ is H or C １～６ is alkyl, L is, 【Chemistry 2】 wherein X is S or O, and 【Chemistry 3】 is selected from the group consisting of The chiral center *1 is in the S or R configuration; The chiral center *2 is in the S configuration or the R configuration, The chiral center *3 is in the S configuration or the R configuration, The chiral center *4 is in the S configuration or the R configuration, The chiral center *5 is in the S configuration or the R configuration; The chiral center *6 is in the S configuration or the R configuration; The chiral center *7 is in the S configuration or the R configuration; The chiral center *8 is in the S configuration or the R configuration; however, i) R Ｃ NH ２ and R Ｎ is H or —C(O)CH ２ N ３ and R １ but, 【Chemistry 4】 and R ３ but, 【Chemistry 5】 and R ５ NH ２ and n １ is 4 and R ６ -CH(OH)(CH ３ ) and R ８ but, 【Chemistry 6】 and R ９ , R １０ , R １１ , R １２ , R １３ , R １４ and R １５ Each of the is H and L is 【Chemistry 7】 If ４ but 【Chemistry 8】 and ii) R Ｃ NH ２ and R Ｎ is H and R １ but 【Chemistry 9】 and R ３ but 【Chemistry 10】 and R ５ NH ２ and n １ is 4 and R ６ -CH(CH ３ ) ２ and R ８ -CH(OH)(CH ３ ) and R ９ , R １０ , R １１ , R １２ , R １３ , R １４ and R １５ Each of the is H and L is 【Chemistry 11】 If ４ but 【Chemistry 12】 (Provided that it is not a

2. R ４ but, (i)-C １～６ Alkylene-N(R ５３ )C(O)NR ５１ R ５２ (In the formula, R ５１ and R ５２ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ５３ is H or C １～６ alkyl), (ii)-C １～６ Alkylene-(C ６～１０ (arylene)-C(O)NR ５６ R ５７ (In the formula, R ５６ and R ５７ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (iii)-C １～６ Alkylene-(C ６～１０ arylene)-N(R ５９ ) C(O)R ５８ (In the formula, R ５８ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ５９ is H or C １～６ alkyl), (iv)-C １～６ Alkylene-(C ６～１０ arylene)-N(R ６２ )C(O)NR ６０ R ６１ (In the formula, R ６０ is H, C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; R ６１ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ６０ or R ６１ The above C １～６ Alkyl is optionally substituted with one or more substituents, where R ６０ or R ６１ The above C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R ６２ is H or C １～６ alkyl), (v)-C １～６ Alkylene-(C ６～１０ arylene)-N(R ６４ ) SO ２ R ６３ (In the formula, R ６３ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ６４ is H or C １～６ alkyl), (vi)-C １～６ Alkylene-(C ６～１０ arylene)-(C １～６ alkylene)-NR ６７ R ６８ (In the formula, R ６７ and R ６８ Each of １～６ Alkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, —C(O)R ６９ and —C(O)NR ７０ R ７１ are independently selected from the group consisting of R ６９ is C １～６ Alkyl, C ６～１０ selected from the group consisting of aryl, and 5- to 10-membered heteroaryl; R ７０ and R ７１ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), (vii)-C １～６ Alkylene-(C ６～１０ (arylene)-NR ７２ R ７３ (In the formula, R ７２ and R ７３ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), and (viii)-C １～６ Alkylene-(C ６～１０ Arylene)-CN 2. The compound or salt of claim 1 selected from the group consisting of:

