RU2415134C2 - Method of treatment or prevention of physiological and/or pathophysiological conditions mediated by growth hormone secretion stimulating receptors, triazole and based pharmaceutical composition - Google Patents

Abstract

FIELD: medicine, pharmaceutics. ^ SUBSTANCE: present invention refers to administration of formula (I) described new triazole derivatives as greline-like ligands of growth hormone secretion stimulating receptors (GHSS receptors) that can be effective in treatment or prevention of GHSS receptors mediated physiological and/or pathophysiological conditions in mammals, preferentially in humans. Formula (I): where R1 is chosen from a group including hydrogen atom, (C1-C12)alkyl phenyl, naphthyl, (C5-C14)phenyl(C1-C12)alkyl, indolylalkyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -CI, -Br, -I, -NO2, (C1-C12)alkyl, phenyl, naphthyl, -O-(C1-C12)alkyl; R2 is chosen from a group including (C1-C12)alkyl, phenyl, naphthyl, (C5-C14)phenyl (C1-C12)alkyl, indolylalkyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -Cl, -Br, -I, -NO2, (C1-C12)alkyl, phenyl, naphthyl, -O-(C1-C12)alkyl; one of radicals R3 and R4 represents hydrogen atom, and other radical are chosen from a group including hydrogen atom, phenyl, naphthyl, indolylalkyl; R5 is chosen from a group including hydrogen atom, phenyl, naphthyl, -CO-(C3-C8)cycloalkyl, -CO-phenyl, -CO-(C5-C7)heteroaryl containing 1, 2 nitrogen atoms, -CO-(C3-C7)heteroaryl(C1-C4)alkyl containing 1, 2 nitrogen atoms, -CO-(C5-C6)heterocyclyl containing 1, 2 nitrogen or oxygen atoms, -CO-C*(R9R10)-NH2, -CO-CH2-C*(R9R10)-NH2, -CO-C*(R9R10)-CH2-NH2, phenylsulfonyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -CI, -Br, -I, -N3, -CN, -NR7R8, -OH, -NO2, (C1-C4)alkyl; R6 represents hydrogen atom; R7 and R8 represent hydrogen atom; R9 and R10 are independently chosen from a group including hydrogen atom and (C1-C4)alkyl; m relates to 0, 1 or 2, and preferentially 0; and * means carbon atom in a R or S configurations, if it is chiralene. ^ EFFECT: invention refers to GHSS receptors antagonists and agonists which can be used for modulation of these receptors and are effective in treatment of said conditions, particularly growth impairment, cachexia, short-term, intermediate and/or long-term energy balance control; short-term, intermediate and/or long-term food intake control (stimulation and/or suppression); adipogenesis, adiposity and/or obesity; body weight growth and/or reduction in mammals. ^ 22 cl, 6 tbl, 15 ex, 46 dwg

Description

FIELD OF THE INVENTION

The present invention relates to new derivatives of triazoles, functioning as ghrelin-like ligands of receptors that stimulate the secretion of growth hormone. These compounds are useful in modulating the content of growth hormone in the plasma of mammals, as well as in the treatment and / or regulation of various physiological and pathophysiological conditions, such as stunted growth, obesity, food intake, energy balance, tumor cell proliferation, wound / burn healing, metabolic disorders and inflammatory processes.

State of the art

Ghrelin, a 28 amino acid long peptide with a unique octanoyl modification at the Ser-3 position (Kojima M et al., Nature 1999, 402: 656-660), has been identified as an endogenous growth hormone receptor type 1a ligand (GHS-R 1a) which is a G-protein coupled receptor (GPCR, Howard AD et al., Science 1996, 273: 974-977). Mostly, ghrelin is produced in the upper intestinal tract and stomach, but small amounts have also been found in the intestines, pancreas, kidneys, immune cells, placenta, testes, pituitary gland, lungs and hypothalamus (van der Lely AJ et al., Endocrine Rev. 2004, 25: 426-457; Cowley M et al., Neuron 2003, 37: 649-661). In humans, ghrelin stimulates growth hormone (GH) in a manner independent of the GHRH receptor and the synergistic effect of GHRH on GH secretion (Arvat E et al., J. Clin. Endocrinol. Metab. 2001, 86: 1169-1174). In addition, it also stimulates the secretion of ACTH, prolactin, cortisol, aldosterone and epinephrine (Arvat E et al., J. Clin. Endocrinol. Metab. 2001, 86: 1169-1174; Nagaya N et al., Am. J. Physiol Regul. Integr, Comp. Physiol. 2001, 280: R1483-1487; Takaya K et al., J. Clin. Endocrinol. Metab. 2000, 85: 4908-4911). It is believed that ghrelin is involved in the regulation of metabolism and energy expenditure, and therefore it is believed that the expression of ghrelin and its release into the blood from the stomach can be affected by hormones that determine metabolism. In obese people, the plasma ghrelin content is reduced, suggesting that an increase in insulin or leptin levels in such people may lead to a decrease in ghrelin secretion (Tschop M et al, Diabetes 2001, 50: 707-709).

It is also believed that the release of growth hormone in humans and animals can treat physiological and pathophysiological conditions characterized by insufficient secretion of growth hormones, as well as conditions that can be improved by the anabolic effects of such a hormone.

The initial clinical use of growth hormone (GH) was limited to the treatment of growth hormone deficiency in children, but the commercialization of recombinant human growth hormone (rhGH) made numerous studies showing other potential clinical applications of GH possible (Strobl JS et al., Pharmacol. Rev. 1994, 46: 1-34; Torosian MH, J. Pediatr. Endocrinol. 1993, 6: 93-97). It turned out that rhGH can be promising in the treatment of burns, wounds, bone fractures, and it has recently been found that it can reverse the catabolic effects of glucocorticoids, chemotherapy and AIDS, as well as modify the composition of the body (Rudman D et al., N. Engl. J . Med. 1990, 323: 1-6; Papadakis MA et al., Ann. Intern. Med. 1996, 124: 708-716; Welle S et al., J. Clin. Endocrinol. Metab. 1996, 81: 3239 -3243).

The synthesized and accumulated in the pituitary GH is released under the control of two known hypothalamic hormones: somatotropin-releasing factor, hormone that stimulates the release of the hormone by the pituitary gland (GHRH), and the inhibitory hormone, somatostatin (SRIF). In most cases, GH deficiency is not associated with pituitary deficiency, but with defects in the hypothalamus. Thus, an alternative rhGH treatment for patients with GH deficiency is the use of compounds releasing endogenous GH from the pituitary gland. This treatment can be carried out using GHRH, which stimulates the release of GH, but it is also possible with the help of synthetic growth hormone secretion stimulants (synthetic SSHR).

It has been shown that a large number of synthetic, peptidyl and non-peptidyl SSHRs, such as GHRP 1, 2 and 6, hexarelin, MK-0677 and EP-01572, specifically bind to the orphan receptor (SSHR receptor), and some of them were known long before discoveries of ghrelin receptors and ghrelin / SSHR receptors (for further information see Camanni F et al., Front Neuroendochnol. 1998, 19: 47-72; Casa-nueva Fet al., Trends Endocrinol. Metab. 1999, 10: 30-38 ";" van der Lely AJ et al., Endocrine Rev. 2004, 25: 426-457 "). GCGR also demonstrates the powerful ability to release GH and has the same biological effect as described above for ghrelin. GCGR is also described in the following patents or patent applications: US 6071926, US 6329342, US 6194578, US 2001/0041673, US 6,251,902, US 2001/0020012, US 2002/0013320, US 2002/0002137, WO 95/14666, WO 96 / 15148, WO 01/96300.

Ghrelin / SSHG-induced release (secretion) of GH is mediated by activation of ghrelin / SSHG receptors of type 1a (GHS-R 1a), however, there is evidence at present that at least some of the other effects of ghrelin and SSHG are also mediated by various SSHG family receptors or even various sites (centers) of binding of this SSHR receptor. GCGR receptors are concentrated in the pituitary-hypothalamic region, but are apparently distributed in other central and peripheral tissues (Hattori N et al., J. Clin. Endocrinol. Metab. 2001, 86: 4284-4291; Gnanapavan S et al., J. Clin. Endocrinol. Metab. 2002, 87: 2988-2991; Muccioli G et al., J. Endocrinol. 2000, 157: 99-106; Muccioli G et al., Ann. Endocrinol. 2000, 61 : 27-31; Muccioli G et al., Eur. J. Pharmacol. 2002, 440: 235-254; Papotti M et al., J. Clin. Endocrinol. Metab. 2000, 85: 3803-3807; Cassoni P et al., J. Clin. Endocrinol. Metab. 2001, 86: 1738-1745; Guan XM et al., Brain Res. Mol. Brain Res. 1997, 48: 23-29; Bluet-Pajot MT et al., Endocrine 2001, 14: 1-8; Korbonits M et al., J. Clin. Endocrinol. Metab. 1998, 83: 3624-3630).

Currently, two first-type SSHRs have been identified, GHS-R 1a and GHS-R 1b; in humans, they are thought to be expressed by the same gene, then undergoing different splicing (van der Lely AJ et al., Endocrine Rev. 2004, 25: 426-457; Howard AD et al., Science 1996, 273: 974-977; Smith RG et al., Endocr. Rev. 1997, 18: 621-645; Smith RG et al., Endocrine 2001, 14: 9- 14; McKee KK et al., Mol. Endocrinol. 1997, 11: 415-423; Petersenn S, Minerva Endocrinol. 2002; 27: 243-256). Among mammals, a high degree of sequence identity has been reported for GHS-R 1a (Petersenn S, Minerva Endocrinol. 2002; 27: 243-256: 91.8% to 95.6%). The motilin receptor was discovered as a member of the SSHR family of receptors, its identity is 52% (Smith RG et al., Endocrine 2001, 14: 9-14; McKee KK et al., Genomics 1997, 46: 426-434). The gastrointestinal motilin receptor 1a and GHS-R 1a show a high degree of similarity (Smith RG et al., Endocrine 2001, 14: 9-14; Feighner SD et al., Science 1999, 284: 2184-2188).

Other receptors for the SSHR family are the neurotensin receptor, TRH receptor, GPR38 (FM1), GPR39 (FM2) and FM3 (Smith RG et al., Endocr. Rev. 1997, 18: 621-645; Smith RG et al., Horm. Res. 1999, 51 (Suppl. 3): 1-8; Tan CP et al., Genomics 1998, 52: 223-229; Howard AD et al., Science 1996, 273: 974-977). It seems that in a large number of central and peripheral tissues there are other subtypes of SSHR receptors (van der Lely AJ et al., Endocrine Rev. 2004, 25: 426-457). For example, the presence of GHS-R in the heart has been reported (Bodart V et al., Circ. Res. 1999, 85: 796-802), suggesting that its sequence is similar to that of CD36, a multifunctional receptor called glycoprotein IV (Bodart V et al., Circ. Res. 2002, 90: 844-849). Cassoni et al. (J. Clin. Endocrinol. Metab. 2001, 86: 1738-1745) reported the presence of GHS-R subtypes in mammalian neoplastic cells activated by ligands that bind to specific sites other than classical GHS-R type 1. More Moreover, the data obtained by these authors support the hypothesis that in peripheral organs GHS-R

there are even various subtypes of binding sites, possibly due to their endocrine or non-endocrine, as well as normal or neoplastic nature.

The ubiquity of the binding sites of SSHR is explained by the fact that, in addition to the properties of strong secretagogues of growth hormones, ghrelin and synthetic SSHH are involved in the implementation of several important physiological and pathophysiological functions.

Accordingly, potential clinical applications include the following:

a) Short-term, medium-term and long-term regulation of energy balance and / or food intake (Tschop M et al., Nature 2000, 407: 908-913; Asakawa A et al., Gut 2003, 52: 947-952; US 2001/0020012 ; Kojima M et al., Curr. Opin. Pharmacol. 2002, 2: 665-668; Horvath TL et al., Curr. Pharm. Des. 2003, 9: 1383-1395; Wren AM et al., J. Clin Endocrinol. Metab. 2001, 86: 5992-5995).

The expression of GHS-R1a in neurons of the paraventricular nuclei of the hypothalamus is shown. The efferents of these neurons are included in key hypothalamic chains of control of food intake, for example, in the arcuate nucleus producing the mediator neuropeptide Y (NPY). It is believed that stimulation of food intake by ghrelin and / or GCGR is mediated by the accumulation of NPY in the arcuate core (Willesen MG et al., Neuroendocrin. 1999, 70: 306-316). A single injection (intracerebral injection (in the ventricular region, intracerebroventricular-icv) or intraperitoneal injection-ip) of anti-ghrelin IgG inhibited acute eating behavior in fasted rats (Bagnasco M et al., Regul. Pept. 2003, 111: 161- 167). Repeated icv administration of anti-ghrelin IgG twice daily reduced body weight over five days (Murakami N et al., J. Endocrinol. 2002, 174: 283-288).

A recent study using the peptide antagonist GHS-R 1a, [D-Lys-3] -GHRP-6, showed a decrease in food intake and weight gain in diet-induced obese mice (Asakawa A et al., Gut, 2003, 52: 947- 952). The fact that peptidyl compounds, originally described as stimulators of growth hormone secretion, are able to selectively stimulate food intake in rats without inducing growth hormone secretion, suggests the existence of a GHS-R subtype different from GHS-R1a in the hypothalamus (Torsello A et al., Neuroendocrin. 2000, 72: 327-332; Torsello A et al., Eur. J. Pharmacol. 1998, 360: 123-129).

b) Treatment of lipogenesis, obesity and / or obesity and weight loss (Tschop M et al., Nature 2000, 407: 908-913; Asakawa A et al., Gut 2003, 52: 947-952).

Repeated administration of ghrelin and / or SSHR to freely feeding mice and rats led to an increase in body weight and a decrease in fat utilization (Tschop M et al., Nature 2000, 407: 908-913). Moreover, ghrelin and des-octanoyl ghrelin have been reported to stimulate lipogenesis in vivo (Thompson NM et al., Endocrinol. 2004, 145: 234-242) and inhibit isoproterenol-induced lipolysis in rat adipocytes via atypical GHS-R 1a (Muccioli G et al., Eur. J. Pharmacol. 2004, 498: 27-35). On the other hand, according to available data, the expression of GHS-R 1a in rat adipocytes increases with age or during lipogenesis (Choi K et al., Endocrinol. 2003, 144, 754-759).

c) Treatment of tumor cell proliferation.

As with other participants in the hypothalamic-pituitary axis that regulate growth hormone secretion, there are data for ghrelin and SSHR receptors that show that they can play an important autocrine / paracrine role in some cancers (Jeffery PL et al., Cytokine Growth Factor Rev 2003, 14: 113-122). In the tumor tissues there are specific binding sites of ghrelin, peptidyl and non-peptidyl SSHR. Such tissues include, for example, the PC3 cell line of a prostate tumor (Jeffery PL et al., J. Endocrinology 2002, 172: R7-R11), thyroid tissue (Cassoni P et al., J. Endocrinol. 2000, 165: 139 -146), CALU-1 lung carcinoma cells (Ghe C et al., Endocrinol. 2002, 143: 484-491) and breast (Cassoni P et al., J. Clin. Endocrinol. Metab. 2001, 86: 1738 -1745).

In the case of the mammary gland, specific SSHR binding sites were found in the tumor tissue, which are absent in the normal mammary parenchyma. Synthetic SSHR has been reported to inhibit the proliferation of CALU-1 lung carcinoma cells (Ghe C et al., Endocrinol. 2002, 143: 484-491) and mammary carcinoma cell lines (Cassoni P et al., J. Clin. Endocrinol. Metab . 2001, 86: 1738-1745).

Both ghrelin and non-acylated ghrelin bind to tumor tissues. Since the latter is incapable of contacting GHS-R1a, it is likely that the CCGH binding site in tumor tissues is not GHS-R1a. From the above data, it can be concluded that the binding site in tumor tissues recognizes HGS-R1a ligands, and, in addition, other chemical structures that have not yet been characterized. Thus, HGS-R1a synthetic ligands may have the potential to inhibit the proliferation of tumor cells expressing subgroups of SSHR receptors.

d) Treatment of inflammation / anti-inflammatory effects.

The anti-inflammatory effect of the ghrelin agonist releasing growth hormone peptide-2 (GHRP-2) in chronic arthritis with clinical manifestations of hypermetabolism and cachexia was demonstrated in (Granado M et al., Am. J. Physiol. Endocrinol. Metab. 2005, 288: E486 -492). These data suggest that the anti-inflammatory effect of GHRP-2 is mediated by the activation of ghrelin receptors expressed in immune-competent cells.

e) Treatment of cachexia.

The antikakhetic effect of recombinant growth hormone in animal models (Roubenoff R et al., Arthritis Rheum. 1997, 40 (3): 534-539) was shown in (Ibanez de Caceres I et al., J. Endocrin. 2000, 165 ( 3): 537-544). The data presented are consistent with those obtained in the treatment of patients with rheumatoid arthritis (Roubenoff R et al., J Clin Invest. 1994, 93 (6): 2379-2386).

f) Treatment of gastrectomy (ghrelin replacement therapy)

Stomach hormone ghrelin was given to mice undergoing gastric resection (gastrectomy) or mimicking surgery (Domonville de la Cour C et al., Gut 2005, 54 (7): 907-913). The results show that ghrelin replacement therapy at least partially reverses gastrectomy-induced reduction in body weight and body fat.

g) Treatment of (gastric) postoperative obstruction.

The effect of ghrelin on the motor function of the gastrointestinal tract was studied. It can be shown that ghrelin reverses inhibited gastric evacuation and is a potent prokinetic agent useful in the treatment / management of postoperative gastric obstruction (Trudel L et al., Am J Physiol Gastrointest Liver Physiol 2002, 282 (6): G948-G952).

h) Treatment of diabetes (types I and II).

The effect of ghrelin removal in mice with leptin deficiency has been studied (Sun et al., Cell Metabolism 2006, 3: 379-386). The results show that ghrelin removal enhances insulin secretion in response to glucose. This suggests that inhibition of ghrelin or counteraction of its activity may be one of the possible methods for treating diabetes, including subtypes I and II (see also WO 03/051389).

Other applications include accelerating the recovery process of patients undergoing extensive surgery (eg, US 6194578); acceleration of recovery of patients with burns (for example, US 6194578); attenuation of the protein catabolic response after extensive surgery (e.g., US 6194578); a decrease in cachexia and protein loss after an acute or chronic disease (e.g., US 6194578); treatment of diseases of the central nervous system in patients undergoing medical procedures in conjunction with the use of antidepressants (for example, US 2002/0002137 A1); the acceleration of healing after bone fractures and cartilage growth (for example, US 6194578); treatment or prevention of osteoporosis; stimulation of the immune system; accelerated wound healing (e.g., US 6194578); treatment of growth retardation caused by Prader-Willi syndrome, Turner syndrome and obesity; treatment of intrauterine growth retardation, skeletal dysplasia, hypercortisolism and Cushing's syndrome; treatment of osteochondrodysplasia, Noonan syndrome, schizophrenia, depression and Alzheimer's disease; treatment of pulmonary dysfunction and dependence on the artificial respiration apparatus; treatment of hyperinsulinemia, including nezidioblastoz; auxiliary treatment of ovulation induction; prevention of age-related decline in thymus function; improving muscle strength and mobility (e.g., US 6194578); maintaining the thickness of the skin (for example, 6194578); improved sleep quality (e.g., US 6071926); prophylaxis of congestive heart failure, carried out independently (for example, US 6329342; US 6194578) and in conjunction with the introduction of corticotropin-releasing factor antagonists (for example, US 2001/0041673); metabolic or renal homeostasis (for example, in physically weak elderly people) (for example, US 6194578); improved glycemic control (e.g., US 6251902); treatment of systemic lupus erythematosus and inflammatory bowel disease (e.g., US 2002/0013320); treatment or prevention of physical weakness associated with age or obesity (e.g., US 6194578); as well as stimulation of osteoblasts.

As objects for potential use, animals were not forgotten. Relevant uses include stimulating food intake (Wren AM et al., Diabetes 2001, 50: 2540-2547), stimulating the immune system in small pets, and treating diseases related to aging, stimulating growth in cattle, and also stimulating the growth of wool in sheep. Compounds containing triazole groups are well known in medical chemistry due to their many biological properties. The following patent families are entirely devoted to heterocyclic compounds, which are said to exhibit certain biological activity used for various medical reasons. The triazole groups in the composition of these compounds are indicated explicitly, or they are supposed there. However, none of these patent families mentions either ghrelin-like ligands of the SSHR family of receptors, nor the modulation of these receptors, nor the properties of these substances as stimulators of the secretion of growth hormone GH, and, in general, something like that.

WO 2004/111015 describes glucocorticoid receptor modulators. WO 2004/052280 describes anti-angiogenic compounds and their use as inhibitors of the tyrosine kinase activity of VEGF receptors, as well as their use in cancer. WO 2004/096795 also describes tyrosine kinase inhibitors, preferably C-FMS inhibitors. The publications WO 03/011831 and WO 03/011210 describe heteroaryl heteroalkylamino derivatives and their use as inhibitors of NO synthetase. WO 02/00651 relates to Factor XA inhibitors and their use in thromboembolic disorders. WO 01/94318 and WO 01/94317 describe chemical libraries of substituted azole derivatives and methods for their synthesis for subsequent use in high-speed screening for the development of new drugs. However, no biological activity or medical use of the compounds is mentioned there, nor are specific compounds indicated. WO 00/76971 and WO 00/76970 are devoted to serine protease inhibitors useful as antithrombolytic agents. WO 01/36395 describes the use of triazole derivatives as farnesyl transferase inhibitors. WO 96/33176 and US 5,703,092 relate to hydroxamic acid compounds and their use as metal oprotease and TNF inhibitors. WO 93/09095 describes 2-heterocyclylethylamine derivatives and their use in the treatment of neurological and neurodegenerative disorders. Compounds for the treatment of thrombosis, in particular Xla Factor inhibitors, are disclosed in WO 2004/103270. WO 98/38177, US 6506782, US 6849650 and US 2003/0130188 describe the use of heterocyclic compounds as inhibitors of the release of amyloid beta peptide or the synthesis of such compounds, followed by use in Alzheimer's disease.

Heterocyclic compounds that may be useful as SSHR are also described in the literature.

For example, WO 00/54729 describes the use of heterocyclic aromatic compounds as stimulators of growth hormone secretion. It is said that they stimulate endogenous production and / or release of GH and may also contain triazole groups. In addition, a method is described for increasing the content of endogenous GH or endogenous production or release of GH, comprising administering such an SSHR. Moreover, a method for preventing or treating osteoporosis (strengthening bone density and / or bone strength), or treating obesity, or increasing muscle mass and / or muscle strength and function in the elderly, or treating or preventing physical weakness in the elderly, including the introduction of such a SSGR.

However, despite the indication of GH release in vivo, publication WO 00/54729 is not in fact able to confirm such an effect. Neither in vitro nor in vivo data are presented that would demonstrate any stimulation or enhancement of endogenous production and / or release of GH.

In addition, the publication WO 00/54729 does not describe or show the effect of these claimed compounds on any biological target, that is, there is no evidence confirming that the claimed compounds are ligands of one or more specific receptors, for example, a family of receptors that bind would modulate their activity with them.