3. R ４ but, (i)-C ３～４ Alkylene-N(R ５３ )C(O)NR ５１ R ５２ (In the formula, R ５１ and R ５２ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ５３ is H or C １～６ alkyl), (ii)-C １～２ Alkylene-(C ６ (arylene)-C(O)NR ５６ R ５７ (In the formula, R ５６ and R ５７ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein said C １～６ Alkyl is optionally substituted with one or more substituents, wherein said C ６～１０ aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents); (iii)-C １～２ Alkylene-(C ６ arylene)-N(R ５９ ) C(O)R ５８ (In the formula, R ５８ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ５９ is H or C １～６ alkyl), (iv)-C １～２ Alkylene-(C ６ arylene)-N(R ６２ )C(O)NR ６０ R ６１ (In the formula, R ６０ is H, C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; R ６１ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ６０ or R ６１ The above C １～６ Alkyl is optionally substituted with one or more substituents, where R ６０ or R ６１ The above C ６～１０ The aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents, where R ６２ is H or C １～６ alkyl), (v)-C １～２ Alkylene-(C ６ arylene)-N(R ６４ ) SO ２ R ６３ (In the formula, R ６３ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ６４ is H or C １～６ alkyl), (vi)-C １～２ Alkylene-(C ６ arylene)-(C １～２ alkylene)-NR ６７ R ６８ (In the formula, R ６７ and R ６８ Each of １～６ Alkyl, C ６～１０ Aryl, 5- to 10-membered heteroaryl, —C(O)R ６９ and —C(O)NR ７０ R ７１ are independently selected from the group consisting of R ６９ is C １～６ Alkyl, C ６～１０ selected from the group consisting of aryl, and 5- to 10-membered heteroaryl; R ７０ and R ７１ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), (vii)-C １～２ Alkylene-(C ６ (arylene)-NR ７２ R ７３ (In the formula, R ７２ and R ７３ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), and (viii)-C １～２ Alkylene-(C ６ Arylene)-CN 3. The compound or salt of claim 1, selected from the group consisting of:

4. R ４ But, -C ３～４ Alkylene-N(R ５３ )C(O)NR ５１ R ５２ , -C １～２ Alkylene-(C ６ (arylene)-C(O)NR ５６ R ５７ , -C １～２ Alkylene-(C ６ arylene)-N(R ５９ ) C(O)R ５８ , -C １～２ Alkylene-(C ６ arylene)-N(R ６２ )C(O)NR ６０ R ６１ , -C １～２ Alkylene-(C ６ arylene)-N(R ６４ ) SO ２ R ６３ , -C １～２ Alkylene-(C ６ arylene)-(C １～２ alkylene)-NR ６７ R ６８ , -C １～２ Alkylene-(C ６ (arylene)-NR ７２ R ７３ , and -C １～２ Alkylene-(C ６ arylene)-CN, wherein R ５１ , R ５２ , R ５３ , R ５６ , R ５７ , R ５９ , R ６０ , R ６２ and R ６４ each of which is H, and R ５８ and R ６３ Each of the is independently C ６～１０ aryl, and R ６１ is C １～３ C optionally substituted with alkoxy ６～１０ aryl, and R ６７ and R ６８ each of which is H, —C(O)R ６９ and —C(O)NR ７０ R ７１ where R ６９ is C １～６ alkyl, and R ７０ and R ７１ each of which is H, and R ７２ and R ７３ Each of １～６ The compound or salt of any one of claims 1 to 3, wherein the compound or salt is independently selected from the group consisting of alkyl.

5. R ４ But, -C １～６ Alkylene-(C ６～１０ (arylene)-C(O)NR ５６ R ５７ or -C １～６ Alkylene-(C ６～１０ arylene)-N(R ６２ )C(O)NR ６０ R ６１ where R ５６ and R ５７ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; R ６０ is H, C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; R ６１ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; R ６２ is H or C １～６ alkyl, where R ５６ , R ５７ , R ６０ or R ６１ The above C １～６ Alkyl is optionally substituted with one or more substituents, R ５６ , R ５７ , R ６０ or R ６１ The above C ６～１０ 3. The compound or salt of claim 1, wherein the aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

6. R ４ But, -C １～２ Alkylene-(C ６ (arylene)-C(O)NR ５６ R ５７ or -C １～２ Alkylene-(C ６ arylene)-N(R ６２ )C(O)NR ６０ R ６１ where R ５６ and R ５７ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; R ６０ is H, C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; R ６１ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; R ６２ is H or C １～６ alkyl, where R ５６ , R ５７ , R ６０ or R ６１ The above C １～６ Alkyl is optionally substituted with one or more substituents, R ５６ , R ５７ , R ６０ or R ６１ The above C ６～１０ 6. The compound or salt of claim 5, wherein the aryl and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents.

7. R ４ but, 【Chemistry 13】 where R １０１ and R １０２ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl; R １１８ is H, halogen, hydroxy, -NO ２ , and C １～６ 7. The compound or salt of claim 6, wherein the compound or salt is selected from the group consisting of alkoxy.

8. R ４ but, 【Chemistry 14】 8. The compound or salt of claim 7, wherein:

9. R ４ but 【Chemistry 15】 9. The compound or salt of claim 8, wherein:

10. R ４ But, -C ３～４ Alkylene-N(R ５３ )C(O)NR ５１ R ５２ and R ５３ is H and R ５１ and R ５２ The compound or salt of any one of claims 1 to 4, wherein each of is H.

11. R ４ But, -C １ Alkylene-(C ６ arylene)-N(R ５９ ) C(O)R ５８ and R ５９ is H and R ５８ The compound or salt according to any one of claims 1 to 4, wherein is phenyl.

12. R ４ But, -C １ Alkylene-(C ６ arylene)-N(R ６４ ) SO ２ R ６３ and R ６４ is H and R ６３ The compound or salt according to any one of claims 1 to 4, wherein is phenyl.

13. R ４ But, -C １ Alkylene-(C ６ arylene)-(C １ alkylene)-NR ６７ R ６８ where R ６７ and R ６８ is H or R ６７ is H and R ６８ -C(O)NR ７０ R ７１ and R ７０ and R ７１ The compound or salt of any one of claims 1 to 4, wherein each of is H.

14. R ４ But, -C １ Alkylene-(C ６ (arylene)-NR ７２ R ７３ and R ７２ is H and R ７３ is C １～６ The compound or salt according to any one of claims 1 to 4, wherein the aryl group is alkyl.

15. R ４ But, -C １ Alkylene-(C ６ The compound or salt according to any one of claims 1 to 4, wherein the compound or salt is (arylene)-CN.

16. R ５ But, -NR ７９ R ８０ and R ７９ and R ８０ Each of １～６ Alkyl, —C(O)R ８１ , and -C(=NR ８２ ) NR ８３ R ８４ where R ８１ is C １～６ alkyl, and R ８２ , R ８３ , and R ８４ 16. The compound or salt of any one of claims 1 to 15, wherein each of is H.

17. R ５ But, -NR ７９ R ８０ and R ７９ and R ８０ Each of １～６ 17. The compound or salt of claim 16, wherein each of the aryl, ...

18. R ５ But -NH ２ , -NHCH ３ or -N(CH ３ ) ２ 18. The compound or salt of claim 17, wherein:

19. R ５ Ga-NH ２ 19. The compound or salt of claim 18, wherein:

20. R ５ Ga-NHCH ３ 19. The compound or salt of claim 18, wherein:

21. R ５ -N(CH ３ ) ２ 19. The compound or salt of claim 18, wherein:

22. n １ The compound or salt according to any one of claims 1 to 21, wherein is 3 or 4.

23. n １ 23. The compound or salt of claim 22, wherein is 4.

24. R Ｃ is OH or NH ２ The compound or salt according to any one of claims 1 to 23,

25. R Ｃ NH ２ 25. The compound or salt of claim 24, wherein:

26. R Ｎ but, (i) H, (ii) C １～６ Alkyl, (iii)-C(O)R １７ (In the formula, R １７ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), (iv)-C(O)C １～６ Alkylene -C(O)OR １８ (In the formula, R １８ is H or C １～６ alkyl), (v) -C(O)C １～６ Alkylene-N(R ２０ ) C(O)R １９ (In the formula, R １９ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ２０ is H or C １～６ alkyl), (vi)-C(O)C １～６ Alkylene -NR ２１ R ２２ (In the formula, R ２１ and R ２２ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), (vii)-C(O)C １～６ Alkylene-C(O)NR ２３ R ２４ (In the formula, R ２３ and R ２４ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), (viii)-C(O)C １～６ Alkylene-S(O) ２ R ２５ (In the formula, R ２５ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), and (ix) -S(O) ２ R ２６ (In the formula, R ２６ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl 26. The compound or salt of any one of claims 1 to 25, selected from the group consisting of:

27. R Ｎ but, (i) H, (ii) C １～６ Alkyl, (iii)-C(O)R １７ (In the formula, R １７ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), (iv)-C(O)C １～３ Alkylene -C(O)OR １８ (In the formula, R １８ is H or C １～６ alkyl), (v) -C(O)C １～３ Alkylene-N(R ２０ ) C(O)R １９ (In the formula, R １９ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, wherein R ２０ is H or C １～６ alkyl), (vi)-C(O)C １～３ Alkylene -NR ２１ R ２２ (In the formula, R ２１ and R ２２ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), (vii)-C(O)C １～３ Alkylene-C(O)NR ２３ R ２４ (In the formula, R ２３ and R ２４ Each of １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl), and (viii)-C(O)C １～３ Alkylene-S(O) ２ R ２５ (In the formula, R ２５ is C １～６ Alkyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl 27. The compound or salt of claim 26, selected from the group consisting of:

28. R Ｎ But H, C １～６ Alkyl, —C(O)R １７ , -C(O)C １～６ Alkylene -C(O)OR １８ , -C(O)C １～６ Alkylene-N(R ２０ ) C(O)R １９ , -C(O)C １～６ Alkylene -NR ２１ R ２２ , -C(O)C １～６ Alkylene-C(O)NR ２３ R ２４ , and -C(O)C １～６ Alkylene-S(O) ２ R ２５ where R １７ is C １～６ alkyl or 5- to 6-membered heteroaryl, and R １８ is C １～６ alkyl, and R １９ is C １～６ Alkyl or C ６ aryl, and R ２０ , R ２１ , R ２２ , R ２３ and R ２４ each of which is H, and R ２５ is C ６ 27. The compound or salt of claim 26, which is aryl.

29. R Ｎ But H, C １～３ Alkyl, —C(O)R １７ , -C(O)C １～３ Alkylene -C(O)OR １８ , -C(O)C １～３ Alkylene-N(R ２０ ) C(O)R １９ , -C(O)C １～３ Alkylene -NR ２１ R ２２ , -C(O)C １～３ Alkylene-C(O)NR ２３ R ２４ , and -C(O)C １～３ Alkylene-S(O) ２ R ２５ where R １７ is C １～６ alkyl or 5- to 6-membered heteroaryl, and R １８ is C １～３ alkyl, and R １９ is C １～３ Alkyl or C ６ aryl, and R ２０ , R ２１ , R ２２ , R ２３ and R ２４ each of which is H, and R ２５ is C ６ 29. The compound or salt of claim 28, which is aryl.

30. R Ｎ 30. The compound or salt of claim 29, wherein is H.

31. R １ But, -C １～３ Alkylene (C ６～１０ aryl), wherein said C ６～１０ Aryl is halogen, hydroxy, -NO ２ , and C １～６ 31. The compound or salt of any one of claims 1 to 30, optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

32. R １ But, -C １～２ Alkylene (C ６ aryl), wherein said C ６ Aryl is a halogen, hydroxyl, -NO ２ , and C １～６ 32. The compound or salt of claim 31, optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

33. R １ but 【Chemistry 16】 where R ８８ is H, halogen, hydroxyl or C １～３ 33. The compound or salt of claim 32, which is alkoxy.

34. R ８８ 34. The compound or salt of claim 33, wherein is Cl.

35. R ３ But, -C １～３ Alkylene (C ６～１０ aryl), wherein said C ６～１０ Aryl is halogen, hydroxy, -NO ２ , and C １～６ 35. The compound or salt of any one of claims 1 to 34, optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

36. R ３ But, -C １～２ Alkylene (C ６ aryl), wherein said C ６ Aryl is a halogen, hydroxyl, -NO ２ , and C １～６ 36. The compound or salt of claim 35, optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

37. R ３ but 【Chemistry 17】 where R ８９ is H, halogen, hydroxyl or C １～３ 37. The compound or salt of claim 36, which is alkoxy.

38. R ８９ 38. The compound or salt of claim 37, wherein is Cl or hydroxyl.

39. R ８９ 39. The compound or salt of claim 38, wherein is hydroxyl.

40. R ６ C optionally substituted with hydroxyl １～６ 40. The compound or salt of any one of claims 1 to 39, which is alkyl.