In addition, in the publication WO 00/54729 not described and not shown inhibitory and / or antagonistic activity of the claimed compounds. Essentially, it is not shown that such compounds reduce the content of endogenous GH and / or inhibit or reduce the endogenous production and / or release of GH. The inhibitory effect of the compounds on any of the receptors mentioned is also not demonstrated.

Patents US 6525203, US 6518292, US 6660760 are part of one patent family published in WO 00/54729, in which, however, triazole groups are not mentioned once in the features of the claims. Regarding biological activity, the above facts apply to the entire WO 00/54729 family.

WO 2004/021984 describes heterocyclic aromatic compounds of the GH secretagogue and says that they are useful in stimulating endogenous production or release of GH. However, the claimed compounds contain bi-tetracyclic aromatic conjugated systems and do not contain triazole groups.

As in the case of WO 00/54729, in vivo GH release is indicated, but neither in vivo nor in vitro data are presented that would demonstrate any stimulation or enhancement of endogenous GH production and / or release. As for biological activity, the statements made with respect to WO 00/54729 are also applicable here.

Publication WO 97/23508 describes peptidomimetic compounds, such as SSHR, and says that they act directly on pituitary cells in vitro to release GH from them, and also demonstrate improved properties, such as increased resistance to proteolytic degradation and improved bioavailability. In addition, the claimed compounds can be administered in vivo, and the release of GH is enhanced. The compounds are peptide derivatives, it is not explicitly stated that they contain triazole groups.

However, as in the case of the above WO 00/54729 and WO 2004/021984, the publication WO 97/23508 does not show any in vitro or in vivo data confirming the claimed effects, such as direct effects on the hypothalamus cells, release from them GH and improved properties. Moreover, with respect to biological targets and inhibitory / antagonistic activity, the statements made previously for WO 00/54729 are applicable.

Patents US 6127391, US 5977178 and US 6555570 are part of one patent family WO 97/23508. The same statements apply to them as for WO 97/23508.

Disclosure of invention

The present invention is the search for new compounds that can be used to treat physiological and / or pathophysiological conditions in mammals, especially in humans, mediated by SSHR receptors. Another objective is the search for compounds for the above treatment, and treatment should be carried out by modulating the activity of the SSHR receptors. Another objective is the search for antagonists of SSHR receptors for such treatment. Another objective is the search for SSHR receptor agonists for such treatment.

Thus, the present invention is directed to the use of a compound corresponding to formula (I)

Where

R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, arylalkylalkylalkylalkyl, alkyl heteroarylalkyl, heterocyclyl and / or heterocyclylalkyl may contain up to 3 substituents independently selected from the group consisting of halogen, —F, —Cl,

-Br, -I1 -N ₃ , -CN, -NR7R8, -OH, -NO ₂ , alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl; and is preferably selected from the group consisting of alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, optionally containing up to 3 substituents independently selected from the group consisting of halogen, —F, —Cl, —Br, —I, —N ₃ , —CN, -NR7R8, -OH, -NO ₂ , alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl;

R _{2 is} selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, aryl, aryl, alkyl heterocyclyl, and / or heterocyclylalkyl, which may contain up to 3 landlords independently selected from the group consisting of halogen, —F, —Cl, —Br, —I, —N ₃ , —CN, —NR7R8, —OH, —NO ₂ alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl; and is preferably selected from the group consisting of alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, optionally containing up to 3 substituents independently selected from the group consisting of halogen, —F, —Cl, —Br, —I, —N ₃ , —CN, -NR7R8, -OH, -NO ₂ , alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl;

one of the radicals R3 and R4 represents a hydrogen atom, and the other radical is selected from the group consisting of hydrogen atom, alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -alkyl-O-aryl, -alkyl-O-arylalkyl, - alkyl-O-heteroaryl, -alkyl-O-heteroarylalkyl, -alkyl-O-heterocyclyl, alkyl-O-heterocyclylalkyl, -alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, - alkyl -CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, -alkyl-CO-heterocyclylalkyl, -alkyl-C (O) O-aryl, -alkyl-C (O) O-arylalkyl,

-alkyl-C (O) O-heteroaryl, -alkyl-C (O) O-heteroarylalkyl, -alkyl-C (O) O-heterocyclyl, -alkyl-C (O) O-heterocyclylalkyl, -alkyl-CO-NH ₂ , -alkyl-CO-OH, -alkyl-NH ₂ , -alkyl-NH-C (NH) -NH ₂ , alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, alkyl-S-alkyl, alkyl-SH, wherein aryl, heteroaryl, arylalkyl , heteroarylalkyl, heterocyclyl and / or heterocyclylalkyl may contain up to 3 substituents independently selected from the group consisting of halogen, —F, —Cl, —Br, —I, —N ₃ , —CN, —NR7R8, —OH, —NO ₂ alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl; and is preferably selected from the group consisting of "arylalkyl, heteroarylalkyl, heterocyclylalkyl, alkyl-O-aryl, -alkyl-O-arylalkyl, -alkyl-O-heteroaryl, -alkyl-O-heteroarylalkyl, -alkyl-O-heterocyclyl, alkyl -O-heterocyclylalkyl, -alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, alkyl-CO-heterocyclylalkyl, -alkyl-C (O) O-aryl, - alkyl-C (O) O-arylalkyl, - alkyl-C (O) O-heteroaryl, -alkyl-C (O) O-heteroarylalkyl, -alkyl-C (O) O- heterocyclyl , -alkyl-C (O) O-heterocyclylalkyl, -alkyl-CO-NH ₂ , -alkyl-CO-OH, -alkyl-NH ₂ , - alkyl-NH — C (NH) —NH ₂ , wherein aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and / or heterocyclylalkyl may contain up to three substituents independently selected from the group consisting of halogen, —F, —Cl, —Br, - I, —N ₃ , —CN, —NR7R8, —OH, —NO ₂ , alkyl, aryl, arylalkyl, —O-alkyl, —O-aryl, —O-arylalkyl;

R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -CO-alkyl, -CO-cycloalkyl, -CO-cycloalkylalkyl, -CO-aryl, arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-heterocyclylalkyl, CO-C * (R9R10) -NH ₂ , -CO-CH ₂ -C * (R9R10) -NH ₂ , -CO —C * (R9R10) —CH ₂ —NH ₂ , alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, which may contain up to 3 substituents independently selected from the group consisting of halogen, —F, —Cl, —Br, —I, —N ₃ , —CN, —NR7R8, —OH, —NO ₂ , alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl "; and is preferably selected from the group consisting of hydrogen, -CO-alkyl, -CO-cycloalkyl, -CO-aryl, -CO-heteroaryl, -CO-arylalkyl , - CO-heteroarylalkyl, -CO-heterocyclyl, -CO-C * (R9R10) -NH ₂ , -CO-CH ₂ -C * (R9R10) -NH ₂ , -CO-C * (R9R10) -CH ₂ - NH ₂ which may contain up to 3 substituents independently selected from the group consisting of halogen, —F, —Cl, —Br, —I, —N ₃ , —CN, —NR7R8, —OH, —NO ₂ , alkyl, aryl arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl;

R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, and is preferably a hydrogen atom;

R7 and R8 are independently selected from the group comprising a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, and preferably represent a hydrogen atom;

R9 and R10 are independently selected from the group consisting of hydrogen atom, alkyl, side chain of natural alpha amino acids, side chain of unnatural alpha amino acids, and, preferably, selected from the group comprising hydrogen atom and alkyl;

m corresponds to 0, 1 or 2, and preferably 0; and

* means a carbon atom in the R or S configuration, if it is chiral; for the manufacture of a medicament for the treatment or prevention of physiological and / or pathophysiological conditions selected from the group including short-term, medium-term and / or long-term regulation of energy balance; short-term, medium-term and / or long-term regulation (stimulation and / or inhibition) of food intake; adipogenesis, obesity and / or obesity; an increase and / or decrease in body weight in mammals, mediated by SSHR receptors, the treatment being carried out by modulating SSHR receptors, and the compound is an antagonist of SSHR receptors.

The invention is also directed to the use of a compound of formula (I), wherein

R4 represents a hydrogen atom;

R5 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, aryloalkylsulfonyl, -CO-acyloalkyl, -CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-heterocyclylalkyl;

moreover, if R5 is —CO-heteroarylalkyl, then heteroaryl is not imidazole;

and, if R5 is —CO-heterocyclyl, the heterocyclyl contains only nitrogen atoms as hetero atoms and at least two nitrogen atoms are included in the heterocyclyl;

and, if R5 is -CO-heterocyclylalkyl, the heterocyclyl contains only nitrogen atoms as heteroatoms, and if one or two nitrogen atoms enter the heterocyclyl, then the nitrogen atoms are not in position 1 of the heterocyclyl through which the heterocyclyl directly binds to the carbonyl group - CO-;

and where alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, -CO-cycloalkyl, -CO-cycloalkyl-alkyl-alkyl , -CO-heteroarylalkyl, -CO-heterocyclyl, and / or -CO-heterocyclylalkyl may contain up to 3 substituents independently selected from the group consisting of halogen, -F, -Cl, -Br, -I, -N ₃ , -CN , -NR7R8, -OH, -NO ₂ , alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl;

moreover, if R5 is —CO-cycloalkyl or —CO-cycloalkylalkyl, then R5 is not substituted with NR7R8 at position 1 of cycloalkyl in which the C atom directly binds cycloalkyl to the carbonyl group —CO— if R5 is —CO-cycloalkyl, or alkyl, if R5 is —CO-cycloalkylalkyl; and

if R5 is —CO-aryl or —CO-arylalkyl, and aryl is phenyl / benzene and contains only one substituent, then this substituent cannot be —NR7R8;

R6 represents a hydrogen atom;

R7 and R8 are independently selected from the group consisting of a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, and preferably represent a hydrogen atom; and

m = 0, 1 or 2, more preferably 0

for the manufacture of a medicament for the treatment or prevention of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors, said treatment being carried out by modulating SSHR receptors, and the compound is an agonist of SSHR receptors.

In another aspect, the invention is directed to the use of a compound of formula (I), wherein R1 is selected from the group consisting of hydrogen, methyl, (2-methoxyphenyl) methyl, (3-methoxyphenyl) methyl, (4-methoxyphenyl) methyl, (3 methoxyphenyl) ethyl, (4-methoxyphenyl) ethyl, phenyl, phenyl methyl, phenyl ethyl, (4-ethyl phenyl) methyl, (4-methyl phenyl) methyl, (4-fluorophenyl) methyl, (4 -bromophenyl) methyl, (2,4-dimethoxyphenyl) methyl, (3,5-dimethoxyphenyl) methyl, 2,2-diphenyl-ethyl, naphthalen-1-yl-methyl, 1H-indol-3-yl- methyl, 2- (1H-indol-3-yl) -ethyl, 3- (1H-indol-3-yl) -propyl, 4-methyl-phenyl, 4-ethyl-phenyl, n-hexyl, (3,4 dichlorophenyl) -methyl, (4-nitro-phenyl) -methyl, (pyridin-2-yl) -methyl, (pyridin-3-yl) -methyl, (pyridin-4-yl) -methyl, (thiophen-2-yl) methyl, (thiophen-3-yl) methyl, (furan-2-yl) methyl, (furan-3-yl) methyl;

R2 is selected from the group consisting of methyl, 1H-indol-3-yl-methyl, 2- (1H-indol-3-yl) -ethyl, 3- (1H-indol-3-yl) -propyl, 2-phenyl- ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 2-methoxy-phenylmethyl, 3-methoxy-phenylmethyl, 4-methoxy-phenylmethyl, 2-methoxy-phenylethyl, 3-methoxy-phenylethyl, 4-methoxy-phenylethyl;

R3 is selected from the group consisting of hydrogen, methyl, propan-2-yl, 2-methyl-propan-1-yl, butan-2-yl, butan-1-yl, -CH ₂ -SH, - (CH ₂ ) _2- S-CH ₃ , 1H-indol-3-yl-methyl, phenyl-methyl, 2-phenyl-ethyl, -CH ₂ -O-CH ₂ -phenyl, -CH ₂ -CO-CH ₂ -phenyl, - (CH ₂ ) ₂ -CO-CH ₂ -phenyl, -CH ₂ -C (O) O-phenyl, - (CH ₂ ) ₂ -C (O) O-phenyl, hydroxymethyl, 1-hydroxyethan-1-yl, -CH ₂ -CO-NH ₂ , - (CH ₂ ) ₂ -CO-NH ₂ , (1-hydroxy-benzene-4-yl) methyl, -CH ₂ -CO-OH, - (CH ₂ ) ₂ - CO-OH, - (CH ₂ ) 4-NH ₂ , (1H-imidazol-5-yl) methyl, - (CH ₂ ) ₃ -NH-C (NH) -NH ₂ , - (CH ₂ ) ₃ - NH ₂ , - (CH ₂ ) ₃ —NH — CO — NH ₂ , and is preferably selected from the group consisting of 1H-indol-3-yl-methyl, —CH ₂ —CO — CH ₂ phenyl, - (CH ₂ ) ₂ -CO-CH ₂ -phenyl, -CH ₂ - C (O) O-phenyl; - (CH ₂ ) ₂ -C (O) O-phenyl;

R4 represents a hydrogen atom;

R5 is selected from the group consisting of a hydrogen atom, —CO — CH ₂ —NH ₂ (residue Gl), —CO — CH ₂ —CH ₂ —NH ₂ (residue beta-Ala), —CO — CHCH ₃ —NH ₂ (residue D- and / or L-alpha-Ala), -CO- (pyrrolidin-2-yl) (residue D- and / or L-Pro), 2-amino-2-carbonyl-propane (residue 2-amino-isobutyric acids / Aib), 4-carbonyl-1H-piperidine, 3-carbonyl-1H-piperidine, R- (3-carbonyl-1H-piperidia), S- (3-carbonyl-1H-piperidia), 2-carbonyl-1H piperidine, R- (2-carbonyl-1H-piperidine), S- (2-carbonyl-1H-piperidine), 1-amino-2-carbonyl-benzene, carbonyl-cyclohexane, 2-acetyl-pyridine, 3-acetyl -pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine, 3-propionyl-pyridine , 4-propionyl-pyridine, (R-1-amino) -2-carbonyl-cyclohexane, (S-1-amino) -2-carbonyl-cyclohexane, 2-carbonyl-1H-imidazole, 2-carbonyl-pyridine, 3 -carbonyl-pyridine, 4-carbonyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-pyrazine, 2-carbonyl-4-hydroxy-1H-pyrrolidine, 4-carbonyl-1H, 3H-diazacyclohexane, methyl -sulfonyl, phenylsulfonyl, 1-carbonyl-1-amino-2-phenylethane, phenylmethyl, 1-carbonyl-4-azide-benzene, 2-carbonyl-2,5-dihydro-1H-pyrrole, 2-carbonyl-piperazine, 2 -carbonyl-1H-pyrrolidine, 2-aminoethane, carbonyl-benzene, 2-carbonyl-pyrazine, 3-carbonyl-pyrazine, 4-carbonyl-oxacyclohek en, 4-methyl- phenylsulfonyl, phenylmethyl-sulfonyl;

R6 represents a hydrogen atom;

and m = 0

for the manufacture of a medicament for the treatment or prevention of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors, said treatment being carried out by modulating SSHR receptors, and the compound is an agonist of SSHR receptors.

In accordance with one aspect of the invention, the SSHR receptors are selected from the group consisting of SSHR, type 1 GHS receptors, GHS-R 1a, GHS-R 1b, motilin receptor, motilin receptor 1a, neurotensin receptor, TRH receptor, GPR38 (FM1 ), GPR39 (FM2), FM3, a subtype of GHS-R, GHS-binding site (or CCGR-binding site), GHS-R of the heart muscle, GHS-R of the mammary gland, preferably selected from the group including CCGR, type 1 receptors, GHS-R 1a, GHS-R 1b, and most preferably GHS-R 1a.

According to the invention, physiological and / or pathophysiological conditions are acute fatigue and loss of muscle mass after selective surgery, adipogenesis, obesity, age-related weakening of the thymus function, age-related functional deviation in the elderly, age-related deviations in domestic animals, Alzheimer's disease, anorexia ( for example, associated with cachexia or aging); anxiety, low blood pressure, decrease / increase in body weight, restoration of bones after fractures (acceleration of the process), stimulation of bone remodeling, cachexia and loss of proteins due to chronic diseases such as cancer or AIDS, dysfunctions of the cardiovascular system (e.g. associated with valve disease, myocardial infarction, cardiac muscle hypertrophy or congestive heart failure), cardiomyopathy, stimulation of cartilage growth, catabolic disorders associated with pulmonary dysfunction and dependence on the mechanical ventilation system, catabolic side effects of glucocorticoid use, catabolic state of aging, central nervous system disorders (together with antidepressants), chronic dialysis, chronic fatigue syndrome, improved cognitive function (for example, with dementia or Alzheimer's disease), complicated fractures (e.g., osteogenesis disorders) associated with transplantation complications, congestive heart failure (can be treated in conjunction with an antagonist and corticotropin-releasing factor), Crohn’s disease and ulcerative colitis, Cushing's syndrome, dementia, depression, short-term, medium-term and / or long-term regulation of energy balance, short-term, medium-term and / or long-term regulation of food intake (stimulation and / or inhibition), fragility bones (e.g., in the elderly), gastrectomy (ghrelin replacement therapy), gastric postoperative obstruction, improved glycemic control, stimulation of the release of growth hormone in the elderly, hormone replacement growth in stressed patients, growth stimulation in livestock, growth retardation associated with Prader-Willi syndrome and Turner syndrome, growth retardation due to Crohn's disease, growth retardation, hair / nail growth support, hip fractures, hunger, hypercortisolism , hyperinsulinemia, including nezidioblastosis, hypothermia, immune deficiency in people with a reduced T4 / T8 cell ratio, improved immune response during vaccination, stimulation of the immune system in pets, stimulation immune system suppression, immune system suppression in patients with such suppression, inflammation or inflammatory effects, intestinal inflammation, insulin resistance in the heart, insulin resistance in patients with type 2 diabetes, insulin resistance, including type II diabetes (NIDDM - non- insulin-dependent diabetes mellitus), diabetes, type 1 diabetes, type 2 diabetes, intrauterine growth retardation, irritable bowel syndrome, lipodystrophy (e.g., HIV-induced), maintenance of metabolic homeostasis, increased milk yield cattle, increase muscle mass / strength, improve muscle mobility, increase muscle strength, maintain muscle strength / functioning in the elderly, muscle atrophy, musculoskeletal disorders (e.g. in the elderly), Noonan syndrome, obesity and its associated slowdown growth, stimulation of osteoblasts, osteochondrodysplasia, osteoporosis, induction of ovulation (auxiliary treatment), physiological short stature, including growth hormone deficiency in children, postoperative obstruction, weakening of protein catab response after extensive surgery or trauma, increased activity of protein kinase B, psychosocial deprivation syndrome, pulmonary dysfunction and dependence on mechanical ventilation devices, improved lung function, pulsating induction of growth hormone secretion, treatment of burns, and reduced hospitalization time for patients with burns (acceleration healing), renal failure caused by stunted growth, maintenance of renal homeostasis and the elderly with increased fragility of the body addition, sarcopenia, schizophrenia, maintenance of sensory function (e.g., hearing, vision, smell and taste), short bowel syndrome associated with a short disease of small stature, skeletal dysplasia, maintaining skin thickness, sleep disturbances, improving sleep quality, thrombocytopenia, stimulating development thymus, restoration or growing of teeth, proliferation of tumor cells, ventricular dysfunction or cases of reperfusion, AIDS-related exhaustion, exhaustion due to chronic liver disease, exhaustion in connection with chronic obstructive pulmonary disease, wasting, associated with multiple sclerosis or other neurodegenerative diseases, cachexia, induced fractures, wool growth stimulation in sheep, acceleration of wound healing and / or delayed wound healing.

In yet another aspect, physiological and / or pathophysiological conditions are stunted growth, cachexia, short-term, medium-term, and / or long-term regulation of energy balance; short-term, medium-term and / or long-term regulation (stimulation and / or inhibition) of food intake; adipogenesis, obesity and / or obesity; increase and / or decrease in body weight; diabetes, type 1 diabetes, type 2 diabetes, tumor cell proliferation; inflammation, effects of inflammation, gastric postoperative obstruction, postoperative obstruction and / or gastrectomy (ghrelin-replacement therapy).

JMV2951, a ghrelin receptor agonist, has been shown to stimulate food intake and secretion of growth hormone in rats. The indicated pharmacological action can be used to treat growth retardation and cachexia (data were presented in the form of a poster at a meeting of the Endocrinological Society in 2007).

It was also shown that JMV2959 and JMV3002 (ghrelin receptor antagonists) reduce food intake without modifying the secretion of growth hormone in rats. In addition, JMV2959 and JMV2810 reduced body weight and body fat in animal-induced diet-induced obesity models. These data substantiate the applicability of antagonists and inverse agonists of the ghrelin receptor for the treatment of obesity and concomitant metabolic disorders. The data presented below were part of the posters presented at the meeting of the Endocrinological Society in 2007 and 2008.

The inhibitory effect of JMV2959 and JMV3002 on food intake in rats was confirmed by a group of Dr. S. Dickson who published their data (Salome N et. Al. Eur J Pharmacol 2009; 612: 167-173.

The following substances are mentioned above:

JMV2959 (substance 50 according to the invention)

A medicament in accordance with one aspect of the invention comprises at least one additional pharmacologically active substance, which is a CCGR receptor antagonist and an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant [1H-pyrazole-3-carboxamide,

5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methyl-N-1-piperidinyl-, monohydrochloride].

It is known that there is an interaction between the endocannabioid and ghrelin systems for controlling food intake and energy balance. It has been shown that stimulation of food intake with ghrelin is suppressed by the endocannabio receptor antagonist rimonabant (Tucci S et al, British Jourmal of Pharmacology 2004, 143: 520-523; Kola B et al., PloS One 2008, 3: e1797, 1-8.) The simultaneous administration of an endocannabioid receptor antagonist and a ghrelin receptor antagonist will affect the regulation of energy balance at two different levels and is more effective in terms of control food intake and weight gain than the introduction of these agents separately.

The medicament according to the invention can be applied before, during and / or after treatment with at least one additional pharmacologically active substance.

One aspect of the invention is the use of a medicament that contains a CCGR receptor antagonist, and the additional pharmacologically active substance is an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant [1H-pyrazole-3-carboxamide, 5- ( 4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methyl-N-1-piperidinyl-, monohydrochloride].

The invention also encompasses triazole compounds selected from the group consisting of

Compound 1

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 2

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 3

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 4

(R) -N- (1- (5-benzyl-4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 5

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 6

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 7

(R) -N- (1- (4- (3-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 8

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 9

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 10

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 11

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 12

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 13

(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 14

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-bromobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 15

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 16

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 17

(R) -N- (1- (4,5-bis (2- (1H-indol-3-yl) ethyl) -4H-1,2,4-triazol-3-yl) -2- (1H- indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 18

(S) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1 ₁ 2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 19

(R) -N- (1- (4- (3-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 20

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 21

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3 ₎ 5-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 22

(R) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-2-methylpropanamide,

Compound 23

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 24

(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5- (3- (1H-indol-3-yl) propyl) -4H-1,2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 25

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2-methoxy) benzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 26

(R) -N- (1- (4- (2-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 27

(R) -N- (2- (1H-indol-3-yl) -1- (4- (naphthalen-1-ylmethyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 28

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3,4-dichlorobenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 29

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-fluorobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 30

(R) -N- (1- (4- (4-fluorobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 31

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) piperidin-4-carboxamide,

Compound 32

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3- il) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide,

Compound 33

(R) -N- (1- (4- (4-methylbenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-amino-2-methylpropanamide,

Compound 34

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methylbenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 36

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) piperidin-2-carboxamide,

Compound 37

(R) -N- (1- (4- (4-methylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 38

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide,

Compound 39

(R) -N- (1- (5-benzyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 40

(2S, 4R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole- 3-yl) ethyl) -4-hydroxypyrrolidin-2-carboxamide,

Compound 41

(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-3-carboxamide,

Compound 42

(R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) piperidine-3-carboxamide,

Compound 43

(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 44

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

Compound 45

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) piperidin-4-carboxamide,

Compound 46

(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) pyrrolidin-2-carboxamide,

Compound 47

(R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) pyrrolidin-2-carboxamide,

Compound 48

(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-2-carboxamide,

Compound 49

(R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-2-carboxamide,

Compound 50

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

Compound 51

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

Compound 52

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-4-yl) acetamide,

Compound 53

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) cyclohexanecarboxamide,

Compound 54

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) piperidin-4-carboxamide,

Compound 55

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) piperidin-3-carboxamide,

Compound 56

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3-aminopropanamide,

Compound 57

(5) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-aminopropanamide,

Compound 58

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide,

Compound 59

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3- (pyridin-3-yl) propanamide,

Compound 60

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

Compound 61

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

Compound 62

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

Compound 63

(R) -N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole- 3-yl) ethyl) piperidin-2-carboxamide,

Compound 64

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

Compound 65

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,

Compound 66

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,

Compound 67

(R) -N-1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl ) piperazine-2-carboxamide,

Compound 68

(S) -N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole- 3-yl) ethyl) pyrrolidin-2-carboxamide,

Compound 69

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

Compound 70

(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazole -3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,

Compound 71

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) pyrazin-2-carboxamide,

Compound 72

(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide,

Compound 73

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) picolinamide,

Compound 74

(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl l) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethanamine,

Compound 75

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

Compound 76

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,

Compound 77

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,

Compound 78

(R) -N-1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine -2-carboxamide,

Compound 79

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide

Compound 80

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) picolinamide,

Compound 81

(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) ethyl) piperazin-2-carboxamide,

Compound 82

(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

Compound 83

(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

Compound 84

(R) -N-1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine -2-carboxamide,

Compound 85

(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,

Compound 86

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-cis-aminocyclohexanecarboxamide,

Compound 87

(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) piperidin-3-carboxamide,

Compound 88

(R) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide,

Compound 89

(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,

Compound 90

(R) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,

Compound 91

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

Compound 92

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-bromobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 93

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2-phenylethyl) -2-amino-2-methylpropanamide,

Compound 94

(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (thiophen-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) piperidine-4-carboxamide,

Compound 95

(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,

Compound 96

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4-methyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole -3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 97

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-methyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 98

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl ) ethyl) -2-amino-2-methylpropanamide,

Compound 99

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 100

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-methyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 101

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 102

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 103

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 104

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole -3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 105

(R) -N- (1- (5-benzyl-4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide,

Compound 106

(R) -N- (1- (5-benzyl-4- (2,2-diphenylethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 107

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,2-diphenylethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 108

(R) -N- (1- (4- (3,5-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 109

(R) -N- (1- (4,5-dibenzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2 methylpropanamide

Compound 110

(R) -N- (1- (5-benzyl-4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide,

Compound 111

(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 112

(S) -N- (1- (4- (2,4-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 113

(R) -N- (1- (4- (3,5-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 114

(R) -N- (1- (4- (4-bromobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 115

(R) -N- (1- (4- (2-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 116

(S) -N- (1- (4- (2 _| 4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 117

(R) -N- (1- (4,5-diphenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2 methylpropanamide

Compound 118

(R) -N- (1- (4- (3,4-dichlorobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 119

(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) ethanamine,

Compound 120

(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide,

Compound 121

(R) -N- (1- (4- (4-fluorobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 122

(R) -N- (1- (4- (3,4-dichlorobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 124

(R) -N- (1- (4- (4-methylbenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 125

(S) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-2-methylpropanamide,

Compound 126

(S) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 128

N - ((R) -1- (4- (4-nitrobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 129

(S) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 130

(R) -N- (1- (4- (4-methoxyphenethyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 131

(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (thiophen-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 132

(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 133

(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) piperidine-3-carboxamide,

Compound 135

(S) -N - ((B) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) pyrrolidin-2-carboxamide,

Compound 135

N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

Compound 136

N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2- (pyridn-4-yl) acetamide,

Compound 137

(2R) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-2-carboxamide,

Compound 138

N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide

Compound 139

N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminopyridine-3-carboxamide,

Compound 140

(2S) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-aminopropanamide,

Compound 141

N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,

Compound 142

N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) piperidin-4- carboxamide

Compound 143

(2S) -N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) pyrrolidine-2-carboxamide,

Compound 144

N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) -2-aminoacetamide ,

Compound 145

N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) -2- ( pyridin-2-yl) acetamide,

Compound 146

N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) picolinamide,

Compound 147

N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) picolinamide,

Compound 148

N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

Compound 149

N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

Compound 150

(2S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,

Compound 152

N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

Compound 153

N - ((R) -1- (4- (4-methoxybenzyl) -5-phenzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-trans-aminocyclohexanecarboxamide,

Compound 154

N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide,

Compound 155

(3S) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-3-carboxamide,

Compound 156

N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide,

Compound 157

N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) picolinamide,

Compound 158

N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) piperidin-4-carboxamide,

Compound 159

N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2 ₎ 4-triazol-3-yl) ztyl) picolinamide,

Compound 160

N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

Compound 161

N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) pyrazine-2-carboxamide,

Compound 162

N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) -2-aminoacetamide,

Compound 163

N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) piperidine-4-carboxamide,

Compound 164

N - ((R) -1- (5-benzyl-4 - ((pyridin-2-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) picolinamide,

Compound 165

N - ((R) -1- (5-benzyl-4 - ((pyridin-2-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-acetamide,

Compound 166

N - ((R) -1- (5-benzyl-4 - ((pyridin-2-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) piperidine-4-carboxamide,

Compound 167

N - ((R) -1- (5-benzyl-4 - ((pyridin-4-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,

Compound 168

N - ((R) -1- (5- (4-methoxybenzyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 169

N - ((R) -1- (5-benzyl-4 - ((pyridin-4-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) picolinamide,

Compound 170

N - ((R) -1- (5-benzyl-4 - ((pyridin-4-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) 2-amino-acetamide,

Compound 171

(R) -benzyl-3- (2-aminoisobutyramido) -3- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4- triazol-3-yl) propanoate,

Compound 172

N - ((R) -1- (5-benzyl-4 - ((pyridin-3-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,

Compound 173

N - ((R) -1- (4-benzyl-5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide,

Compound 174

N - ((R) -2- (1H-indol-3-yl) -1- (4-methyl-5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) picolinamide,

Compound 175

N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 176

N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) benzamide,

Compound 177

(R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) -1N- phenylmethanesulfonylamine,

Compound 178

(R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) -N- tosilethanamine,

Compound 179

N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 180

N-1 - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) ethane-1,2-diamine,

Compound 181

N - ((R) -1- (4 - ((furan-2-yl) methyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,

Compound 182

N - ((R) -1- (4 - ((furan-2-yl) methyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) picolinamide,

Compound 183

N - ((R) -1- (4 - ((furan-2-yl) methyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) piperidine-4-carboxamide,

Compound 184

N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) tetrahydro-2H-pyran-4-carboxamide,

Compound 185

N - ((R) -1- (5 - ((1H-indol-3-yl) methyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 186

(2S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-amino-3-phenylpropanamide,

Compound 187

(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) -N-tosilethanamine,

Compound 188

N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -4-azidobenzamide,

Compound 189

N-benzyl- (R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl ) ethanamine,

Compound 190

(2S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) -2,5-dihydro-1H-pyrrole-2-carboxamide.

The invention also includes pharmaceutical compositions containing at least one thiazole compound in a pharmacologically active amount. The active ingredient is present in a unit dose of 0.001 to 100 mg per kg of patient body weight.

The pharmaceutical composition may further comprise at least one pharmaceutically acceptable carrier and / or excipient and at least one additional pharmacologically active substance, which is an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant [1H-pyrazole-3 carboxamide

5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methyl-N-1-piperidinyl-, monohydrochloride].

Brief Description of the Drawings

Figure 1-13 shows graphs of competitive binding obtained by analysis of the binding of GHS-R 1A receptor-ligand using ¹²⁵ I-His ⁹ -hrelin and selected compounds 9, 31, 39, 45, 50, 62, 64, 71 , 73, 74, 79, 81, and 90, as described in subsection II) of the examples section.

Figures 14-40 show calculated dose-response curves for in vitro analysis of intracellular calcium release using CHO cells transfected with human GHS-R 1a, as well as selected compounds 1, 9, 12, 20, 22, 31, 39, 41, 42, 45, 46, 47, 48, 49, 50, 51, 55, 62, 64, 67, 71, 73, 74, 79, 81, 90 and ghrelin, as described in subsection III) of the examples section, and also the values of EC ₅₀ and K _I for agonists of the SSHR receptor and IC ₅₀ and K _I for antagonists of the SSHR receptor.

Figures 41-46 show the effects of selected compounds 9, 38, 50, 64, 74, 81 on the inhibition curves of isoproprenol-induced lipolysis of unacylated ghrelin in primary mouse adipocytes under diet-induced obesity conditions, as described in section VIII) of the examples section.

The implementation of the invention

In accordance with the invention were obtained compounds whose structure corresponds to the formula (I)

Where

R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylalkylalkylalkylalkylalkyl aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and / or heterocyclylalkyl may contain up to 3 substituents independently selected from the following group: "halogen, -F, -Cl, -Br, -I, -N ₃ , -CN, -NR ₇ R ₈ , —OH, —NO ₂ , alkyl, aryl, arylalkyl, —O-alkyl, —O-aryl, —O arylalkyl "; and preferably, if they are selected from the group "alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl", possibly these residues contain up to 3 substituents independently selected from the following group: "halogen, -F, -Cl, -Br, -I, "-N ₃ , -CN, -NR7R8, -OH, -NO ₂ , alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl";

One of the radicals R3 and R4 represents a hydrogen atom, and the other is selected from the following group: "hydrogen atom, alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -alkyl-O-aryl, -alkyl-O-arylalkyl, - alkyl-O-heteroaryl, -alkyl-O-heteroarylalkyl, -alkyl-O-heterocyclyl, alkyl-O-heterocyclylalkyl, -alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, - alkyl -CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, -alkyl-CO-heterocyclylalkyl, -alkyl-C (O) O-aryl, -alkyl-C (O) O-arylalkyl, -alkyl-C (O) O- heteroaryl, -alkyl-C (O) O-heteroarylalk l, -alkyl-C (O) O-heterocyclyl, -alkyl-C (O) O- heterocyclylalkyl, _{-alkyl-CO-NH2,} -alkyl-CO-OH, _-alkyl-NH2, -alkyl-NH- C (NH) -NH ₂ , alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, alkyl-S-alkyl, alkyl-SH ", wherein aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and / or heterocyclylalkyl may contain up to 3 substituents independently selected : "halogen, -F, -Cl, -Br, -I, -N ₃ , -CN, -NR7R8, -OH, -NO ₂ , alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, - O-arylalkyl "; and preferably, if selected from the group “arylalkyl, heteroarylalkyl, heterocyclylalkyl, -alkyl-O-aryl, -alkyl-O-arylalkyl, -alkyl-O-heteroaryl, -alkyl-O-heteroarylalkyl, -alkyl-O-heterocyclyl, alkyl-O-heterocyclylalkyl, -alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, alkyl-CO-heterocyclylalkyl, -alkyl- C (O) O-aryl, -alkyl-C (O) O-arylalkyl, -alkyl-C (O) O-heteroaryl, -alkyl-C (O) O-heteroarylalkyl, -alkyl-C (O) O- heterocyclyl, -alkyl-C (O) O-heterocyclylalkyl, -alkyl-CO-NH ₂ , -alkyl-CO-OH, -alkyl-NH ₂ , -alkyl-NH -C (NH) -NH ₂ , "wherein aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and / or heterocyclylalkyl may contain up to three substituents independently selected from the following group:" halogen, -F, -Cl, -Br, -I , —N ₃ , —CN, —NR7R8, —OH, —NO ₂ , alkyl, aryl, arylalkyl, —O-alkyl, —O-aryl, —O-arylalkyl ";

R5 is selected from the group consisting of "hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -CO-alkyl, -CO-cycloalkyl, -CO-cycloalkylalkyl, -CO-aryl,

-CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-heterocyclylalkyl, -CO-C * (R9R10) -NH ₂ , -CO-CH ₂ -C * (R9R10) -NH ₂ , -CO-C (R9R10) -CH ₂ -NH ₂ , alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl ", possibly members of this group contain up to 3 substituents independently selected from the following group:" halogen, -F, - Cl, -Br , -I, -N ₃ , -CN, -NR7R8, -OH, -NO ₂ , alkyl, aryl, arylalkyl,

-O-alkyl, -O-aryl, -O-arylalkyl "; and preferably, if R5 is selected from the group consisting of a hydrogen atom, -CO-alkyl, -CO-cycloalkyl, -CO-aryl, -CO-heteroaryl,

-CO-arylalkyl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-C * (R9R10) -NH ₂ , -CO-CH ₂ -C * (R9R10) -NH ₂ , -CO-C * (R9R10) —CH ₂ —NH ₂ , optionally containing up to 3 substituents independently selected from the following group: “halogen, —F, —Cl, —Br, —I,

"-N ₃ , -CN, -NR7R8, -OH, -NO ₂ , alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl";

R6 is selected from the group consisting of “hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl”, and preferably a hydrogen atom;

R7 and R8 are independently selected from the group consisting of "a hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl" and, preferably, a hydrogen atom;

R9 and R10 are independently selected from the group consisting of "hydrogen atom, alkyl, side chain of natural alpha amino acids, side chain of unnatural alpha amino acids", and preferably selected from the group comprising "hydrogen atom, alkyl";

m corresponds to 0, 1 or 2, preferably 0; and

* means a carbon atom in the R or S configuration, if it is chiral; which can be used in the manufacture of a medicament for the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors.

In accordance with a preferred aspect, the invention relates to compounds of the above formula (I), where

R3 is selected from the group consisting of "-alkyl-CO-aryl, -alkyl-CO-arylalkyl, - alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, alkyl-CO-heterocyclylalkyl, -alkyl -C (O) O-aryl, -alkyl-C (O) O-arylalkyl, -alkyl-C (O) O-heteroaryl, -alkyl-C (O) O-heteroarylalkyl, -alkyl-C (O) O -heterocyclyl, -alkyl-C (O) O-heterocyclylalkyl, -alkyl-CO-NH ₂ , -alkyl-CO-OH, -alkyl-NH-C (NH) -NH ₂ , alkyl-S-alkyl, alkyl- SH ", and is preferably selected from the group consisting of" -alkyl-CO-arylalkyl, -alkyl-C (O) O-arylalkyl, -alkyl-CO-NH ₂ , -alkyl-CO-OH ";

which can be used in the manufacture of a medicament for the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors.

In accordance with another preferred aspect, the invention relates to compounds according to the above formula (I), where

R4 represents a hydrogen atom;

R5 is selected from the group consisting of "hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, aryloalkylsulfonyl, -CO-cycloalkyl, , -CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-heterocyclylalkyl ";

moreover, if R5 is “—CO-heteroarylalkyl”, then “heteroaryl” is not imidazole;

and if R5 is “—CO-heterocyclyl” and “heterocyclyl” contains only nitrogen atoms as hetero atoms, then at least two nitrogen atoms are included in “heterocyclyl”;

and, if R5 is “-CO-heterocyclylalkyl” and “heterocyclyl” contains only nitrogen atoms as hetero atoms, with one or two nitrogen atoms entering the heterocyclyl, then the nitrogen atoms are not in position 1 of the heterocyclyl through which the heterocyclyl directly binds with the carbonyl group “—CO—”;

where "alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, -CO-cycloalkyl, -CO-cycloalkyl-alkyl-alkyl , -CO-heteroarylalkyl, -CO-heterocyclyl, and / or -CO-heterocyclylalkyl "may contain up to 3 substituents independently selected from the following group:" halogen, -F, -Cl, -Br, -I, -N ₃ , "-CN, -NR7R8, -OH, -NO ₂ , alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl";

moreover, if R5 represents

"-CO-cycloalkyl" or "-CO-cycloalkylalkyl", then R5 is not substituted with NR7R8 at position 1 of the "cycloalkyl", that is, at the C atom directly linking the "cycloalkyl" to the carbonyl group "-CO-" if R5 = " -CO-cycloalkyl ", or with the group" alkyl ", if R5 =" - CO-cycloalkylalkyl "; and if R5 is —CO — aryl or —CO — arylalkyl, and “aryl” is phenyl / benzene and contains only one substituent, then this substituent cannot be —NR7R8;

R6 represents a hydrogen atom;

R7 and R8 are independently selected from the group "hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl" and, preferably, represent a hydrogen atom and

m is 0, 1 or 2, more preferably 0;

which can be used in the manufacture of a medicament for the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors.

In accordance with another aspect, the object of the invention was surprisingly completed to provide compounds corresponding to formula (I), wherein

R1 is selected from the group consisting of "hydrogen, methyl, (2-methoxyphenyl) methyl, (3-methoxyphenyl) methyl, (4-methoxyphenyl) methyl, (3-methoxyphenyl) ethyl, (4-methoxyphenyl) ethyl , phenyl, phenylmethyl, phenylethyl, (4-ethylphenyl) methyl, (4-methylphenyl) methyl, (4-fluorophenyl) methyl, (4-bromophenyl) methyl, (2,4-dimethoxyphenyl) -methyl, (3,5-dimethoxyphenyl) methyl, 2,2-diphenyl-ethyl, naphthalen-1-yl-methyl, 1H-indol-3-yl-methyl, 2- (1H-indol-3-yl) Ethyl, 3- (1H-indol-3-yl) propyl, 4-methyl-phenyl, 4-ethyl-phenyl, n-hexyl, (3,4-dichlorophenyl) methyl, (4-nitro-phenyl) -methyl, (pyridin-2-yl) -methyl, (pyridin-3-yl) -methyl, (pyridin-4-yl) - etil (thiophen-2-yl) -methyl, (thiophene-3-yl) -methyl, (furan-2-yl) -methyl, (furan-3-yl) methyl ";

R2 is selected from the group consisting of “methyl, 1H-indol-3-yl-methyl, 2- (1H-indol-3-yl) -ethyl, 3- (1H-indol-3-yl) propyl, 2-phenyl ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 2-methoxy-phenylmethyl, 3-methoxy-phenylmethyl, 4-methoxy-phenylmethyl, 2-methoxy-phenylethyl, 3-methoxy-phenylethyl, 4-methoxy-phenylethyl ";

R3 is selected from the group consisting of "hydrogen atom, methyl, propan-2-yl, 2-methyl-propan-1-yl, butan-2-yl, butan-1-yl, -CH ₂ -SH, - (CH ₂ ) ₂ -S-CH ₃ , 1H-indol-3-yl-methyl, phenyl-methyl, 2-phenyl-ethyl, -CH ₂ -O-CH ₂ -phenyl, -CH ₂ -CO-CH ₂ -phenyl, - (CH ₂ ) ₂ -CO-CH ₂ -phenyl, -CH ₂ -C (O) O-phenyl, - (CH ₂ ) ₂ -C (O) O-phenyl, hydroxymethyl, 1-hydroxy-ethane -1-yl, -CH ₂ -CO-NH ₂ , - (CH ₂ ) ₂ -CO-NH ₂ , (1-hydroxy-benzene-4-yl) methyl, -CH ₂ -CO-OH,

- (CH ₂ ) ₂ —CO — OH, - (CH ₂ ) ₄ —NH ₂ , (1H-imidazol-5-yl) methyl, - (CH ₂ ) ₃ —NH-C (NH) -NH ₂ ,

- (CH ₂ ) ₃ —NH ₂ , - (CH ₂ ) ₃ —NH — CO — NH _2, ”and is preferably selected from the group consisting of“ 1H-indol-3-yl-methyl, —CH ₂ —CO— CH ₂ phenyl, - (CH ₂ ) ₂ —CO — CH ₂ phenyl,

"CH ₂ -C (O) O-phenyl, - (CH ₂ ) ₂ -C (O) O-phenyl";

R4 represents a hydrogen atom;

R5 is selected from the group consisting of "hydrogen atom, -CO-CH ₂ -NH ₂ (residue Gly), -CO-CH ₂ -CH ₂ -NH ₂ (residue beta-Ala), -CO-CHCH ₃ -NH ₂ ( residue D- and / or L-alpha-Ala),

-CO- (pyrrolidin-2-yl) (residue D- and / or L-Pro), 2-amino-2-carbonyl-propane (residue 2-amino-isobutyric acid / Aib), 4-carbonyl-1H-piperidine , 3-carbonyl-1H-piperidine, R- (3-carbonyl-1H-piperidine), S- (3-carbonyl-1H-piperidine), 2-carbonyl-1H-piperidine, R- (2-carbonyl-1H- piperidine), S- (2-carbonyl-1H-piperidine), 1-amino-2-carbonyl-benzene, carbonyl-cyclohexane, 2-acetyl-pyridine, 3-acetyl-pyridine, 4-acetyl-pyridine, 2-propionyl -pyridine, 3-propionyl-pyridine, 4-propionyl-pyridine, (R-1-amino) -2-carbonyl-cyclohexane, (S-1-amino) -2-carbonyl-cyclohexane, 2-carbonyl-1H-imidazole , 2-carbonyl-pyridine, 3-k rbonyl-pyridine, 4-carbonyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-pyrazine, 2-carbonyl-4-hydroxy-1H-pyrrolidine, 4-carbonyl-1H, 3H-diazacyclohexane, methyl- sulfonyl, phenylsulfonyl, 1-carbonyl-1-amino-2-phenylethane, phenylmethyl, 1-carbonyl-4-azide-benzene, 2-carbonyl-2,5-dihydro-1H-pyrrole, 2-carbonyl-piperazine, 2- carbonyl-1H-pyrrolidine, 2-aminoethane, carbonyl-benzene, 2-carbonyl-pyrazine, 3-carbonyl-pyrazine, 4-carbonyl-oxacyclohexane, 4-methyl-phenylsulfonyl, phenylmethyl-sulfonyl ";

R6 represents a hydrogen atom; and

m is 0;

which can be used in the manufacture of a medicament for the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors.