41. R ６ But -CH(CH ３ )OH, -CH(CH ３ ) ２ , -C(CH ３ ) ３ , -CH ２ OH and -CH ２ CH ３ 41. The compound or salt of claim 40, selected from the group consisting of:

42. R ６ -CH(CH ３ 42. The compound or salt of claim 41, wherein:

43. R ８ But, -C １～３ Alkylene (C ６～１０ aryl), wherein said C ６～１０ Aryl is halogen, hydroxy, -NO ２ , and C １～６ 43. The compound or salt of any one of claims 1 to 42, optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

44. R ８ But, -C １～２ Alkylene (C ６ aryl), wherein said C ６ Aryl is a halogen, hydroxyl, -NO ２ , and C １～６ 44. The compound or salt of claim 43, optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy.

45. R ８ but 【Chemistry 18】 where R １５１ is H, halogen, hydroxyl or C １～３ 45. The compound or salt of claim 44, which is alkoxy.

46. R １５１ 46. The compound or salt of claim 45, wherein is Cl or hydroxyl.

47. R １５１ 47. The compound or salt of claim 46, wherein is hydroxyl.

48. R ９ , R １０ , R １１ , R １２ , R １３ , R １４ , and R １５ each independently is H or C １～３ 48. The compound or salt of any one of claims 1 to 47, which is alkyl.

49. R ９ , R １０ , R １１ , R １３ , R １４ , and R １５ 49. The compound or salt of claim 48, wherein each of is H.

50. R １２ is H or CH ３ 50. The compound or salt of claim 48 or 49, wherein:

51. R １２ 51. The compound or salt of claim 50, wherein is H.

52. L 【Chemistry 19】 52. The compound or salt according to any one of claims 1 to 51,

53. The compound or salt according to any one of claims 1 to 52, wherein chiral center *1 is in the S configuration, chiral center *2 is in the S configuration, chiral center *3 is in the S configuration, chiral center *4 is in the R configuration, chiral center *5 is in the S configuration, chiral center *6 is in the S configuration, chiral center *7 is in the R configuration, and chiral center *8 is in the R configuration.

54. A compound selected from Table 5 or a salt thereof.

55. 55. The compound of claim 54, wherein the compound is compound 1, 4, 7, 8, 12, 14, 15, 24, 25, 27, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 71, 72, 77, 78, or 79, or a salt thereof.

56. 55. The compound of claim 54, wherein the compound is compound 1, 4, 7, 12, 14, 15, 24, 25, 27, 32, 34, 35, 36, 37, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 71, 72, 77, 78, or 79, or a salt thereof.

57. 55. The compound of claim 54, wherein the compound is compound 15, 24, 25, 32, 42, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 72, 77, or 78, or a salt thereof.

58. 55. The compound of claim 54, wherein the compound is compound 15, 24, 25, 32, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, or 77, or a salt thereof.

59. 55. The compound of claim 54, wherein the compound is compound 15, 24, 46, 47, 48, 50, 51, 52, or 56, or a salt thereof.

60. 60. A pharmaceutical composition comprising a compound as defined in any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

61. 61. The pharmaceutical composition of claim 60 for use in inhibiting the activity of the SSTR2 receptor in a subject.

62. 61. The pharmaceutical composition of claim 60 for use in the prevention or treatment of hypoglycemia in a subject.

63. 63. The pharmaceutical composition of claim 62, wherein the hypoglycemia is insulin-induced hypoglycemia.

64. 61. The pharmaceutical composition of claim 60 for use in treating diabetes in a subject.

65. 60. A method of inhibiting the activity of the SSTR2 receptor in a subject, comprising administering to a subject in need thereof a compound according to any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof.

66. 60. A method for preventing or treating hypoglycemia in a subject, comprising administering to a subject in need thereof a compound according to any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof.

67. 67. The method of claim 66, wherein the hypoglycemia is insulin-induced hypoglycemia.

68. 60. A method of treating diabetes in a subject, comprising administering to a subject in need thereof a compound according to any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof.

Images