In accordance with a preferred aspect, the invention relates to compounds corresponding to the above formula (I), wherein R3 is selected from the group consisting of —CH ₂ —CO — CH ₂ phenyl, - (CH ₂ ) ₂ —CO — CH ₂ phenyl , -CH ₂ CO-NH ₂ ,

- (CH ₂ ) ₂ -CO-NH ₂ , -CH ₂ -CO-OH, - (CH ₂ ) ₂ -CO-OH, - (CH ₂ ) ₃ -NH-C (NH) -NH ₂ , -CH ₂ -SH, - (CH ₂ ) ₂ -S-CH ₃ ";

which can be used in the manufacture of a medicament for the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors.

In accordance with another preferred aspect, the invention relates to compounds corresponding to the above formula (I), where R5 is selected from the group consisting of "hydrogen atom, methylsulfonyl, phenylsulfonyl, carbonyl-cyclohexane,

(R-1-amino) -2-carbonyl-cyclohexane, (S-1-amino) -2-carbonyl-cyclohexane, 2-carbonyl-pyridine, 3-carbonyl-pyridine, 4-carbonyl-pyridine, 2-acetyl- pyridine, 3-acetyl-pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine, 3-propionyl-pyridine, 4-propionyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-1H-imidazole, 2-carbonyl-pyrazine, 4-carbonyl-1H, 3H-diazacyclohexane ";

which can be used in the manufacture of a medicament for the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors.

In accordance with another aspect, the object of the invention was surprisingly completed to provide novel triazole compounds selected from the group consisting of compounds 1-190 at the end of the description.

In accordance with a preferred aspect, these compounds can be used for the manufacture of a medicament for the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors.

In accordance with another preferred aspect, all triazole compounds illustrated herein generally (in accordance with the above formula (I) and various R radicals) and explicitly referred to hereinafter as the compounds of the (present) invention, can be used to produce a medicament for the treatment or prevention of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors, moreover, such treatment is carried out by modulating SSHR receptors.

In accordance with another preferred aspect, all compounds of the present invention are antagonists of SSHR receptors.

More preferably, antagonists of SSHR receptors are compounds selected from the group consisting of: Compound 1,3, 12, 13, 14, 18, 20, 22, 23, 33, 36, 37, 38, 41, 46, 47, 48 , 49, 50, 51, 52, 53, 57, 58, 59, 60, 61, 63, 64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 79 , 80, 82, 85, 86, 87, 88, 89, 90, 91, 93, 101, 102, 109, 114, 116, 119, 134, 135, 136, 137, 138, 139, 140, 145, 146 , 147, 148, 150, 152, 153, 154, 156, 157, 159, 160, 161, 164, 171, 174, 176, 178, 179, 182, 184, 186, 188 and / or Compound 190.

In accordance with another preferred aspect, all compounds of the present invention are SSHG receptor agonists. More preferably, SSHG receptor agonists are compounds selected from the group consisting of: Compound 2, 4, 5, 6, 7, 8, 9, 10, 11, 15, 16, 17, 19, 21, 24, 25, 26 , 27, 28, 29, 30, 31, 32, 34, 39, 40, 42, 43, 44, 45, 54, 55, 56, 62, 67, 78, 81, 83, 84, 87, 92, 94 , 99, 103, 104, 105, 106, 107, 108, 110, 111, 115, 117, 118, 121, 122, 124, 130, 131, 142, 155, 158, 163, 173, 175, 180, 181 , 183, 185 and / or Compound 187.

Terms used to explain the above compounds of formula (I) always, unless otherwise indicated in the description or in the claims, indicate the following.

The term “substituted” means that the corresponding radical or group contains one or more substituents. If the radical contains several substituents and it is indicated that it is possible to choose from several different substituents, then the substituents are selected independently from each other, and they are not required to be identical. The term “unsubstituted” means that the corresponding group has no substituents. The term “optionally substituted” means that the corresponding group is either unsubstituted or substituted with one or more substituents. The term “substituted with up to 3 substituents (contains up to 3 substituents)” means that the corresponding radical or group is either unsubstituted or substituted with one, two or three substituents.

The term “alkyl” for the purposes of the present invention includes acyclic saturated hydrocarbons containing C ₁ -C ₁₂ carbon atoms, which may be straight or branched.

Preferably, the term “alkyl” means alkyl chains of 1 to 8 length, particularly preferably 1 to 6 carbon atoms. Examples of suitable alkyl radicals are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, tert-pentyl, 2- or 3-methyl-pentyl, n-hexyl, isohexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl.

The term “cycloalkyl” means a saturated or partially unsaturated non-aromatic cyclic hydrocarbon radical / group containing from 1 to 3 cycles, including monocyclic alkyl, bicyclic alkyl and tricyclic alkyl, and also containing from 3 to 20 carbon atoms forming cycles, preferably from 3 up to 10, most preferably if it is (C ₃ -C ₈ ) -cycloalkyl. Examples of suitable cycloalkyl radicals are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclohexenyl, cyclopentenyl, cyclooctadienyl.

The term “cycloalkylalkyl” means a radical in which a cycloalkyl group is linked via an alkyl group, wherein the alkyl and cycloalkyl groups are as defined above, preferably a (C ₃ -C ₈ ) -cycloalkyl- (C ₁ -C ₄ ) -alkyl radical. Examples are cyclopropylmethyl, cyclohexyl methyl, cyclopentylethyl, cyclohexenylethyl.

The term "alkenyl" for the purposes of the present invention includes acyclic unsaturated or partially unsaturated hydrocarbons containing C ₂ -C ₁₂ carbon atoms, it may be straight or branched and contain one or more double bonds. Preferably, the term “alkenyl” means alkenyl chains of 2 to 8, particularly preferably 2 to 6 carbon atoms. Examples of alkenyls are vinyl, propenyl, butenyl, pentenyl, hexenyl, octadienyl and the like.

The term "alkynyl" means acyclic unsaturated or partially unsaturated hydrocarbons containing C ₂ -C ₁₂ carbon atoms, it may be straight or branched and contain one or more triple bonds. Preferably, the term "alkynyl" means alkynyl chains of 2 to 8, particularly preferably 2 to 6 carbon atoms. Examples are propynyl, butynyl, pentenyl, hexenyl.

The term “aryl” means aromatic hydrocarbon systems containing from 3 to 14, preferably from 5 to 14, carbon atoms, which can be further conjugated to form saturated, (partially) unsaturated or aromatic ring systems. Examples of aryls include, but are not limited to, phenyl, biphenyl, naphthyl, and anthracenyl, but also indanyl, indenyl, or 1,2,3,4-tetrahydronaphthyl.

The term “heteroaryl” means a 5, 6 or 7 membered cyclic aromatic radical containing at least 1 heteroatom, but may also contain 2, 3, 4 or 5 heteroatoms, preferably nitrogen, oxygen and / or sulfur, where the heteroatoms may be identical or different. Preferably, the number of nitrogen atoms ranges from 0 to 3, and oxygen and sulfur atoms from 0 to 1. The term “heteroaryl” also includes systems in which the aromatic ring is part of a bi- or polycyclic system, for example, the aromatic ring can be conjugated to an aryl, cycloalkyl, heteroaryl or heterocyclyl group as defined herein through any desired and possible atom of the heteroaryl radical ring. Examples of heteroaryl include pyrrolyl, thienyl, furyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, quinolinyl and isoquinolinyl.

The terms “arylalkyl” and “heteroarylalkyl” mean radicals in which an aryl or heteroaryl radical is linked via an alkyl group, wherein alkyl, aryl and heteroaryl are described above. Preferred “arylalkyls” are phenyl- (C ₁ -C ₄ ) -alkyl radicals, preferably benzyl or phenylethyl. Preferred “heteroarylalkyls” are indolyl- (C ₁ -C ₄ ) -alkyl radicals, preferably 1H-indol-3-yl-methyl or 2 (1H-indol-3-yl) -ethyl.

The term “heterocyclyl” means a mono- or polycyclic system containing from 3 to 14, preferably from 5 or 6 to 14 atoms in the ring, which may be exclusively carbon atoms. However, the cyclic system may also contain 1, 2, 3, 4 or 5 heteroatoms, in particular nitrogen, oxygen and / or sulfur. The cyclic system may be saturated, mono- or polyunsaturated, but may not be aromatic. If the cyclic system consists of at least two cycles, the latter can be conjugated, spiro-connected or otherwise connected in some other way. A heterocyclyl radical may be attached at any carbon or heteroatom if this leads to the formation of a stable structure. Examples include pyrrolidinyl, thiapyrrolidinyl, piperidinyl, piperazinyl, oxapiperazinyl, oxapiperidinyl and oxadiazolyl.

The term “heterocyclylalkyl” means radicals in which a heterocyclyl group is linked through an alkyl group, wherein alkyl and heterocyclyl are defined above.

The terms “alkylsulfonyl”, “arylsulfonyl” and “arylalkylsulfonyl” mean radicals in which the alkyl, aryl or arylalkyl groups are linked through an —SO ₂ group, wherein the alkyl, aryl or arylalkyl groups are as defined above. Examples are methylsulfonyl and phenylsulfonyl.

The term “halogen”, “halogen atom” or “halogen substituent” (Hal-) means one or, where possible, several atoms of fluorine (F, fluoro), bromine (Br, bromo), chlorine (Cl, chloro) or iodo (I, iodo). The phrase “dihalogen”, “trihalogen” and “perhalogen” means respectively two, three or four substituents, each of which may be independently selected from the group consisting of fluoro, chloro, bromo and iodo. Preferably, the term “halogen” means fluorine, chlorine or bromine atoms.

The term "side chain of natural alpha amino acids" means in the present invention all side chains of the known 20 proteinogenic alpha amino acids, as well as side chains of naturally occurring (that is, in any biological systems) alpha amino acids, such as, for example, selenocysteine, pyrrolysin , citrulline, ornithine, homocysteine, N-methylarginine, N-acetylysine, gamma-carboxyglutamate, 5-hydroxylisine, 3-methylhistidine and / or N, N, N-trimethyllysine. In this regard, the side chain means a residue attached to an alpha-carbon atom, for example methyl in the case of the Ala side chain or benzyl in the case of the Phe side chain.

The term "side chain of unnatural alpha amino acids" means in the present invention all side chains of known alpha amino acids that are not proteinogenic, and which are not known to occur in nature (that is, in any biological systems).

Examples are norleucine, cyclohexylglycine, 2-naphthylamine, substituted alpha-amino acids (e.g. halogen-substituted Tyr or Phe), as well as protected alpha-amino acid side chains having a protecting group such as Fmoc, Boc, Z, CBZ, Aloe , trityl, acetyl and / or benzyl is directly linked / reacted with functionalization (for example, with an amino, hydroxy and / or carboxy residue). In this regard, the term "side chain" means the same as for the "side chain of natural alpha amino acids."

The above-described R1-R10 radicals having functionalization (e.g. amino, hydroxy and / or carboxy radicals), such as alkyl-CO-NH ₂ , -alkyl-CO-OH, -alkyl-NH ₂ , -alkyl-NH-radicals C (NH) -NH ₂ , -CO-C * (R9R10) -NH ₂ , -CO-CH ₂ -C * (R9R10) -NH ₂ , -CO-C * (R9R10) -CH ₂ -NH ₂ and / or 2-amino-2-carbonyl-propane (2-amino-isobutyric acid / Aib), can be protected by the above protecting groups. Such radicals with protective groups are considered to belong to the scope and spirit of the present invention.

All stereoisomers of the compounds of the invention are included in the scope of the present invention, as a mixture or in pure or substantially pure form. The asymmetric centers of the compounds of the present invention can be located on any carbon atom, including any of the R radicals. Accordingly, the compounds of the invention can exist as racemates, pure enantiomers and / or diastereomers, or in the form of mixtures of these enantiomers and / or diastereomers. The mixture may contain any ratio of these stereoisomers. All of these various stereochemical forms and mixtures are within the scope of the present invention. For example, compounds of the invention having one or more centers of chirality and existing as mixtures of racemates or diastereomers can be resolved by known methods into optically pure isomers, i.e. enantiomers or diastereomers. The separation of the compounds of the invention can be carried out on a column with a chiral or non-chiral phase, either by recrystallization from an optically active solvent or by using an optically active acid or base, as well as by derivatization using an optically active reagent such as, for example, optically active alcohol, followed by elimination radical.

If possible, the compounds of the present invention may be in the form of tautomers.

The compounds of the invention may also exist in the form of any desired prodrug, such as, for example, esters, carbonates or phosphates; in this case, the actual biologically active substance is released only during the metabolism. Any compound that can be converted in vivo to provide a biologically active agent compound of the invention is a prodrug related to the scope and spirit of the present invention.

Various forms of prodrugs are well known in the literature and are described, for example, in the following works:

(i) The Practice of Medicinal Chemistry (Wermuth CG et al., Chapter 31, Academic Press 1996);

(ii) Design of Prodrugs (editor: Bundgaard H1 Elsevier 1985); and

(iii) A Textbook of Drug Design and Development (Krogsgaard-Larson P and Bundgaard H, eds., Chapter 5: 113-191, Harwood Academic Publishers 1991). These works are included here by reference.

It is also known that chemical compounds in the body turn into their metabolites, which can also demonstrate a biological effect - in some cases even in a more pronounced form. Any biologically active compound formed by in vivo metabolism from any compound of the present invention.

If the compounds of the present invention possess sufficiently basic groups, for example, primary, secondary or tertiary amines, they can be converted into salts by the action of inorganic and organic acids. The pharmaceutically acceptable salts of the compounds of the present invention are preferably prepared by the action of hydrochloric, hydrobromic, iodine, sulfuric, phosphoric, methanesulfonic, p-toluenesulfonic, carbonic, formic, acetic, sulfofluoroacetic, trifluoroacetic, oxalic, malonic, maleic, maleic, malic, maleic acids tartaric acids, as well as malic, embonic, manedic, fumaric, lactic, citric, tavric, glutaric, stearic, glutamic or aspartic acids. The resulting salts are, among other things, hydrochlorides, chlorides, hydrobromides, bromides, iodides, sulfates, phosphates, methanesulfonates, tosylates, carbonates, bicarbonates, formats, acetates, sulfoacetates, triflates, oxalates, malonates, maleates, succinates, tartrates malates, embonates, mandelates, fumarates, lactates, citrates, glutarates, stearates, aspartates and glutamates. Salts stoichiometrically formed from the compounds of the present invention may contain an integer and non-integer number of functional groups and residues.

If the compounds of the present invention possess sufficiently acidic groups, for example, carboxy, sulfonic, phosphoric or phenolic groups, they can be converted into physiologically tolerable salts by the action of inorganic and organic bases. Examples of suitable inorganic bases are ammonia, sodium, potassium and calcium hydroxide, and examples of organic bases are ethanolamine, diethanolamine, triethanolamine, ethylenediamine, tert-butylamine, tert-octylamine, dehydroabiethylamine, cyclohexylamine, dibenzylethylenediamine and lysine. Salts stoichiometrically formed from the compounds of the present invention may contain an integer and non-integer number of functional groups and residues.

The compounds of the present invention may also be present in the form of solvates and, in particular, hydrates, which can be obtained, for example, by crystallization from a solvent or from an aqueous solution. Moreover, one, two, three or any number of solvent or water molecules can be combined with the compounds of the present invention to obtain solvates and hydrates.

Chemicals are known to form solid precipitates that can exist in various ordering states called polymorphic forms or modifications. Various modifications of a polymorphic substance can vary greatly in their physical properties. The compounds of the present invention can exist in various polymorphic forms, and some modifications may be metastable. All of these polymorphic species of the compounds of the present invention also belong to the present invention.

The triazole derivatives (compounds of the invention) illustrated here are ghrelin-like ligands of SSHR receptors. Thus, the above compounds of the invention are suitable for the treatment or prevention of physiological and / or pathophysiological conditions mediated by SSHR receptors, as well as physiological and / or pathophysiological conditions that can be influenced by modulating these receptors, thereby preventing the development of the disease, curing it and / or facilitating its course.

As used herein, the term “treatment” also includes prophylactic treatment or alleviation of the condition.

The term "ghrelin-like ligand" or "ligand" in this application refers to any compound that somehow binds to a receptor (the receptors in this application are SSHR receptors) and inducing either activation or inhibition, and / or other possible effect to this receptor. Thus, the term “ghrelin-like ligand” or “ligand” includes agonists, antagonists, partial agonists / antagonists, inverse agonists and other ligands, which, when acting on a receptor, have a similar effect to agonists, antagonists, partial agonists / antagonists or inverse agonists .

In the present invention, the term “SSHR receptor antagonist” means compounds of the invention that bind to SSHR receptors but do not cause them to be activated correctly, as can be verified by detecting an increase in the intracellular calcium content characterizing activation of G-protein-bound receptors.

To test the ability of compounds to properly activate the receptors the degree of activation (increase of intracellular calcium) GHS- R 1a receptor test compound (at concentrations of 10 ^-6 M) compared to the degree of activation (increase of intracellular calcium content) receptor GHS- R 1a ghrelin in a concentration of 10 ^{- 6} M (100%) and with a basal level (0%). Such an analysis is quite capable of a qualified specialist. As a result of the study, the percentage of activation for each test compound is obtained. If the compound of the invention does not activate (increases the content of intracellular calcium) GHS-R 1a by at least 20% in accordance with the above specification, then it is considered that it does not cause proper activation and therefore is an antagonist of SSHR receptors. Preferably, such a compound exhibits an antagonistic effect (counteraction / reduction) with respect to an increase in the content of intracellular calcium under the action of ghrelin or other SSHRs, prevents such stimulation or acts as an inverse agonist (the inverse agonist is a ligand that binds to the same receptor binding site, as an agonist or antagonist, but causing inhibition of the basal / constitutive activity of the receptor, that is, in principle, it is an agonist with a negative property oh activity). Similar compounds may also exhibit inhibitory activity on GH secretion and / or other physiological or pathophysiological conditions or effects, such as food intake or lipogenesis. Their effects may be dissociated. So, such compounds can completely influence the secretion of GH, but inhibit other physiological effects. They can even stimulate other physiological effects.

In the present invention, the term “SSHR receptor agonist” means compounds of the invention that bind to SSHR receptors and cause their proper activation, as can be verified by detecting an increase in intracellular calcium content characterizing the activation of G-protein bound receptors.

If the compound of the invention activates (increases the content of intracellular calcium) GHS-R 1a by at least 20% in accordance with the above specification, then it is considered that it causes proper activation, and therefore is an agonist of the SSHR receptors. Such compounds can mimic the effect of ghrelin and / or SSHR on GH secretion and, for example, on food intake or lipogenesis. As with antagonists, the effects of agonists can be dissociated from GH secretion. So, such compounds can even antagonize (counteract / reduce) an increase in the content of intracellular calcium under the action of ghrelin or other SSHR.

The term "SSHR receptor" or "GHS-R" in accordance with the present invention means receptors that bind to at least one known peptidyl and / or non-peptidyl SSHR and / or ghrelin. The term "SSHR receptor" or "GHS-R" also means various SSHG binding sites in various tissues and / or organs, as illustrated herein, that bind to at least one known peptidyl and / or non-peptidyl SSHR and / or ghrelin and which are still uncharacterized subtypes of GHS-R.

An experienced specialist, using his experience and knowledge, can easily verify the fact of binding of the known peptidyl and / or non-peptidyl SSHR and / or ghrelin, for example, using an appropriate binding analysis representing the routine of the experimenter. Such SSHR receptors can be stimulated / activated by ghrelin (ghrelin-responsive), but may not be stimulated / activated by ghrelin (ghrelin-non-responsive) - and this applies to both acylated and non-acylated ghrelin, respectively. Stimulation / activation of such receptors may, but does not necessarily, cause GH production and / or GH secretion and / or increased GH in plasma.

Preferably, such CCG receptors are selected from the group consisting of type 1 GHS receptor, GHS-R 1a, GHS-R 1 b, motilin receptor, motilin receptor 1a, neurotensin receptor, TRH receptor, TRH receptor, GPR38 (FM1 ), GPR39 (FM2), FM3, GHS-binding site, subtype GHS-R, GHS-R of the heart muscle and mammary gland.

More preferably, such SSHR receptors are selected from the group consisting of type 1 GHS receptor, GHS-R 1a, GHS-R 1b, and most preferably GHS-R 1a.

As already shown, SSHR receptors (including SSHG-binding sites and subtypes of GHS-R) are concentrated in the pituitary-hypothalamic region, but are also found in other central and peripheral tissues.

Moreover, they are also expressed in various tumor tissues, even in tumor tissues of organs that do not express these receptors under physiological conditions.

In accordance with the present invention, all of these organs and / or tissues expressing SSHR receptors (including SSHG-binding sites and subtypes of GHS-R) are within the scope of the present invention. An experienced specialist, using his experience and knowledge, can easily establish the expression of SSHR receptors (including SSHG-binding sites and subtypes of GHS-R), for example, using the appropriate molecular biological method of analysis, such as immunofluorescence or immunoprecipitation, representing the routine of the experimenter.

Preferably, such SSHR receptors are located in tissues and / or organs selected from the group consisting of endocrine tissues, exocrine tissues, peripheral tissues, adipose / adipose tissue, brain, hypothalamus, thalamus, hippocampus, striatum, cerebral cortex, pituitary gland, central nervous system, spinal cord, glands, adrenal glands, thyroid gland, salivary glands, mammary glands, neuron, abdominal cavity, intestines, stomach, heart, liver, pancreas, kidneys, bile, urinary and gall bladder, prostate, spleen, muscles skeleton mute muscles, aorta, veins, arteries, immune cells, white blood cells, lymphocytes, T cells, B cells, granulocytes, monocytes, macrophages, dendritic cells, mast cells, NK cells, neutrophils, eosinophils, basophils, lymph node, bone, bone brain, amygdala, thymus, placenta, testes, ovaries, uterus, lung, adipocytes, tumor / cancer cells, carcinoma cells, prostate cancer cells, thyroid cancer cells, lung cancer cells, breast cancer cells.

As already shown, the compounds of the present invention are ghrelin-like ligands of SSHR receptors. They can be administered to various types of mammals, including humans, for the treatment or prevention of physiological and / or pathophysiological conditions in such mammals.

The scope of the invention includes all mammals. Preferably, such mammals are selected from the group consisting of humans, domestic animals, calves, cattle, small domestic animals, a cow, a sheep, a pig, a goat, a horse, a pony, a monkey, a monkey, a mule, a hare, a rabbit, a cat, a dog, guinea pig, hamster, rat, mouse. The most preferred animal is human.

The compounds of the present invention are non-peptide ghrelin-like ligands of SSHR receptors and are characterized, surprisingly, by a strong binding affinity for such receptors. For example, upon binding to GHS-R 1a, such compounds may preferably exhibit an IC _{50 of} less than 1000 nM. More preferably, if they exhibit an IC _{50 of} less than 500 nM, even more preferably if less than 300 nM, and most preferably if less than 100 nM.

Due to the surprisingly strong binding to receptors, the compounds of the invention can advantageously be administered at lower doses compared to other less strongly binding substances, while achieving the same or even more pronounced biological effect. In addition, such a dose reduction may favorably lead to less medical side effects or even to their absence. Moreover, the high binding specificity of the compounds of the invention can lead to a reduction in undesirable side effects in and of itself, regardless of the dose used.

Moreover, due to its non-peptide nature, the compounds of the invention are resistant to degradation by enzymes of the gastrointestinal tract. Thus, one of the advantages of their use is the possibility of administration via the oral route. They exhibit surprisingly high metabolic stability and / or improved bioavailability. Repeating again, the compounds of the present invention can advantageously reduce the dosage, which leads to fewer side effects or their absence.

As shown and defined herein, the compounds of the invention may be antagonists or agonists of SSHR receptors. Antagonists of the SSHR receptors of the present invention can, for example, be used to inhibit SSHR receptors stimulated by ghrelin and / or other SSHRs, thereby reducing or blocking the production and / or secretion of GH and / or plasma GH. In addition, such SSHR receptor antagonists can be used to inhibit or prevent the physiological or pathophysiological effects of ghrelin unrelated to GH production or secretion.

Thus, antagonists of SSHR receptors of the present invention are suitable for the treatment and / or prophylaxis of the various physiological and pathophysiological conditions described herein, in particular for short-term, medium-term and long-term regulation of energy balance, short-term, medium-term and long-term regulation (stimulation and / or inhibition) food intake, treatment of adipogenesis, obesity and / or obesity, weight gain and / or to reduce and treat tumor cell proliferation.

On the contrary, agonists of the SSHR receptors of the present invention can, for example, be used to activate SSHR receptors and stimulate / enhance the production and / or secretion of GH, and thus they have the same effects and find the same uses as the growth hormone itself, ghrelin and / or known SSGR.

Thus, the SSHR receptor agonists of the present invention are suitable for the treatment and / or prophylaxis of various physiological and pathophysiological conditions described here, in particular, growth retardation, cachexia, inflammatory processes and effects, gastric postoperative obstruction, postoperative obstruction and / or gastrectomy (ghrelin replacement therapy) .

All physiological and / or pathophysiological conditions mediated by SSHR receptors are within the scope of the present invention. Preferably, if these physiological and / or pathophysiological conditions are selected from the group consisting of the following conditions: acute fatigue syndrome and loss of muscle mass after selective surgery, adipogenesis, obesity, age-related weakening of the function of the thymus, age-related functional deviation in the elderly, age-related abnormalities in domestic animals, Alzheimer's disease, anorexia (for example, associated with cachexia or aging); anxiety, low blood pressure, decrease / increase in body weight, restoration of bones after fractures (acceleration of the process), stimulation of bone remodeling, cachexia and loss of proteins due to chronic diseases such as cancer or AIDS, cardiovascular dysfunctions (e.g. associated with valve disease, myocardial infarction, cardiac muscle hypertrophy or congestive heart failure), cardiomyopathy, stimulation of cartilage growth, catabolic disorders associated with pulmonary dysfunction and dependence on the mechanical ventilation system, catabolic side effects of glucocorticoid use, catabolic state of aging, central nervous system disorders (together with antidepressants), chronic dialysis, chronic fatigue syndrome, improved cognitive function (for example, with dementia or Alzheimer's disease), complicated fractures (e.g., osteogenesis disorders) associated with transplantation complications, congestive heart failure (can be treated in conjunction with an antagonist and corticotropin-releasing factor), Crohn's disease and ulcerative colitis, Cushing's syndrome, dementia, depression, short-term and / or long-term regulation of energy balance, short-term, medium-term and / or long-term regulation of food intake (stimulation and / or inhibition), bone fragility ( for example, in the elderly), gastrectomy (ghrelin replacement therapy), gastric postoperative obstruction, improved glycemic control, stimulation of the release of growth hormone in the elderly, replacement of growth hormone in the strain patients, growth stimulation in livestock, growth retardation associated with Prader-Willi syndrome and Turner syndrome, growth retardation due to Crohn's disease, growth retardation, hair / nail growth support, hip fractures, hunger, hypercortisolism, hyperinsulinemia, including nezidioblastosis, hypothermia, immune deficiency in people with a low T4 / T8 cell ratio, improved immune response during vaccination, stimulation of the immune system in domestic animals, stimulation of the immune system patterns, immune suppression in patients with such suppression, inflammation or inflammatory effects, intestinal inflammation, insulin resistance in the heart, insulin resistance in patients with type 2 diabetes, insulin resistance, including NIDDM, diabetes, type 1 diabetes, type 2 diabetes type, intrauterine growth retardation, irritable bowel syndrome, lipodystrophy (e.g., HIV induction), maintenance of metabolic homeostasis, increased cattle milk yield, increased muscle mass / strength, improving muscle mobility, increasing muscle strength, maintaining muscle strength / functioning in the elderly, muscle atrophy, musculoskeletal abnormalities (e.g. in the elderly), Noonan syndrome, obesity and its associated growth retardation, stimulation of osteoblasts, osteochondrodysplasia, osteoporosis, induction ovulation (adjunctive treatment), physiological short stature, including growth hormone deficiency in children, postoperative obstruction, weakening of the protein catabolic response after extensive surgery or injuries, increased activity of protein kinase B, psychosocial deprivation syndrome, pulmonary dysfunction and dependence on mechanical ventilation devices, improved lung function, pulsating induction of growth hormone secretion, treatment of burns and reduced hospitalization time for patients with burns (accelerated healing), renal failure caused by stunted growth, maintaining renal homeostasis and older people with increased fragility of the physique, sarcopenia, schizophrenia, maintaining sensory functions (e.g. hearing, vision, smell and taste), short bowel syndrome associated with a chronic disease, small stature, skeletal dysplasia, maintaining skin thickness, sleep disturbances, improving sleep quality, thrombocytopenia, stimulating the development of thymus, restoring or growing teeth, proliferation tumor cells, ventricular dysfunction or cases of reperfusion, AIDS-related exhaustion, chronic liver disease depletion, exhaustion due to chronic obstructive pulmonary disease ( chronic obstructive pulmonary disease (COPD)), exhaustion associated with multiple sclerosis or other neurodegenerative diseases, exhaustion associated with fractures, stimulation of hair growth in sheep, accelerated wound healing, delayed wound healing. More preferably, these physiological and / or pathophysiological conditions are selected from the group consisting of growth retardation, cachexia, short-term, medium-term, and / or long-term regulation of energy balance; short-term, medium-term and / or long-term regulation (stimulation and / or inhibition) of food intake; adipogenesis, obesity and / or obesity; increase and / or decrease in body weight; diabetes, type 1 diabetes, type 2 diabetes, tumor cell proliferation; inflammation, effects of inflammation, gastric postoperative obstruction, postoperative obstruction and / or gastrectomy (ghrelin replacement therapy).

In accordance with an additional aspect of the present invention, the compounds of the invention can be used in conjunction with at least one additional pharmacologically active substance. Such additional pharmacologically active substances may be other compounds of the present invention and / or other “suitable therapeutic agents” useful in the treatment and / or prevention of the above physiological and / or pathophysiological conditions. Additional pharmacologically active substances may be antagonists of SSHR receptors and / or agonists of SSHR receptors, depending on the purpose of the combined use. The selection and combination of additional pharmacologically active substances (substances) can easily be carried out by a qualified specialist on the basis of their expert knowledge and depending on the purpose of the joint use, as well as on the physiological and / or pathophysiological state for which the medicine will be used.

In accordance with a preferred aspect, the compounds of the invention are used for the treatment and / or prophylaxis of the aforementioned physiological and / or pathophysiological conditions in the form of a medicament, wherein the medicament contains at least one additional pharmacologically active substance.

In accordance with another preferred aspect, the compounds of the invention are used for the treatment and / or prophylaxis of the aforementioned physiological and / or pathophysiological conditions in the form of a medicament, where such a medicament is used before and / or during and / or after treatment with at least one additional pharmacologically active substance .

The “additional therapeutic agents” mentioned above include: SSHR, antidiabetic agents; anti-obesity agents; anti-inflammatory agents; anxiety treatment agents; antidepressants; anti-hypertensive agents; anti-platelet agents; antithrombotic and thrombolytic agents; cardiac glycosides; substances to lower cholesterol / lipids; mineralocorticoid receptor antagonists; phosphodiesterase inhibitors; protein tyrosine kinase inhibitors; thyroid mimetics (including thyroid receptor antagonists); anabolic agents; HIV or AIDS treatments medicines useful for treating Alzheimer's disease and other cognitive disorders; medications useful for treating sleep disorders; anti-proliferative agents; antitumor agents; remedies for ulcers and gastroesophageal reflux; progestin receptor agonists ("PRA"); estrogen; testosterone; selective estrogen receptor modulators; selective androgen receptor modulators; parathyroid hormone and / or bisphosphonate. Preferably, "suitable therapeutic agents" have also been selected from the specified group.

Examples of suitable GCGR for use with the compounds of the present invention include GHRP-6, GHRP-1 described in US patent No. 4411890 and publications WO 89/07110 and WO 89/07111, as well as B-HT920 or growth hormone release factor and its analogues or growth hormone and its analogs or somatomedins, including IGF-1 and IGF-2, as well as SSGR described in WO 01/96300.

Examples of suitable antidiabetic agents for use with the compounds of the present invention include biguanides (e.g. metformin), glucosidase inhibitors (e.g. acarbose), insulins (including insulin secretagogues or insulin sensitizers), meglitinides (e.g. repaglinide), sulfonylureas, e.g. glibutiride and glipizide), biguanide / glyburide combinations (e.g. glucovans), thiosolidinediones (e.g. troglitazone, rosiglitazone and pioglitazone) PPAR alpha agonists, PPAR gamma agonists; double PPAR alpha / gamma agonists, SGLT2 inhibitors, fatty acid binding protein (aP2) inhibitors, such as those described in US patent 6548529, glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase IV inhibitors (DP4).

Examples of suitable osteoporosis agents used in conjunction with the compounds of the present invention include alendronate, risedronate, raloxifene, calcitonin, non-steroidal protestin receptor agonists, RANK ligand agonists, calcium recognition receptor antagonists, TRAP inhibitors, selective estrogen receptor modulators and AR-inhibitors, est one.

Examples of suitable obesity treatment agents used in conjunction with the compounds of the present invention include endocannabinoid receptor antagonists, e.g. CB1 receptor antagonists such as rimonabant (1H-pyrazole-3-carboxamide, 5- (4-chlorophenyl) -1- (2, 4-dichlorophenyl) -4-methyl-H-1-piperidinyl-, monohydrochloride; US Pat. No. 5,624,941), aP2 inhibitors such as described in US Pat. No. 6,548,529, PPAR-gamma antagonists, PPAR-delta agonists and orlistat.

Examples of suitable anti-inflammatory agents used in conjunction with the compounds of the present invention include prednisone, dexamethasone, Enbrel, cyclooxygenase inhibitors (i.e., COX-1 and / or COX-2 inhibitors such as NSAID, aspirin, indomethacin, ibuprofen, piroxicam, Naproxen, Celebrex , Vioks), CTLA4-lg agonists / antagonists, CD40 ligand antagonists, integrin antagonists, alpha4 beta7 integrin antagonists, cell adhesion inhibitors, gamma interferon antagonists, ICAM-1, tumor necrosis factor (TNF) antagonists (e.g., inflix mab, OR1384), prostaglandin synthesis inhibitors, budesonide, clofazimine, CNI-1493, CD4 antagonists (e.g. priliximab), p38 mitogen-activated protein kinase inhibitors, tyrosine kinase protein (PTK) inhibitors, IKK inhibitors, agents for treating the syndrome intestines (for example, zelmak and Maxi-K channel openers, such as those described in US Pat. No. 6,184,231).

Examples of suitable anxiety treatment agents used in conjunction with the compounds of the present invention include diazepam, lorazepam, buspirone, oxazepam and hydroxyzine pamoate.

Examples of suitable candidates for use with the compounds of the present invention include citalopram, fluoxetine, nefazodone, sertraline and paroxetine.

Examples of suitable antihypertensive agents used in conjunction with the compounds of the present invention include beta adrenergic blocking agents, calcium channel blockers (L-type and R-type; for example, diltiazem, verapamil, nifidipine, amlodipine and mibifradil), diuretics (for example, chlorothiazide, hydrochlorothiazide, , hydroflumethiazide, bendroflumethiazide, methylchlorothiazide, trichloromethiazide, polythiazide, benzthiazide, ethacrine tricrinaphene, chlortalidone, furozemide, musolimin, bumetanide, triamtrenene, amiloride, spironolactone), inhibi renin tori, ACE inhibitors (e.g. captopril, zofenopril, fosinopril, enalapril, ceranopril, cilazopril, delapril, pentopril, quinapril, rapipril, lisinopril), AT-1 receptor antagonists (e.g. losartan, irbesartan, for example, sitaxentan, atrsentan, and compounds from US patents 5612359 and 6043265), ET / AII double antagonists (e.g., compounds from WO 00/01389), neutral endopeptidase inhibitors (NEP), vasopeptidase inhibitors (double NEP-ACE inhibitors) ( e.g. omapatrilate and hematoprilat) and nitrates.

Examples of suitable anti-platelet agents used in conjunction with the compounds of the present invention include GPIIb / IIIa blockers (e.g., abciximab, eptifibatide, tirofiban), P2Y12 antagonists (e.g. clopidogrel, ticlopidine, CS-747), thromboxane receptor antagonists (e.g. ipetroban) aspirin and PDE-III inhibitors (e.g. dipyridamole) with or without aspirin.

Examples of suitable cardiac glycosides used in conjunction with the compounds of the present invention include digitalis and ouabain. Examples of suitable cholesterol / lipid lowering agents used in conjunction with the compounds of the present invention include HMG-CoA reductase inhibitors [eg, pravastatin, lovastatin, atorvastatin, simvastatin, NK-104 (called itavastatin or nisvastatin or nisbastatin) and ZD-4522 (called rosuvastatin, atavastatin or visastatin)], squalene synthetase inhibitors, fibrates, bile acid sequestrants, ACAT inhibitors, MTP inhibitors, lipoxygenase inhibitors, cholesterol absorption inhibitors, and p cholesterol ester transfer rotin (e.g. CP-529414).

Examples of suitable mineralocorticoid receptor antagonists used in conjunction with the compounds of the present invention include spironolactone and eplerinone.

Examples of suitable phosphodiesterase inhibitors used in conjunction with the compounds of the present invention include PDE III inhibitors such as cilostazol and PDE V inhibitors such as sildenafil. Examples of suitable thyroid mimetics used in conjunction with the compounds of the present invention include thyrotropin, polythyroid, KB-130015, and dronedarone.

Examples of suitable anabolic agents used in conjunction with the compounds of the present invention include testosterone and SARM (selective androgen receptor modulators).

Examples of suitable drugs for HIV or AIDS therapy used in conjunction with the compounds of the present invention include indinavir sulfate, saquinavir, saquinavir mesylate, amprenavir, ritonavir, lopinavir, combinations of ritonavir / lopinavir, lamivudine, zidovudine, combination of lamivudine / zidovidine, davzaltine, and megestrol acetate.

Examples of suitable agents for the treatment of Alzheimer's disease and cognitive impairment used in conjunction with the compounds of the present invention include donezepil, tacrine, revastigmine, 5HT6, gamma secretase inhibitors, beta-secretase inhibitors, SK channel blockers, Maxi-K blockers and KCNQ blockers.

Examples of suitable agents for treating sleep disorders used in conjunction with the compounds of the present invention include melatonin analogs, melatonin receptor antagonists, ML1 B agonists and GABA / NMDA receptor antagonists.

Examples of suitable antiproliferative agents used in conjunction with the compounds of the present invention include cyclosporin A, taxol, FK 506 and adriamycin.

Examples of suitable antitumor agents used in conjunction with the compounds of the present invention include taxol, adriamycin, epothilones, cisplatin or carboplatin.

Examples of suitable selective exogenous receptor modulators used in conjunction with the compounds of the present invention include tamoxifen and raloxifene.

Examples of suitable selective androgen receptor modulators used in conjunction with the compounds of the present invention include those described by Edwards, J. P. et al., Bio. Med. Chem. Let, 9, 1003-1008 (1999) and Hamann, L.G. et al., J. Med. Chem., 12, 210-212 (1999).

Examples of suitable bisphosphonates used in conjunction with the compounds of the present invention include MK-217 (alendronate). If the other therapeutic agents described above are used in conjunction with the compounds of the present invention, their number may correspond, for example, to that indicated in the Physicians' Desk Reference, or it may be determined by a person skilled in the art.

In accordance with a preferred aspect, the compounds of the present invention are used to treat and / or prevent the above physiological and / or pathophysiological conditions in the form of a medicament, which medicament contains an additional pharmacologically active substance, an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant ( 1H-pyrazole-3-carboxamide, 5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methyl-H-1-piperidinyl, monohydrochloride; US patent 5624941) and compound nenie invention as an antagonist of GHS-R.

In accordance with another preferred aspect, the compounds of the present invention are used to treat and / or prevent the aforementioned physiological and / or pathophysiological conditions in the form of a medicament, the medicament being used before, during or after treatment with at least one additional pharmacologically active substance, where such the additional pharmacologically active substance is an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably, rimonabant (1H-pyrazole-3-carboxamide, 5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methyl-H-1-piperidinyl-, monohydrochloride; US Pat. No. 5,624,941), and the compound The invention is used as an antagonist of GHS-R.

The compounds of the present invention can be administered in a known manner. The route of administration can be any route that allows the active compound to be transported efficiently to the appropriate desired site of action, for example, it can be oral or non-oral administration, in particular topical, transdermal, pulmonary, rectal, intravaginal, nasal or parenteral, and can also be administered by implantation . Oral administration is preferred. The compounds of the invention are converted into a form in which they can be administered and, if desired, mixed with pharmaceutically acceptable carriers or diluents. For example, suitable excipients and carriers are described in Ullman's Encyclopedia (Ullman's Encyclopedia of Technical Chemistry, Vol.4 (1953), 1-39); and also in Journal of Pharmaceutical Sciences, Vol. 52 (1963), 918 et seq .; H.v. Czetsch-? Ndenwald, "Hilfsstoffe fur Pharmazie and angrenzende Gebiete"; Pharm. Ind. 2, 1961, 72 et seq .; Dr. H.P. Fiedler, "Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik and angrenzende Gebiete", Cantor KG, Aulendorf in W? Rttemberg, 1971.

Oral administration may be carried out, for example, in solid form, such as tablets, capsules, gel capsules, coated tablets, granules or powders, but may also be in the form of a potable solution. The compounds of the invention for oral use can be combined with known and common physiologically tolerable excipients and carriers, such as, for example, gum arabic, talc, starch, sugars, for example, mannitol, methyl cellulose, lactose, gelatin, surface active agents, magnesium stearate, cyclodextrins , aqueous or non-aqueous vehicles, diluents, dispersants, emulsifiers, lubricants, preservatives and flavorings (e.g., aromatic oils). The compounds of the invention can also be dispersed to form a microparticulate, for example nanoparticulate, composition.

Non-oral administration can be carried out, for example, by intravenous, subcutaneous, intramuscular injection of a sterile aqueous or oily solution, suspension or emulsion, by implants, ointments, creams or suppositories. If appropriate, delayed release formulations may also be administered. The implants may contain inert substances, for example, biodegradable polymers or synthetic silicones, such as, for example, silicone rubber. Intravaginal administration can be carried out, for example, using vaginal rings. For intrauterine administration, for example, diaphragms or other suitable intrauterine devices can be used. Transdermal administration is also possible, in particular using formulations and / or devices suitable for this purpose, such as patches.

Dosages can vary over a wide range, depending on the type and / or intensity of the physiological and / or pathophysiological condition, administration regimen, age, gender, body weight, and sensitivity of the treatment subject. An experienced physician may determine the “pharmacologically effective amount” of a compound of the invention and / or an additional pharmacologically active substance. The introduction can be carried out once or several times.

A suitable dosage unit may contain, for example, from 0.001 to 100 mg of the active ingredient, that is, at least one compound of the invention and, if necessary, at least one additional pharmacologically active substance, per kilogram of patient body weight.

In accordance with another aspect, the present invention relates to a pharmaceutical composition comprising at least one triazole compound selected from the group consisting of compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 , 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38 , 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 , 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88 , 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113 , 114, 115, 116, 117, 118, 119, 120, 121, 122, 124, 125, 126, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140 , 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189 and / or compounds 190.

In accordance with a further aspect, such a pharmaceutical composition may further comprise at least one pharmaceutically acceptable carrier and / or excipient and / or may contain at least one additional pharmacologically active substance.

In a preferred aspect, such an additional pharmacologically active substance is an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant [1H-pyrazole-3-carboxamide, 5- (4-chlorophenyl) -1- (2,4- dichlorophenyl) -4-methyl-H-1-piperidinyl-, monohydrochloride].

Regarding the pharmaceutical compositions of the invention, at least one triazole compound of the above is presented in a pharmacologically effective amount, preferably in a dosage unit, for example, in the dosage mentioned above, specifically and preferably, in the form of an administration that enables the oral route. Moreover, here you can make a reference to what has already been said in connection with the possible uses and introduction of the compounds of the invention.

General synthesis schemes

The compounds of the present invention can be prepared in accordance with the following general synthesis schemes, as well as in accordance with the procedures described in the literature, known to the competent specialist (for example, WO 00/54729, including the references therein). The following and working examples provide examples of reagents and procedures for these reactions. Unless otherwise indicated, the meanings of the various substituents (radicals) of the compounds are as defined for formula (I) of this application.

The formation of an amide bond (peptide conjugation) is carried out in accordance with standard methods of peptide conjugation, known in the literature. It is optimal to carry out the reaction in a solvent such as dichloromethane (DCM) at room temperature using benzotriazol-1-yl-oxytris (dimethylamino) phosphonium hexafluorophosphate (BOP) (Castro B et al., Tetpahedron Lett. 1975, 14: 1219-1222 ) and a base such as N-methyl-morpholine or diisopropylethylamine.

The thionation of the amide formed was carried out using the Lawesson reagent (Pons JF et al., Tetpahedron Lett. 2000, 41: 4965-4968). Cyclization: the resulting thioamide was then subjected to a new transformation under the conditions described by Hitosuyanagi et al. (Hitotsuyanagi Y. et al., J. Org. Chem. 2002, 67: 3266-3271) and slightly modified (5 equiv. Hydrazide and 1.1 equiv. Mercury (II) acetate in acetonitrile). In general, cyclization to triazoles occurred within three hours. If the hydrazide was not commercially available, then it was prepared by known methods from the acid or methyl ester precursor.

The deprotection of the tert-butyloxycarbonyl group (BOC) was carried out at room temperature in an acidic environment, as such a procedure is usually described.

For R5 = -CO-alkyl, -CO-cycloalkyl, -CO-cycloalkylalkyl, -CO-aryl, -CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-heterocyclylalkyl, -CO -C * (R9R10) -NH ₂ , -CO-CH ₂ -C * (R9R10) -NH ₂ , -CO-C (R9R10) -CH ₂ -NH ₂ (R) the following reaction takes place:

For R5 = alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl (R), the following reaction is performed:

For = alkyl-SO ₂ -, aryl-SO ₂ -, arylalkyl-SO ₂ - (R = alkyl, aryl, arylalkyl), the following reaction is performed:

The names of the compounds of the present invention, especially compounds 1 to 190, were derived from the drawn formulas using Chem Draw Ultra 8 software (Cambridge Soft Corporation, Cambridge, USA).

The contents of all cited publications, including patents, are incorporated herein by reference. The present invention is explained in more detail in the following examples, which, however, do not limit its scope.

Examples

I) Synthesis of compounds of the invention

Example 1:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 1)

Compound 1 was obtained from BOC- (D) -Trp (10 nmol), (2,4-dimethoxyphenyl) methanamine, 3- (1H-indol-3-yl) propanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with the general scheme of synthesis. The total yield after purification by HPLC (high performance liquid chromatography) was 35%.

¹ N NMR (400 MHz, 300 K, DMSO-d ⁶ ):

δ (1.32 (3H, s, CH ₃ Aib), 1.36 (3H, s, CH ₃ Aib), 2.93 (2H, pl, CH ₂ -CH ₂ -indole), 2.97 (2H, m, CH ₂ - CH ₂ -indole), 3.31 (1Н, dd, J = 14.5, J = 6.1, 1Н СН ₂ βTrp), 3.38 (1Н, dd, J = 14.5, J = 9.1, 1H CH ₂ βTrp), 3.66 (3H, s, o-OCH ₃ ), 3.72 (3H, s, p-OCH ₃ ), 4.93 (1 H, d, J = 16.9, 1H CH ₂ о, para-dimethoxybenzyl), 5.10 (1H, d, J = 16.9, 1H CH ₂ о, para-dimethoxybenzyl), 5.23 (1 H, m, CαH Trp), 6.31 (1H, dd, J = 8.5, J = 1.7, H ₅ о, para-dimethoxybenzyl), 6.45 (1H, d, J = 8.5, H ₆ about, para-dimethoxybenzyl), 6.59 (1H, d, J = 1.7, H ₃ about, para-dimethoxybenzyl), 6.88 (1H, t, J = 7.5, H ₅ Trp), 6.94 (1H, 1, J = 7.5, H ₅ indole), 7.04 (1H, t, H ₆ indole), 7.06 (1H, t, H ₆ indole), 7.08 (1H, s, H ₂ indole), 7.11 (1H, s, H ₂ Trp), 7.18 (1H, d, J = 7.9, H ₄ Trp), 7.33 (3H, H ₄ , H ₇ indole, H ₇ Trp), 8.05 (2H, s, NH ₂ Aib), 8.95 (1 H, d, J = 7.9, NH Trp), 10.80 (1H, s, NH in dol), 10.82 (1H, s, NH indol Trp).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

δ 22.4 (CH ₂ - C H ₂ indole), 23.2 (CH ₃ Aib), 23.3 (CH ₃ Aib), 25.4 ( C H ₂ -CH ₂ indole), 28.7 (Cβ Trp), 41.3 ( C H ₂ - о , para-dimethoxybenzyl), 45.3 (Cα Trp), 55.2 (para-OCH ₃ ), 55.4 (o-OCH ₃ ), 56.3 (Cq Aib), 98.6 (C ₃ o, para-dimethoxybenzyl), 104.7 (C ₅ o , p-dimethoxybenzyl), 109.5 (C ₃ Trp), 111.3 (C ₇ Trp, C ₇ indole), 112.9 (C ₃ indole), 115.2 (C ₁ о, p-dimethoxybenzyl), 117.8 (C ₄ indole), 117.9 (C ₄ Trp), 118.2 (C ₅ Trp, C ₅ indole), 120.9 (C ₆ Trp, C ₆ indole), 122.4 (C ₂ indole), 124.3 (C ₂ Trp), 126.8 (C ₉ indole), 126.9 (C ₉ Trp), 127.5 (C ₆ about, para-dimethoxybenzyl), 136.0 (C ₈ Trp), 136.2 (C ₈ indole), 154.6 (2Cq triazole), 157.3 (C ₂ about, para-dimethoxybenzyl), 160.4 ( C ₄ about, para-dimethoxybenzyl), 171.3 (CO Aib).

ESI-MS: measured: m / z 606.3 [M + H] ⁺ / calculated: 604.3 g / mol

Example 2:

(R) -N- (1- (5-benzyl-4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 4)

Compound 4 was obtained from BOC- (D) -Trp (10 nmol), naphthalen-1-yl-methanamine, 2-phenylacetohydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with the general synthesis scheme. The total yield after purification by HPLC was 42%.

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.18 (3H, s, CH ₃ Aib), 1.24 (3H, s, CH ₃ Aib), 3.17 (1H, dd, J = 14 Hz and 5 Hz, CH ₂ βTrp), 3.36 (1H, dd , J = 14 and 9 Hz, CH ₂ βTrp), 4.05 (2H, m, CH ₂ -benzyl), 4.90 (1 H, m, CHα Trp), 5.65 (1 H, d, J = 18 Hz, CH ₂ naphthyl), 5.81 (1H, d, J = 18 Hz, CH ₂ - naphthyl), 6.12 (1H, d, J ₀ = 7 Hz, H ₂ naphthyl), 6.38 (1H, t, J ₀ = 7 Hz, H ₅ Trp), 6.47 (1H, d, J ₀ = 8 Hz, H ₄ Trp), 6.85 (1H, t, J ₀ = 8 Hz, H ₆ Trp), 7.03 (1H, d, J _m = 2 Hz , H ₂ Trp), 7.05-7.12 (5H, m, CHar benzyl), 7.15 (1H, d, J ₀ = 8 Hz, H ₇ Trp), 7.19 (1H, d, J ₀ = 8 Hz, H ₃ naphthyl ), 7.58 (2H, m, H ₆ and H ₇ naphthyl), 7.81 (1H, d, J ₀ = 8 Hz, H ₄ naphthyl), 7.89-8.01 (5H, m, NH ₂ Aib, H ₅ and H ₈ naphthyl), 8.92 (1H, d, J = 8 Hz, NH amide), 10.73 (1H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.5 (CH ₃ Aib), 23.6 (CH ₃ Aib), 29.2 (CH ₂ βTrp), 30.5 ( С Н _2- benzyl), 44.0 ( С Н _2- naphthyl), 45.6 (CH αTrp)), 56.6 (Cq Aib), 109.7 (C ₃ Trp), 111.7 (C ₇ Trp), 117.9 (C ₄ Trp), 118.4 (C ₅ Trp), 121.1 (C ₆ Trp), 122.1 (C ₂ naphthyl), 122.8 ( C ₈ naphthyl), 124.9 (C ₂ Trp), 125.7 (C ₃ naphthyl), 126.7 (C ₆ naphthyl), 126.9 (C ₉ Trp), 127.0 (C ₇ naphthyl), 128.2 (C ₄ benzyl), 128.7-129.1 (C ₂ , C ₃ , C ₅ and C ₆ benzyl, C ₄ and C ₅ naphthyl), 129.9 (C ₉ naphthyl), 131.5 (C ₁ naphthyl), 133.5 (C ₁₀ naphthyl), 136.2 (C ₁ benzyl), 136.4 (C ₈ Trp), 154.2 (Cq triazole), 155.7 (Cq triazole), 171.9 (CO Aib).

ESI-MS: measured: m / z 543.4 [M + H] ⁺ / calculated: 542.2 g / mol

Example 3:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide

(Compound 5)

Compound 5 was obtained from BOC- (D) -Trp (10 nmol), naphthalen-1-yl-methanamine, 3- (1H-indol-3-yl) propanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with general synthesis scheme. The total yield after purification by HPLC was 33%.

¹ N NMR (400 MHz, DMSO-d ⁶ , 300 K):

-СН₂-индол), 3.01 (2Н, m, СН₂-

-индол), 3.30 (1Н, dd, 3J=14.3 и 5.8 Hz, СН₂ βTrp), 3.40 (1Н, dd, 3J=14.3 и 8.8 Hz, CH₂ βTrp), 5.03 (1Н, m, СН αTrp), 5.62 (1Н, d, J=18.0 Hz, СН₂-нафтил), 5.76 (1Н, J=18.0 Hz, СН₂-нафтил), 3.36 (1H,d, J₀=7.2Hz, Н₂ нафтил), 6.51 (1Н, t, J₀=7.4 Hz, Н₅ Trp), 6.72 (1Н, d, J₀=7.9 Hz, H₄ Trp), 6.76 (1H, t, J₀=7.5 Hz, H₅ индол), 6.92 (1H, t, J₀=7.5 Hz, H₆ Trp), 7.0 (1H, t, J₀=7.5 Hz, H₆ индол), 7.02 (1H, d, J=2.0 Hz, H₂ индол), 7.09 (1H,d, J=2.0 Hz, H₂ Trp), 7.13 (1H, d, J₀=7.9 Hz, H₄ индол), 7.26(1H, J₀=7.9 Hz, H₇ Trp), 7.27 (1H, t, J₀=8.2 Hz, H₃ нафтил), 7.29 (1H, d, H₇ индол), 7.58-7.64 (2, m, H₆ и H₇ нафтил), 7.88 (1H, d, J₀=8.2 Hz, H₄ нафтил), 7.93 (1H, d, J₀=7.9 Hz, H₈ нафтил), 7.98 (3Н, brs, NH₂ Aib), 8.03 (1H, d, J₀=8.2 Hz, H₅ нафтил), 8.96 (1H, d, J₀=7.9 Hz, NH Trp), 10.75 (1H, brs, NH индол), 10.77 (1H, brs, NH индол Trp).δ (ppm) 1.25 (3H, S, CH ₃ Aib), 1.28 (3H, s, CH ₃ Aib), 2.93 (2H, m,

-CH ₂ -indole), 3.01 (2H, m, CH ₂ -

-indole), 3.30 (1Н, dd, 3J = 14.3 and 5.8 Hz, СН ₂ βTrp), 3.40 (1Н, dd, 3J = 14.3 and 8.8 Hz, CH ₂ βTrp), 5.03 (1Н, m, СН αTrp), 5.62 (1H, d, J = 18.0 Hz, CH ₂ naphthyl), 5.76 (1H, J = 18.0 Hz, CH ₂ naphthyl), 3.36 (1H, d, J ₀ = 7.2Hz, N ₂ naphthyl), 6.51 (1H, t, J ₀ = 7.4 Hz, H ₅ Trp), 6.72 (1H, d, J ₀ = 7.9 Hz, H ₄ Trp), 6.76 (1H, t, J ₀ = 7.5 Hz, H ₅ indole), 6.92 (1H, t, J ₀ = 7.5 Hz, H ₆ Trp), 7.0 (1H, t, J ₀ = 7.5 Hz, H ₆ indole), 7.02 (1H, d, J = 2.0 Hz, H ₂ indole), 7.09 (1H, d, J = 2.0 Hz, H ₂ Trp), 7.13 (1H, d, J ₀ = 7.9 Hz, H ₄ indole), 7.26 (1H, J ₀ = 7.9 Hz, H ₇ Trp), 7.27 ( 1H, t, J ₀ = 8.2 Hz, H ₃ naphthyl), 7.29 (1H, d, H ₇ indole), 7.58-7.64 (2, m, H ₆ and H ₇ naphthyl), 7.88 (1H, d, J ₀ = 8.2 Hz, H ₄ naphthyl), 7.93 (1H, d, J ₀ = 7.9 Hz, H ₈ naphthyl), 7.98 (3H, brs, NH ₂ Aib), 8.03 (1H, d, J ₀ = 8.2 Hz, H ₅ naphthyl), 8.96 (1H, d, J ₀ = 7.9 Hz, NH Trp), 10.75 (1H, brs, NH indole), 10.77 (1H, brs, NH indole Trp).

¹³ C NMR (100 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 22.6 (CH ₂ - CH ₂ -indole), 23.1 (CH ₃ Aib), 23.2 (CH ₃ Aib), 25.3 ( C H ₂ -CH ₂ -indole), 28.8 (CH ₂ βTrp), 43.3 ( CH ₂ naphthyl), 45.3 (CH αTrp)), 56.2 (Cq Aib), 109.4 (C ₃ Trp), 111.2 (C ₇ indole and C ₇ Trp), 112.9 (C ₃ indole), 117.5 (C ₄ Trp) 117.8 (C ₄ indole), 118.0 (C ₅ Trp), 118.1 (C ₅ indole), 120.7 (C ₆ Trp), 120.8 (C ₆ indole), 121.6 (C ₂ naphthyl), 122.5 (C ₂ indole and C ₈ naphthyl), 124.4 (C ₂ Trp), 125.4 (C ₃ naphthyl), 126.3 (C ₆ naphthyl), 126.6 (C ₉ indole, C ₉ Trp and C ₇ naphthyl), 127.9 (C ₄ naphthyl), 128.6 (C ₅ naphthyl), 129.5 (С ₉ naphthyl), 131.4 (С ₁ naphthyl), 133.1 (С ₁₀ naphthyl), 135.9 (С ₈ Trp), 136.1 (С ₈ indole), 154.7 (2Cq triazole), 171.4 (СО Aib) . ESI-MS: measured: m / z 596.4 [M + H] ⁺ / calculated: 595.3 g / mol

Example 4:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 6)

Compound 6 was prepared from BOC- (D) -Trp (10 nmol), (3-methoxyphenyl) methanamine, 3- (1H-indol-3-yl) propanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with general synthesis scheme. The total yield after purification by HPLC was 25%.

¹ N NMR (400 MHz, DMSO-d ⁶ ):

-CH₂-индол), 2.98 (2Н, m, СН₂-СН ₂-индол), 3.33 (1Н, dd, J=14.5, J=6.2, 1Н CH₂ βTrp), 3.40 (1Н, dd, J=14.5, J=8.8, 1Н СН₂ βTrp), 3.66 (3Н, s, ОСН₃), 5.09 (2Н, m, СН₂ мета-метоксибензил), 5.22 (1Н, m, СαН Trp), 6.38 (1Н, d, J=7.5, Н₆ мета-метоксибензил), 6.59 (1Н, s, Н₂ мета-метоксибензил), 6.86 (1Н, t, Н₅ Trp), 6.87 (1Н, d, Н₄ мета-метоксибензил), 6.92 (1Н, t, J=7.5, Н₅ индол), 7.03 (1Н, t, J=7.9, Н₆ Trp), 7.05 (1H, t, H₆ индол), 7.07 (1Н, s, Н₂ индол), 7.11 (1Н, s, Н₂ Trp), 7.18 (1Н, t, Н₅ мета-метоксибензил), 7.19 (1Н, d, Н₄ Trp), 7.31 (1Н, Н₄ индол), 7.32 (2Н, Н₇ Trp, Н₇ индол), 8.00 (2Н, s, NH₂ Aib), 8.96 (1Н, d, J=8.1, NH Trp), 10.78 (1H, s, NH индол), 10.80 (1H, s, NH индол Trp).δ (ppm) 1.28 (3H, s, CH ₃ Aib), 1.30 (3H, s, CH ₃ Aib), 2.92 (2H, m,

-CH ₂ -indole), 2.98 (2Н, m, СН ₂ - СН ₂ -indole), 3.33 (1Н, dd, J = 14.5, J = 6.2, 1Н CH ₂ βTrp), 3.40 (1Н, dd, J = 14.5, J = 8.8, 1H CH ₂ βTrp), 3.66 (3H, s, OCH ₃ ), 5.09 (2H, m, CH ₂ meta-methoxybenzyl), 5.22 (1H, m, СαН Trp), 6.38 (1Н, d , J = 7.5, H ₆ meta-methoxybenzyl), 6.59 (1H, s, H ₂ meta-methoxybenzyl), 6.86 (1H, t, H ₅ Trp), 6.87 (1H, d, H ₄ meta-methoxybenzyl), 6.92 (1H, t, J = 7.5, H ₅ indole), 7.03 (1H, t, J = 7.9, H ₆ Indole), 7.05 (1H, t, H ₆ indole), 7.07 (1H, s, H ₂ indole) 7.11 (1H, s, H ₂ Trp), 7.18 (1H, t, H ₅ meta-methoxybenzyl), 7.19 (1H, d, H ₄ Trp), 7.31 (1H, H ₄ indole), 7.32 (2H, H ₇ Trp, H ₇ indole), 8.00 (2H, s, NH ₂ Aib), 8.96 (1H, d, J = 8.1, NH Trp), 10.78 (1H, s, NH indole), 10.80 (1H, s, NH indole Trp).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

δ (ppm) 22.4 ( CH ₂ -CH ₂ indole), 23.1 (CH ₃ Aib), 23.3 (CH ₃ Aib), 25.4 (CH ₂ - C H ₂ indole), 28.7 (CβTrp), 45.3 (CH ₂ meta methoxybenzyl), 45.4 (CαTrp), 55.0 (OCH ₃ ), 56.3 (Cq Aib), 109.5 (C ₃ Trp), 111.3 (C ₇ Trp, C ₇ indole), 112.0 (C ₂ meta-methoxybenzyl), 113.0 (C ₄ meta-methoxybenzyl, C ₃ indole), 117.8 (C ₄ Trp, C ₆ meta-methoxybenzyl), 118.0 (C ₄ indole), 118.2 (C ₅ indole), 118.3 (C ₅ Trp), 120.8 (C ₆ indole) , 120.9 (C ₆ Trp), 122.4 (C ₂ Indole), 124.3 (C ₂ Trp), 126.7 (C ₉ Indole), 126.9 (C ₉ Trp), 130.0 (C ₅ meta-methoxybenzyl), 136.0 (C ₈ Indole ), 136.1 (C ₈ Trp), 137.2 (C ₁ meta-methoxybenzyl), 154.3 (2Cq triazole), 159.6 (C ₃ meta-methoxybenzyl), 171.4 (CO Aib).

ESI-MS: measured: m / z 576.6 [M + H] ⁺ / calculated: 575.3 g / mol

Example 5:

(R) -N- (1- (4- (3-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 7)

Compound 7 was obtained from BOC- (D) -Trp (10 nmol), (3-methoxyphenyl) methanamine, 2-phenylacetohydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with the general synthesis scheme. The total yield after purification by HPLC was 30%.

¹ N NMR (400 MHz, DMSO-d ⁶ ):

δ (ppm) 1.25 (3H, s, CH ₃ Aib), 1.29 (3H, s, CH ₃ Aib), 3.24 (1H, dd, J = 14.3, J = 5.8, 1H CH ₂ βTrp), 3.38 (1H, dd, J = 14.3, J = 9.1, 1H CH ₂ βTrp), 3.61 (3H, s, meta-OCH ₃ ), 4.04 (2H, m, CH ₂ benzyl), 5.07 (1H, d, J = 17.4, 1H CH ₂ meta-methoxybenzyl), 5.13 (1H, d, J = 17.4, 1H CH ₂ meta-methoxybenzyl), 5.14 (1H, m, CαH Trp), 6.32 (1H, d, J = 7.8, H ₆ meta-methoxybenzyl ), 6.40 (1Н, m, Н ₂ meta-methoxybenzyl), 6.82 (1Н, t, Н ₅ Trp), 6.83 (1Н, d, J = 7.8, Н ₄ meta-methoxybenzyl), 7.01 (1Н, t, J = 8.2, H ₆ Trp), 7.04 (1H, d, J = 8.2, H ₄ Trp), 7.06 (1H, d, J = 2.0, H ₂ Trp), 7.12 (2H, m, H ₂ , H ₆ benzyl ), 7.13 (1H, t, J = 7.9, H ₅ meta-methoxybenzyl), 7.20 (1H, m, H ₄ benzyl), 7.24 (2H, m, H ₃ , H ₅ benzyl), 7.29 (1H, d, J = 8.2, H ₇ Trp), 7.99 (2H, s, NH ₂ Aib), 8.92 (1H, d, J = 8.2, NH Trp), 10.77 (1H, s, NH indol Trp).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

δ (ppm) 23.0 (CH ₃ Aib), 23.3 (CH ₃ Aib), 28.6 (CβTrp), 30.1 (CH ₂ benzyl), 45.2 (Cα Trp), 45.6 (CH ₂ metha methoxybenzyl), 54.9 (meta OCH ₃ ), 56.2 (Cq Aib), 109.4 (C ₃ Trp), 111.2 (C ₇ Trp), 111.7 (C ₂ meta-methoxybenzyl), 113.1 (C ₄ meta-methoxybenzyl), 117.9 (C ₄ Trp, C ₆ meta-methoxybenzyl), 118.2 (C ₅ Trp), 120.8 (C ₆ Trp), 124.3 (C ₂ Trp), 126.6 (C ₄ benzyl), 126.8 (C ₉ Trp), 128.3 (C ₃ , C ₅ benzyl), 128.4 (C ₂ , C ₆ benzyl), 129.9 (C ₅ meta-methoxybenzyl), 135.9 (C ₁ benzyl, C ₈ Trp), 137.0 (C ₁ meta-methoxybenzyl), 153.5 (Cq triazole), 154.8 (Cq triazole) 159.5 (C ₃ meta-methoxybenzyl); 171.3 (CO Aib).

ESI-MS: measured: m / z 523.3 [M + H] ⁺ / calculated: 522.3 g / mol

Example 6:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 8)

Compound 8 was obtained from BOC- (D) -Trp (10 nmol), phenylmethanamine, 3- (1H-indol-3-yl) propanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with the general synthesis scheme. The total yield after purification by HPLC was 45%.

¹ N NMR (400 MHz, DMSO-d ⁶ ):

δ (ppm) 1.29 (3H, s, CH ₃ Aib), 1.30 (3H, s, CH ₃ Aib), 2.88 (2H, m, CH ₂ -CH ₂ -indole), 2.97 (2H, m, CH ₂ - CH ₂ -indole), 3.37 (2H, m, CH ₂ βTrp), 5.11 (2H, s, CH ₂ benzyl), 5.21 (1H, m, CαH Trp), 6.86 (1H, t, J = 7.4, H ₅ Trp), 6.88 (2H, H ₂ , H ₆ benzyl), 6.92 (1H, t, J = 7.6, H ₅ indole), 7.03 (1H, t, J = 7.6, H ₆ Trp), 7.05 (2H, H ₆ indole, H ₂ indole), 7.09 (1H, d, J = 1.8, H ₂ Trp), 7.17 (1H, d, J = 7.9, H ₄ Trp), 7.26 (2H, H ₃ , H ₅ benzyl), 7.27 (1H, H ₄ benzyl), 7.30 (1H, H ₄ indole), 7.32 (2H, H ₇ Trp, H ₇ indole), 8.03 (2H, brs, NH ₂ Aib), 8.95 (1H, d, J = 8.1, NH Trp), 10.77 (1H, s, NH indole), 10.81 (1H, s, NH indole Trp).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

-CH₂ индол), 28.7 (CβTrp), 45.3 (CαTrp, СН ₂-бензил), 56.3 (Cq Aib), 109.5 (C₃ Trp), 111.3 (C₇ Trp, C₇ индол), 113.0 (C₃ индол), 117.8 (C₄ Trp), 118.0 (C₄ индол), 118.2 (C₅ индол), 118.3 (C₅ Trp), 120.9 (C₆ Trp, C₆ индол), 122.4 (C₂ индол), 124.2 (C₂ Trp), 125.9 (C₂, C₆ бензил), 126.7 (C₉ индол), 126.9 (C₉ Trp), 127.6 (C₄ бензил), 128.8 (C₃, C₅ бензил), 135.7 (С₁ бензил), 136.0 (C₈ Trp), 136.1 (C₈ индол), 154.3 (Cq триазол), 154.5 (Cq триазол), 171.4 (CO Aib).δ (ppm) 22.4 (CH ₂ - C H ₂ indole), 23.1 (CH ₃ Aib), 23.3 (CH ₃ Aib), 25.4 (

-CH ₂ indole), 28.7 (CβTrp), 45.3 (CαTrp, CH ₂ -benzyl), 56.3 (Cq Aib), 109.5 (C ₃ Trp), 111.3 (C ₇ Trp, C ₇ indole), 113.0 (C ₃ indole ), 117.8 (C ₄ Trp), 118.0 (C ₄ indole), 118.2 (C ₅ indole), 118.3 (C ₅ Trp), 120.9 (C ₆ Trp, C ₆ indole), 122.4 (C ₂ indole), 124.2 ( C ₂ Trp), 125.9 (C ₂ , C ₆ benzyl), 126.7 (C ₉ indol), 126.9 (C ₉ Trp), 127.6 (C ₄ benzyl), 128.8 (C ₃ , C ₅ benzyl), 135.7 (C ₁ benzyl), 136.0 (C ₈ Trp), 136.1 (C ₈ indole), 154.3 (Cq triazole), 154.5 (Cq triazole), 171.4 (CO Aib).

ESI-MS: measured: m / z 546.3 [M + H] ⁺ / calculated: 545.3 g / mol

Example 7

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 9)

Compound 9 was prepared from BOC- (D) -Trp (10 nmol), phenylmethanamine, 4- (1H-indol-3-yl) butanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with the general synthesis scheme. The total yield after purification by HPLC was 38%.

¹ H NMR (400 MHz, DMSO-d ⁶ ):

-CH₂-индол), 2.61 (2H, m, СН ₂-СН₂-СН₂-индол), 2.69 (2H, m, СН₂-СН₂-СН ₂-индол), 3.37 (2H, m, CH₂ βTrp), 5.09 (2H, s, CH₂ бензил), 5.20 (1H, m, CαH Trp), 6.85 (3H, m, H₂, H₆ бензил, H₅ Trp), 6.94 (1H, t, J=7.5, H₅ индол), 7.01 (1H, s, H₂ индол), 7.02 (1H, 1, J=7.8, H₆ Trp), 7.05 (1H, t, J=8, H₆ индол), 7.08 (1H, d, J=2.0, H₂ Trp), 7.14 (1H, d, J=8.0, H₄Trp), 7.25 (3H, m, H₃, H₄, H₅ бензил), 7.31 (1H, d, J=8.0, H₇ Trp), 7.32 (1H, d, J=8.0, H₇ индол), 7.42 (1H, d, J=7.8, H₄ индол), 8.03 (2H, s, NH₂ Aib), 8.95 (1H, d, J=8.1, NH Trp), 10.73 (1H, s, NH индол), 10.80 (1H, d, J=2.0, NH индол Trp).δ (ppm) 1.29 (3H, s, CH ₃ Aib), 1.31 (3H, s, CH ₃ Aib), 1.90 (2H, m, CH ₂ -

-CH ₂ -indole), 2.61 (2H, m, CH ₂ -CH ₂ -CH ₂ -indole), 2.69 (2H, m, CH ₂ -CH ₂ - CH ₂ -indole), 3.37 (2H, m, CH ₂ βTrp), 5.09 (2H, s, CH ₂ benzyl), 5.20 (1H, m, CαH Trp), 6.85 (3H, m, H ₂ , H ₆ benzyl, H ₅ Trp), 6.94 (1H, t, J = 7.5, H ₅ indole), 7.01 (1H, s, H ₂ indole), 7.02 (1H, 1, J = 7.8, H ₆ Trp), 7.05 (1H, t, J = 8, H ₆ indole), 7.08 (1H, d, J = 2.0, H ₂ Trp), 7.14 (1H, d, J = 8.0, H ₄ Trp), 7.25 (3H, m, H ₃ , H ₄ , H ₅ benzyl), 7.31 (1H, d, J = 8.0, H ₇ Trp), 7.32 (1H, d, J = 8.0, H ₇ indole), 7.42 (1H, d, J = 7.8, H ₄ indole), 8.03 (2H, s, NH ₂ Aib ), 8.95 (1H, d, J = 8.1, NH Trp), 10.73 (1H, s, NH indol), 10.80 (1H, d, J = 2.0, NH indol Trp).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

-СН₂-СН₂-индол), 24.1 (СН₂-СН₂-СН₂-индол), 27.2 (СН₂-СН₂-СН₂-индол), 28.7 (СβTrp), 45.4 (CαTrp), 45.5 (СН₂ бензил), 56.3 (Cq Aib), 109.4 (С₃ Trp), 111.3 (С₇ Trp, С₇ индол), 113.6 (С₃ индол), 117.8 (С₄Trp), 118.0 (С₅ индол), 118.2 (С₄ индол), 118.3 (С₅Trp), 120.8 (С₆ индол, С₆ Trp), 122.2 (С₂ индол), 124.3 (С₂ Trp), 125.9 (С₂, С₆ бензил), 126.8 (С₉ Trp), 127.0 (С₉ индол), 127.7 (С₄ бензил), 128.7 (С₃, С₅ бензил), 135.5 (С₁ бензил), 136.0 (С₈ Trp), 136.2 (С₈ индол), 154.3 (Cq триазол), 154.7 (Cq триазол), 171.4 (СО Aib).δ (ppm) 23.1 (CH ₃ Aib), 23.3 (CH ₃ Aib), 23.8 (

-CH ₂ -CH ₂ -indole), 24.1 (CH ₂ -CH ₂ - С Н ₂ -indole), 27.2 (СН ₂ - С Н ₂ -CH ₂ -indole), 28.7 (СβTrp), 45.4 (CαTrp), 45.5 (CH ₂ benzyl), 56.3 (Cq Aib), 109.4 (C ₃ Trp), 111.3 (C ₇ Trp, C ₇ indole), 113.6 (C ₃ Indole), 117.8 (C ₄ Trp), 118.0 (C ₅ indole ), 118.2 (C ₄ indole), 118.3 (C ₅ Trp), 120.8 (C ₆ indole, C ₆ Trp), 122.2 (C ₂ indole), 124.3 (C ₂ Trp), 125.9 (C ₂ , C ₆ benzyl) 126.8 (С ₉ Trp), 127.0 (С ₉ indole), 127.7 (С ₄ benzyl), 128.7 (С ₃ , С ₅ benzyl), 135.5 (С ₁ benzyl), 136.0 (С ₈ Trp), 136.2 (С ₈ indole), 154.3 (Cq triazole), 154.7 (Cq triazole), 171.4 (CO Aib).

ESI-MS: measured: m / z 560.4 [M + H] ⁺ / calculated: 559.3 g / mol

Example 8:

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) octyl) -2-amino-2-methylpropanamide (Compound 10)

Compound 10 was prepared from BOC- (D) -Trp (10 nmol) (3-methoxyphenyl) methanamine, 4- (1H-indol-3-yl) butanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with the general synthesis scheme. The total yield after purification by HPLC was 25%.

¹ N NMR (400 MHz, DMSO-d ⁶ ):

-СН₂-индол), 2.62 (2Н, m, СН₂-СН₂-СН₂-индол), 2.68 (2Н, m, СН₂-СН₂-СН ₂-индол), 3.24 (1Н, dd, J=14.5, J=5.8, 1Н СН₂ βTrp), 3.39 (1Н, dd, J=14.5, J=9.0, 1Н СН₂ βTrp), 3.66 (3Н, s, мета-ОСН₃), 5.07 (2Н, s, СН₂ мета-метоксибензил), 5.18 (1Н, m, СαН Trp), 6.35 (1Н, d, J=7.5, Н₆ мета-метоксибензил), 6.54 (1Н, bs, Н₂ мета-метоксибензил), 6.84 (1Н, t, J=7.5, Н₅ Trp), 6.87 (1Н, dd, J=8.0, J=2.1, H₄ мета-метоксибензил), 6.94 (1Н, t, J=7.3, Н₅ индол), 7.02 (1Н, t, Н₆ Trp), 7.02 (1Н, s, Н₂ индол), 7.05 (1Н, t, J=7.8, Н₆ индол), 7.08 (1Н, d, J=2.1, Н₂ Trp), 7.13 (1Н, d, J=8.1, Н₄ Trp), 7.17 (1Н, t, J=8.1, H₅ мета-метоксибензил), 7.30 (1Н, d, Н₇ Trp), 7.32 (1Н, d, J=8, Н₇ индол), 7.42 (1Н, d, J=7.6, Н₄ индол), 7.98 (2Н, s, NH₂ Aib), 8.93 (1Н, d, J=8.2, NH Trp), 10.71 (1H, s, NH индол), 10.77 (1H, s, NH индол Trp).δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.30 (3H, s, CH ₃ Aib), 1.92 (2H, m, CH ₂ -

-CH ₂ -indole), 2.62 (2H, m, CH ₂ -CH ₂ -CH ₂ -indole), 2.68 (2H, m, CH ₂ -CH ₂ - CH ₂ -indole), 3.24 (1H, dd, J = 14.5, J = 5.8, 1H CH ₂ βTrp), 3.39 (1H, dd, J = 14.5, J = 9.0, 1H CH ₂ βTrp), 3.66 (3H, s, meta-OCH ₃ ), 5.07 (2H, s , CH ₂ meta-methoxybenzyl), 5.18 (1Н, m, СαН Trp), 6.35 (1Н, d, J = 7.5, Н ₆ meta-methoxybenzyl), 6.54 (1Н, bs, Н ₂ meta-methoxybenzyl), 6.84 ( 1H, t, J = 7.5, H ₅ Trp), 6.87 (1H, dd, J = 8.0, J = 2.1, H ₄ meta-methoxybenzyl), 6.94 (1H, t, J = 7.3, H ₅ indole), 7.02 (1Н, t, Н ₆ Trp), 7.02 (1Н, s, Н ₂ indole), 7.05 (1Н, t, J = 7.8, Н ₆ indole), 7.08 (1Н, d, J = 2.1, Н ₂ Trp) 7.13 (1H, d, J = 8.1, H ₄ Trp), 7.17 (1H, t, J = 8.1, H ₅ meta-methoxybenzyl), 7.30 (1H, d, H ₇ Trp), 7.32 (1H, d, J = 8, H ₇ indole), 7.42 (1H, d, J = 7.6, H ₄ indole), 7.98 (2H, s, NH ₂ Aib), 8.93 (1H, d, J = 8.2, NH Trp), 10.71 (1H, s, NH indole), 10.77 (1H, s, NH indole Trp).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

-индол), 27.4 (СН₂-

-СН₂-индол), 28.8 (CβTrp), 45.2 (СН₂-мета-метоксибензил), 45.4 (CαTrp), 55.1 (мета-ОСН₃), 56.3 (Cq Aib), 109.5 (C₃ Trp), 111.3 (C₇ Trp, C₇ индол), 111.8 (C₂ мета-метоксибензил), 113.0 (C₄ мета-метоксибензил), 113.8 (C₃ индол), 117.8 (C₆ мета-метоксибензил), 117.9 (C₄ Trp), 118.1 (C₅ индол), 118.2 (C₅ Trp, C₄ индол), 120.8 (C₆ Trp), 120.9 (C₆ индол), 122.2 (C₂ индол), 124.3 (C₂ Trp), 126.8 (C₉ Trp), 127.0 (C₉ индол), 130.0 (С₅ мета-метоксибензил), 136.0 (С₈ Trp), 136.2 (С₈ индол), 137.4 (С₁ мета-метоксибензил), 154.3 (Cq триазол), 154.6 (Cq триазол), 159.7 (С₃ мета-метоксибензил), 171.4 (СО Aib).δ (ppm) 23.1 (CH ₃ Aib), 23.3 (CH ₃ Aib), 23.9 ( C H ₂ -CH ₂ -CH ₂ -indole), 24.3 (CH ₂ -CH ₂ -

-indole), 27.4 (CH ₂ -

-CH ₂ -indole), 28.8 (CβTrp), 45.2 ( С Н ₂ -meta-methoxybenzyl), 45.4 (CαTrp), 55.1 (meta-OCH ₃ ), 56.3 (Cq Aib), 109.5 (C ₃ Trp), 111.3 (C ₇ Trp, C ₇ indole), 111.8 (C ₂ meta-methoxybenzyl), 113.0 (C ₄ meta-methoxybenzyl), 113.8 (C ₃ indole), 117.8 (C ₆ meta-methoxybenzyl), 117.9 (C ₄ Trp) , 118.1 (C ₅ indole), 118.2 (C ₅ Trp, C ₄ indole), 120.8 (C ₆ Trp), 120.9 (C ₆ indole), 122.2 (C ₂ indole), 124.3 (C ₂ Trp), 126.8 (C ₉ Trp), 127.0 (C ₉ indole), 130.0 (C ₅ meta-methoxybenzyl), 136.0 (C ₈ Trp), 136.2 (C ₈ indole), 137.4 (C ₁ meta-methoxybenzyl), 154.3 (Cq triazole), 154.6 (Cq triazole), 159.7 (C ₃ meta-methoxybenzyl), 171.4 (CO Aib).

ESI-MS: measured: m / z 590.3 [M + H] ⁺ / calculated: 589.3 g / mol

Example 9:

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 11)

Compound 11 was prepared from BOC- (D) -Trp (10 nmol), naphthalen-1-ylmethanamine, 4- (1H-indol-3-yl) butanhydrazide and BOC-2-amino-2-methylpropanoic acid according to the general scheme synthesis. The total yield after purification by HPLC was 22%.

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.20 (3H, s, CH ₃ Aib), 1.25 (3H, s, CH ₃ Aib), 1.93 (2H, m, CH ₂ -CH ₂ -C H ₂ -indole), 2.66 (4H, m , С Н ₂ -CH ₂ -С Н ₂ -indole), 3.25 (1Н, dd, J = 14 Hz and 5 Hz, CH ₂ βTrp), 3.40 (1H, dd, J = 14 Hz and 9 Hz, CH ₂ βTrp), 4.95 (1H, m, CH βTrp), 5.66 (1H, d, J = 18 Hz, CH ₂ naphthyl), 5.81 (1H, d, J = 18 Hz, CH ₂ naphthyl), 6.37 (1H , d, J ₀ = 7 Hz, H ₂ naphthyl), 6.43 (1H, t, J ₀ = 7 Hz, H ₅ Trp), 6.59 (1H, d, J ₀ = 8 Hz, H ₄ Trp), 6.86 ( 3H, m, H ₅ and H ₆ indole, H ₆ Trp), 6.95 (1H, d, J = 2 Hz, H ₂ indole), 7.00 (1H, d, J ₀ = 8 Hz, H ₄ indole), 7.06 (1H, d, J = 2 Hz, H ₂ Trp), 7.20-7.33 (4H, m, H ₄ and H ₇ indole, H ₇ Trp, H ₃ naphthyl), 7.60 (2H, m, H ₆ and H ₇ naphthyl), 7.87 (1H, d, J ₀ = 8 Hz, H ₄ naphthyl), 7.99 (5H, m, NH ₂ Aib, H ₅ and H ₈ naphthyl), 8.95 (1H, d, J = 8 Hz, NH amide), 10.70 (1H, s, NH indol), 10.77 (1H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.5 (CH ₃ Aib), 23.6 (CH ₃ Aib), 24.1 (CH ₂ -CH ₂ -CH ₂ -indole), 24.5 (CH ₂ -CH ₂ - C H ₂ indole), 27.6 (CH ₂ - С H ₂ -CH ₂ -indole), 29.1 (СН ₂ βTrp), 44.1 ( С Н _2- naphthyl), 45.7 (CH αTrp), 56.7 (Cq Aib), 109.7 (C ₃ Trp), 111.7 (C ₇ indole and C ₇ Trp), 113.9 (C ₃ indole), 117.9 (C ₄ Trp), 118.5 (C ₄ indole, C ₅ Trp), 118.6 (C ₅ indole), 121.1 (C ₆ Trp), 121.2 (C ₆ indole), 122.1 (C ₂ naphthyl), 122.7 (C ₂ indole), 122.9 (C ₈ naphthyl), 125.0 (C ₂ Trp), 125.9 (C ₃ naphthyl), 126.8 (C ₆ naphthyl), 127.0 (C ₉ indole), 127.1 (C ₇ naphthyl), 127.4 (C ₉ Trp), 128.5 (C ₄ naphthyl), 129.2 (C ₅ naphthyl), 129.9 (C ₉ naphthyl), 131.6 (C ₁ naphthyl), 133.6 (C ₁₀ naphthyl) ), 136.4 (C ₈ Trp), 136.7 (C ₈ indole), 155.4 (Cqs triazole), 171.9 (CO Aib).

ESI-MS: measured: m / z 610.3 [M + H] ⁺ / calculated: 609.3 g / mol

Example 10:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 12)

Compound 12 was obtained from BOC- (D) -Trp (10 nmol), (4-methoxyphenyl) methanamine, 3- (1H-indol-3-yl) propanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with general synthesis scheme. The total yield after purification by HPLC was 28%.

¹ N NMR (400 MHz, DMSO-d ⁶ ):

-СН₂-индол), 2.97 (2Н, m, СН₂-

-индол). 3.37 (2Н, d, СН₂ βTrp), 3.71 (3Н, s, ОСН₃), 5.02 (2Н, s, СН₂ пара-метоксибензил), 5.23 (1Н, m, CαH Trp), 6.78 (4Н, m, СНаr пара-метоксибензил), 6.87 (1Н, t, J=7.5, H₅Trp), 6.93 (1Н, t, J=7.5, H₅ индол), 7.03 (1Н, t, Н₆ Trp), 7.05 (1Н, t, Н₆ индол), 7.07 (1Н, s, Н₂ индол), 7.09 (1Н, s, H₂ Trp), 7.21 (1H, d, J=8, H₄ Trp), 7.32 (3Н, H₄ индол, H₇ Trp, H₇ индол), 8.02 (2H, s, NH₂ Aib), 8.97 (1H, d, J=8.1, NH Trp), 10.77 (1H, s, NH индол), 10.80 (1H, s, NH индол Trp).δ (ppm) 1.30 (3H, s, CH ₃ Aib), 1.33 (3H, s, CH ₃ Aib), 2.91 (2H, m,

-CH ₂ -indole), 2.97 (2H, m, CH ₂ -

-indole). 3.37 (2H, d, CH ₂ βTrp), 3.71 (3H, s, OCH ₃ ), 5.02 (2H, s, CH ₂ para-methoxybenzyl), 5.23 (1H, m, CαH Trp), 6.78 (4H, m, CHAR para-methoxybenzyl), 6.87 (1H, t, J = 7.5, H ₅ Trp), 6.93 (1H, t, J = 7.5, H ₅ indole), 7.03 (1H, t, H ₆ Trp), 7.05 (1H , t, H ₆ indole), 7.07 (1H, s, H ₂ indole), 7.09 (1H, s, H ₂ Trp), 7.21 (1H, d, J = 8, H ₄ Trp), 7.32 (3H, H ₄ indole, H ₇ Trp, H ₇ indole), 8.02 (2H, s, NH ₂ Aib), 8.97 (1H, d, J = 8.1, NH Trp), 10.77 (1H, s, NH indole), 10.80 (1H , s, NH indole Trp).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

-СН₂-индол), 23.1 (CH₃ Aib), 23.4 (CH₃ Aib), 25.5 (CH₂-CH₂-индол), 28.9 (CαTrp), 44.9 (CH₂ пара-метоксибензил), 45.3 (CαTrp), 55.0 (OCH₃), 56.3 (Cq Aib), 109.5 (C₃ Trp), 111.3 (C₇ Trp, C₇ индол), 113.0 (C₃ индол), 114.1 (C₃, C₅ пара-метоксибензил), 117.9 (C₄ Trp), 118.0 (C₄ индол), 118.2(C₅ индол), 118.3 (C₅ Trp), 120.9 (C₆ индол, C₆ Trp), 122.0 (C₂ индол), 124.4 (C₂ Trp), 126.7 (C₉ индол), 126.9 (C₉Trp), 127.3 (C₂, C₆ пара-метоксибензил), 127.4 (С₁ пара-метоксибензил), 135.9 (C₈ Trp), 136.1 (C₈ индол), 154.2 (Cq триазол), 154.5 (Cq триазол), 158.4 C₄ пара-метоксибензил), 171.4 (CO Aib). ESI-MS: измеренное: m/z 576.3 [М+Н]⁺/ рассчитанное: 575.3 г/мольδ (ppm) 22.4 (

-CH ₂ -indole), 23.1 (CH ₃ Aib), 23.4 (CH ₃ Aib), 25.5 (CH ₂ -CH ₂ -indole), 28.9 (CαTrp), 44.9 (CH ₂ para-methoxybenzyl), 45.3 (CαTrp) 55.0 (OCH ₃ ), 56.3 (Cq Aib), 109.5 (C ₃ Trp), 111.3 (C ₇ Trp, C ₇ indole), 113.0 (C ₃ indole), 114.1 (C ₃ , C ₅ para-methoxybenzyl), 117.9 (C ₄ Trp), 118.0 (C ₄ indole), 118.2 (C ₅ indole), 118.3 (C ₅ Trp), 120.9 (C ₆ indole, C ₆ Trp), 122.0 (C ₂ indole), 124.4 (C ₂ Trp), 126.7 (C ₉ indole), 126.9 (C ₉ Trp), 127.3 (C ₂ , C ₆ para-methoxybenzyl), 127.4 (C ₁ para-methoxybenzyl), 135.9 (C ₈ Trp), 136.1 (C ₈ indole ), 154.2 (Cq triazole), 154.5 (Cq triazole), 158.4 C ₄ para-methoxybenzyl), 171.4 (CO Aib). ESI-MS: measured: m / z 576.3 [M + H] ⁺ / calculated: 575.3 g / mol

Example 11:

(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 13)

Compound 13 was prepared from BOC- (D) -Trp (10 nmol), (4-methoxyphenyl) methanamine, 2-phenylacetohydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with the general synthesis scheme. The total yield after purification by HPLC was 37%.

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-пара-метоксибензил), 5.12 (1 H, m, CH αTrp)), 6.67 (4H, m, CHar пара-метоксибензил), 6.80 (1 H, 1, J₀=8 Hz, H₅ Trp), 6.98 (1 H, t, J₀=8 Hz, H₆ Trp), 7.02-7.06 (4H, m, H₂ и H₆ бензил, H₂ и H₄ Trp), 7.12-7.25 (3H, m, H₃, H₄ и H₅ бензил), 7.26 (1 H, d, J₀=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib), 8.92 (1 H, d, J=8 Hz, NH Trp), 10.77 (1 H, s, NH индол Trp).δ (ppm) 1.24 (3H, s, CH ₃ Aib), 1.28 (3H, s, CH ₃ Aib), 3.26 (1H, dd, ³ J = 14 Hz and 6 Hz, CH ₂ βTrp), 3.31 (1 H , dd, 3J = 14 Hz and 9 Hz, CH ₂ βTrp), 3.67 (3H, s, OCH ₃ ), 3.99 (2H, s, CH ₂ -benzyl), 4.99 (2H, s,

-para-methoxybenzyl), 5.12 (1 H, m, CH αTrp)), 6.67 (4H, m, CHar para-methoxybenzyl), 6.80 (1 H, 1, J ₀ = 8 Hz, H ₅ Trp), 6.98 ( 1 H, t, J ₀ = 8 Hz, H ₆ Trp), 7.02-7.06 (4H, m, H ₂ and H ₆ benzyl, H ₂ and H ₄ Trp), 7.12-7.25 (3H, m, H ₃ , H ₄ and H ₅ benzyl), 7.26 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 8.01 (3H, brs, NH ₂ Aib), 8.92 (1 H, d, J = 8 Hz, NH Trp), 10.77 (1 H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.5 (CH ₃ Aib), 23.7 (CH ₃ Aib), 29.1 (CH ₂ βTrp), 30.6 ( C H ₂ -benzyl), 45.7 ( C H ₂ -paramethoxybenzyl), 45.7 (CH αTrp) ), 55.5 (OCH ₃ ), 56.7 (Cq Aib), 109.8 (C ₃ Trp), 111.7 (C ₇ Trp), 114.5 (C ₃ and C ₅ para-methoxybenzyl), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.8 (C ₂ Trp), 127.1 (C ₂ and C ₆ benzyl), 127.3 (C ₉ Trp), 127.6 (C ₁ para-methoxybenzyl), 127.8 (C ₂ and C ₆ para-methoxybenzyl), 128.8 (C ₃ , C ₄ and C ₅ para-methoxybenzyl), 136.3 (C ₁ benzyl), 136.4 (C ₈ Trp), 153.8 (Cq triazole), 155.2 (Cq triazole), 159.1 (C ₄ para-methoxybenzyl), 171.9 (CO Aib). ESI-MS: measured: m / z 524.1 [M + H] ₊ / calculated: 522.3 g / mol.

Example 12:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 15)

Compound 15 was prepared from BOC- (D) -Trp (10 nmol), hexan-1-amine, 3- (1H-indol-3-yl) propanhydrazide and BOC-2-amino-2-methylpropanoic acid according to the general scheme synthesis. The total yield after purification by HPLC was 28%.

¹ N NMR (400 MHz, DMSO-d ⁶ ):

), 1.01 (4H, m, 2СН₂), 1.11 (2Н, m,

-СН₃), 1.14 (1Н, m, 1 Н N-CH₂-

), 1.33 (1 Н, m, 1 Н N-CH₂-

), 1-40 (3Н, s, СН₃ Aib), 1.42 (3Н, s, СН₃ Aib), 3.05 (2Н, m, СН ₂-СН₂-индол), 3.10 (2Н, m, СН₂-СН ₂-индол), 3.37 (1 Н, dd, J=14.2, J=7.6, 1H CH₂ βTrp), 3.44 (1 Н, dd, J=14.2, J=7.6, 1 H CH₂ βTrр), 3.58 (1 H, m, 1 H N-CH₂), 3.71 (1 H, m, 1H N-CH₂), 5.21 (1 H, m, CαH Trp), 6.96 (1 H, H₅ Trp), 6.97 (1 H, H₅ индол), 7.06 (2H, H₆ Trp, H₆ индол), 7.09 (1 H, s, H₂ Trp), 7.13 (1H, s, H₂ индол), 7.34 (2H, H₇ Trp, H₇ индол), 7.48 (1 H, d, H₄ индол), 7.50 (1 H, H₄ Trp), 8.14 (2H, s, NH₂ Aib), 9.08 (1 H, d, J=7.8, NH Trp), 10.84 (1H, s, NH индол), 10.88 (1 H, s, NH индол Trp).δ (ppm) 0.77 (3H, t, J = 7.2 (CH ₂ ) ₅ -

), 1.01 (4H, m, 2CH ₂ ), 1.11 (2H, m,

-CH ₃ ), 1.14 (1H, m, 1 H N-CH ₂ -

), 1.33 (1 N, m, 1 N N-CH ₂ -

), 1-40 (3H, s, CH ₃ Aib), 1.42 (3H, s, CH ₃ Aib), 3.05 (2H, m, CH ₂ -CH ₂ -indole), 3.10 (2H, m, CH ₂ - CH ₂ -indole), 3.37 (1 N, dd, J = 14.2, J = 7.6, 1H CH ₂ βTrp), 3.44 (1 N, dd, J = 14.2, J = 7.6, 1 H CH ₂ βTrp), 3.58 (1 H, m, 1 H N-CH ₂ ), 3.71 (1 H, m, 1H N-CH ₂ ), 5.21 (1 H, m, CαH Trp), 6.96 (1 H, H ₅ Trp), 6.97 (1 H, H ₅ indole), 7.06 (2H, H ₆ Trp, H ₆ indole), 7.09 (1 H, s, H ₂ Trp), 7.13 (1H, s, H ₂ indole), 7.34 (2H, H ₇ Trp, H ₇ indole), 7.48 (1 H, d, H ₄ indole), 7.50 (1 H, H ₄ Trp), 8.14 (2H, s, NH ₂ Aib), 9.08 (1 H, d, J = 7.8, NH Trp), 10.84 (1H, s, NH indole), 10.88 (1 H, s, NH indole Trp).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

δ (ppm) 13.7 (CH ₂ ) ₅ - CH ₃ ), 21.7 ( CH ₂ -CH ₃ ), 22.4 (CH ₂ - CH ₂ -indole), 23.1 (CH ₃ Aib), 23.3 (CH ₃ Aib), 25.1 ( CH ₂ -CH ₂ -indole), 25.5 (CH ₃ -CH ₂ -CH ₂ - CH ₂ ), 29.1 (Cβ Trp), 29.3 (N-CH ₂ - CH ₂ ), 30.4 (CH ₃ -CH ₂ - CH ₂ ), 42.6 (N- CH ₂ -CH ₂ ), 45.6 (Cα rp), 56.3 (Cq Aib), 109.2 (C ₃ Trp), 111.4-111.5 (C ₇ Trp, C ₇ indole), 112.8 (C ₃ indol), 117.7 (C ₄ Trp), 118.0 (C ₅ indol), 118.2 (C ₄ indol), 118.4 (C ₅ Trp), 120.9 (C ₆ indol, C ₆ Trp), 122.6 (C ₂ indol), 124.3 (C ₂ Trp), 126.8 (C ₉ Trp), 126.9 (C ₉ indole), 136.0 (C ₈ Trp), 136.2 (C ₈ indole), 154.0 (Cq triazole), 154.1 (Cq triazole), 171.4 (CO Aib). ESI-MS: measured: m / z 540.3 [M + H] ⁺ / calculated: 539.3 g / mol.

Example 13:

(S) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 18)

Compound 18 was prepared from BOC- (L) -Trp (10 nmol), (2,4-dimethoxyphenyl) methanamine, 3- (1H-indol-3-yl) propanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with the general scheme of synthesis. The total yield after purification by HPLC was 30%.

¹ H NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.31 (3H, s, CH ₃ Aib), 2.89 (2H, m, С Н ₂ -CH ₂ -indole), 2.93 (2H, m, СН ₂ -C H ₂ -indole), 3.27 (2H, m, CH ₂ βTrp), 3.62 (3H, s, O-OCH ₃ ), 3.68 (3H, s, para-OCH ₃ ), 4.89 (1H, d, ³ J = 17Hz, CH ₂ -o, para-dimethoxybenzyl), 5.06 (1H, d, ³ J = 17Hz, CH ₂ -o, para-dimethoxybenzyl), 5.18 (1 H, m, CH αTrp), 6.27 (1 H , dd, J ₀ = 8Hz and J _p = 2Hz, H ₅ about, para-dimethoxybenzyl), 6.40 (1H, d, 8Hz, H ₆ about, para-dimethoxybenzyl), 6.56 (1H, d, J _p = 2Hz, H ₃ о, para-dimethoxybenzyl), 6.83 (1 H, t, J ₀ = 7Hz, H ₅ Trp), 6.90 (1 H, 1, J ₀ = 7 Hz, H ₅ indole), 7.02 (1 H, 1 , H ₆ Trp), 7.04 (1 H, t, H ₆ indole), 7.07 (1H s, H ₂ indole), 7.08 (1 H, s, H ₂ Trp), 7.12 (1H, d , J ₀ = 8 Hz, H ₄ Trp), 7.29 (3H, H ₄ and H ₇ indole, H ₇ Trp), 8.00 (3H, brs, NH ₂ Aib), 8.93 (1 H, d, J = 8 Hz, NH amide), 10.76 (1 H, s, NH indole), 10.79 (1 H, s, NH and ndol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 22.9 (CH ₂ - C H ₂ -indole), 23.6 (CH ₃ Aib), 23.7 (CH ₃ Aib), 25.8 ( C H ₂ -CH ₂ -indole), 29.2 (CH ₂ βTrp), 41.4 ( C H ₂ -o, para-dimethoxybenzyl), 45.7 (Cα Trp), 55.7 (para-OCH ₃ ), 55.9 (O-OCH ₃ ), 56.7 (Cq Aib), 99.0 (C ₃ about, para-dimethoxybenzyl) 105.1 (C ₅ about, para-dimethoxybenzyl), 109.9 (C ₃ Trp), 111.8 (C ₇ Trp, C ₇ indole), 113.4 (C ₃ indole), 115.6 (C ₁ about, para-dimethoxybenzyl), 118.3 ( C ₄ indole), 118.4 (C ₄ Trp), 118.6 (C ₅ Trp, C ₅ indole), 121.3 (C ₆ Trp, C ₆ indole), 122.6 (C ₂ indole), 124.4 (C ₂ Trp), 127.2 ( C ₉ indole), 127.3 (C ₉ Trp), 128.0 (C ₆ about, para-dimethoxybenzyl), 136.4 (C ₈ Trp), 136.6 (C ₈ indole), 155.0 (2Cq triazole), 157.7 (C ₂ about, pair -dimethoxybenzyl), 160.9 (C ₄ about, para-dimethoxybenzyl), 171.6 (CO Aib).

ESI-MS: measured: m / z 606.2 [M + H] ⁺ / calculated: 605.3 g / mol.

Example 14:

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 23)

Compound 23 was obtained from BOC- (D) -Trp (10 nmol), (4-methoxyphenyl) methanamine, 4- (1H-indol-3-yl) butanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with general synthesis scheme. The total yield after purification by HPLC was 25%.

¹ N NMR (300 MHz, DMSO-d ₆ , 300 K):

СН₂-индол), 2.58 (2Н, m, СН ₂СН₂СН₂-индол), 2.65 (2Н, m, СН₂СН₂ СН ₂-индол), 3.34 (2Н, d, ³J=7 Hz, СН₂ βTrp), 3.67 (3Н, s, ОСН₃), 4.96 (2Н, s, СН₂-пара-метоксибензил), 5.19 (1 Н, m, СН αTrp), 6.71 (4Н, s, СН ar пара-метоксибензил), 6.89 (1 Н, t, J₀=7 Hz, Н₅ Trp), 6.92 (1Н, t, J₀=7 Hz, H₅ индол), 7.02 (1 H, s, H₂ индол), 7.05 (1H, s, H₂ Trp), 7.14 (1 H, d, J₀=8 Hz, H₄ Trp), 7.33 (3Н, H₄ индол, H₇ Trp, H₇ индол), 8.02 (3Н, brs, NH₂ Aib), 7.90 (1H, d, J=8 Hz, NH амид), 10.73 (1 H, s, NH индол), 10.79 (1 H, s, NH индол Trp).δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.30 (3H, s, CH ₃ Aib), 1.84 (2H, m, CH ₂

CH ₂ -indole), 2.58 (2H, m, CH ₂ CH ₂ CH ₂ -indole), 2.65 (2Н, m, CH ₂ CH ₂ CH ₂ -indole), 3.34 (2Н, d, ³ J = 7 Hz, CH ₂ βTrp), 3.67 (3Н, s, ОCH ₃ ), 4.96 (2Н, s, СН ₂ -para-methoxybenzyl), 5.19 (1 Н, m, СН αTrp), 6.71 (4Н, s, СН ar para- methoxybenzyl), 6.89 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 6.92 (1 H, t, J ₀ = 7 Hz, H ₅ indole), 7.02 (1 H, s, H ₂ indole), 7.05 (1H, s, H ₂ Trp), 7.14 (1 H, d, J ₀ = 8 Hz, H ₄ Trp), 7.33 (3H, H ₄ indole, H ₇ Trp, H ₇ indole), 8.02 (3H, brs, NH ₂ Aib), 7.90 (1H, d, J = 8 Hz, NH amide), 10.73 (1 H, s, NH indole), 10.79 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

CН₂СН₂-индол), 29.1 (Cβ Trp), 45.5 (N-СН₂-пара-метоксибензил), 45.8 (Cα Trp), 55.5 (OCH₃), 56.8 (Cq Aib), 109.8 (C₃ Trp), 111.7 (C₇ Trp, C₇ индол), 114.0 (C₃ индол), 114.5 (C₃, C₅ пара-метоксибензил), 118.3 (C₄ индол, C₄ Trp), 118.5 (C₅ индол), 118.8 (C₅ Trp), 121.3 (C₆ индол, C₆ Trp), 127.3 (C₉ индол), 127.4 (C_g Trp), 127.6 (C₁ пара-метоксибензил), 127.9 (С₂, С₆ пара-метоксибензил, С₂ Trp, С₂ индол), 136.1 (С₈ индол), 136.4 (С₈ Trp), 154.7 (Cq триазол), 155.1 (Cq триазол), 159.2 (С₄ пара-метоксибензил), 171.9 (СО Aib).δ (ppm) 23.6 (CH ₃ Aib), 23.8 (CH ₃ Aib), 24.3 (CH ₂ CH ₂ C H ₂ -indole), 24.8 (CH ₂ C H ₂ CH ₂ -indole), 27.7 (

CH ₂ CH ₂ -indole), 29.1 (Cβ Trp), 45.5 (N- С Н ₂ -paramethoxybenzyl), 45.8 (Cα Trp), 55.5 (OCH ₃ ), 56.8 (Cq Aib), 109.8 (C ₃ Trp ), 111.7 (C ₇ Trp, C ₇ indole), 114.0 (C ₃ indole), 114.5 (C ₃ , C ₅ para-methoxybenzyl), 118.3 (C ₄ indole, C ₄ Trp), 118.5 (C ₅ indole), 118.8 (C ₅ Trp), 121.3 (C ₆ indole, C ₆ Trp), 127.3 (C ₉ indole), 127.4 (C _g Trp), 127.6 (C ₁ para-methoxybenzyl), 127.9 (C ₂ , C ₆ para- methoxybenzyl, C ₂ Trp, C ₂ indole), 136.1 (C ₈ indole), 136.4 (C ₈ Trp), 154.7 (Cq triazole), 155.1 (Cq triazole), 159.2 (C ₄ para-methoxybenzyl), 171.9 (CO Aib )

ESI-MS: measured: m / z 590.0 [M + H] ⁺ / calculated: 589.3 g / mol.

Example 15:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2-methoxy) benzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 25)

Compound 25 was obtained from BOC- (D) -Trp (10 nmol), (2-methoxyphenyl) methanamine, 3- (1H-indol-3-yl) propanhydrazide and BOC-2-amino-2-methylpropanoic acid in accordance with general synthesis scheme. The total yield after purification by HPLC was 28%.

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-СН₂-индол), 2.96 (2Н, m, СН₂-

-индол), 3.29 (2Н, m, СН₂ βTrp), 3.65 (3Н, s, ОСН₃), 5.09 (3Н, m, СН ₂-O-метоксибензил и СН αTrp), 6.49 (1 Н, d, J₀=8 Hz, Н₃ о-метоксибензил), 6.76 (1 Н, t, J₀=8 Hz, Н₅ Trp), 6.81 (1 Н, t, J₀=8 Hz, H₅ индол), 6.89 (1 H, t, J₀=7 Hz, H₆ Trp), 6.96 (1 H, t, J₀=8 Hz, H₆ индол), 6.98 (1 H, s, H₂ индол), 7.02 (3Н, m, H₄, H₅ и H₆ о- метоксибензил), 7.07 (1H, d, J₀=6 Hz, H₄ Trp), 7.18 (1 H, m, H₄ индол), 7.29 (2H, m, H₇ индол и H₇ Trp), 8.07 (3Н, brs, NH₂ Aib), 8.97 (1 H, d, J=8 Hz, NH амид), 10.80 (1 H, s, NH индол), 10.82 (1 H, s, NH индол Trp).δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.29 (3H, s, CH ₃ Aib), 2.90 (2H, m,

-CH ₂ -indole), 2.96 (2H, m, CH ₂ -

-indole), 3.29 (2Н, m, СН ₂ βTrp), 3.65 (3Н, s, ОCH ₃ ), 5.09 (3Н, m, С Н ₂ -O-methoxybenzyl and СН αTrp), 6.49 (1 Н, d, J ₀ = 8 Hz, H ₃ o-methoxybenzyl), 6.76 (1 H, t, J ₀ = 8 Hz, H ₅ Trp), 6.81 (1 H, t, J ₀ = 8 Hz, H ₅ indole), 6.89 (1 H, t, J ₀ = 7 Hz, H ₆ Trp), 6.96 (1 H, t, J ₀ = 8 Hz, H ₆ indole), 6.98 (1 H, s, H ₂ indole), 7.02 (3Н , m, H ₄ , H ₅ and H ₆ o-methoxybenzyl), 7.07 (1H, d, J ₀ = 6 Hz, H ₄ Trp), 7.18 (1 H, m, H ₄ indole), 7.29 (2H, m , H ₇ indole and H ₇ Trp), 8.07 (3H, brs, NH ₂ Aib), 8.97 (1 H, d, J = 8 Hz, NH amide), 10.80 (1 H, s, NH indole), 10.82 ( 1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-O-метоксибензил), 45.7(СН αTrp), 55.8 (ОСН₃), 56.7 (Cq Aib), 109.8 (С₃ Trp), 111.5 (С₃ о-метоксибензил), 111.8 (С₇ индол и С₇ Trp), 113.2 (С₃ индол), 118.2 (С₄ Trp), 118.4 (С₄ индол), 118.7 (С₅ индол и С₅ Trp), 121.0 (С₆ индол), 121.3 (С₆ Trp), 121.4 (С₅ о-метоксибензил), 123.0 (С₂ индол и С₂ Trp), 123.3 (С₁ о- метоксибензил), 127.0 (С₄ о-метоксибензил), 127.1 (С₉ индол), 127.3 (С₉ Trp), 129.8 (С₆ о-метоксибензил), 136.4 (С₈ индол), 136.6 (С₈ Trp), 155.2 (Cq триазол), 171.9 (СО Aib).δ (ppm) 22.8 ( C H ₂ -CH ₂ -indole), 23.6 (CH ₃ Aib), 23.7 (CH ₃ Aib), 25.8 (CH ₂ - C H ₂ -indole), 29.1 (CH ₂ βTrp), 42.3 (

-O-methoxybenzyl), 45.7 (CH αTrp), 55.8 (OCH ₃ ), 56.7 (Cq Aib), 109.8 (C ₃ Trp), 111.5 (C ₃ o-methoxybenzyl), 111.8 (C ₇ indole and C ₇ Trp) , 113.2 (C ₃ indole), 118.2 (C ₄ Trp), 118.4 (C ₄ indole), 118.7 (C ₅ indole and C ₅ Trp), 121.0 (C ₆ indole), 121.3 (C ₆ Trp), 121.4 (C ₅ o-methoxybenzyl), 123.0 _(C2 indole and _C2 Trp), 123.3 (C ₁ o- methoxybenzyl), 127.0 _(C4 o-methoxybenzyl), 127.1 _(C9 indole), 127.3 _(C9 Trp), 129.8 (C ₆ o-methoxybenzyl), 136.4 (C ₈ indole), 136.6 (C ₈ Trp), 155.2 (Cq triazole), 171.9 (CO Aib).

ESI-MS: measured: m / z 576.1 [M + H] ⁺ / calculated: 575.3 g / mol.

The following are data on other examples of compounds synthesized in accordance with general synthesis schemes (see also Table 1):

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 3):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-СН₂-индол), 2.38 (2Н, m,

-СН₂-СН₂-индол), 2.65 (4Н, m, СН₂-СН₂-

-индол и СН₂-

-фенил), 3.38 (2Н, m,

-СН₂-фенил), 3.74 (1 Н, m, СН₂ βTrp), 3.92 (1 Н, m, CH₂ βTrp), 5.23 (1 Н, m, СН αTrp), 6.78 (2Н, m, Н₅ индол и Н₅Trp), 6.93 (1Н, t, J₀=8 Hz, Н₆ Trp), 7.01 (3Н, m, Н₆ индол, Н₂ и Н₆ фенил), 7.05 (1 Н, d, J=2 Hz, Н₂ Trp), 7.08 (1 Н, d, J=2 Hz, H₂ индол), 7.15 (3Н, m, H₃, H₄ и H₅ фенил), 7.29 (1 H, d, J₀=8 Hz, H₄ Trp), 7.31 (1 H, d, J₀=8 Hz, H₇ Trp), 7.44 (1 H, d, J₀=8 Hz, H₇ индол), 7.46 (1H, d, J₀=8 Hz, H₄ индол), 8.06 (3Н, brs, NH₂ Aib), 9.05 (1 H, d, 8 Hz, NH амид), 10.76 (1H, s, NH индол), 10.85 (1 H, d, J=2 Hz, NH индол Trp).δ (ppm) 1.32 (s, 3H, CH ₃ Aib), 1.37 (s, 3H, CH ₃ Aib), 1.86 (2H, m, CH ₂ -

-CH ₂ -indole), 2.38 (2H, m,

-CH ₂ -CH ₂ -indole), 2.65 (4H, m, CH ₂ -CH ₂ -

-indole and CH ₂ -

phenyl), 3.38 (2H, m,

-CH ₂ -phenyl), 3.74 (1 Н, m, СН ₂ βTrp), 3.92 (1 Н, m, CH ₂ βTrp), 5.23 (1 Н, m, СН αTrp), 6.78 (2Н, m, Н ₅ indole and H ₅ Trp), 6.93 (1H, t, J ₀ = 8 Hz, H ₆ Trp), 7.01 (3H, m, H ₆ indole, H ₂ and H ₆ phenyl), 7.05 (1 H, d, J = 2 Hz, H ₂ Trp), 7.08 (1 H, d, J = 2 Hz, H ₂ indole), 7.15 (3H, m, H ₃ , H ₄ and H ₅ phenyl), 7.29 (1 H, d, J ₀ = 8 Hz, H ₄ Trp), 7.31 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 7.44 (1 H, d, J ₀ = 8 Hz, H ₇ indole), 7.46 (1H , d, J ₀ = 8 Hz, H ₄ indole), 8.06 (3H, brs, NH ₂ Aib), 9.05 (1 H, d, 8 Hz, NH amide), 10.76 (1H, s, NH indole), 10.85 (1 H, d, J = 2 Hz, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-индол), 27.3 (СН₂-СН₂-

-индол), 29.4 (CH₂ βTrp), 35.7 (СН₂-

-фенил), 44.5 (

-СН₂-фенил), 46.1 (CH αTrp), 56.8 (Cq Aib), 109.6 (C₃ Trp), 111.8 (C₇ индол), 111.9 (C₇ индол), 113.9 (C₃ индол), 118.3 (C₄ Trp), 118.6 (C₅ индол), 118.7 (C₄ индол), 118.9 (C₅ Trp), 121.3 (C₆ Trp), 121.4 (C₆ индол), 122.8 (C₂ индол и C₂ Trp), 127.1 (C₄ фенил), 127.3 (C₉ Trp), 127.5 (C₉ индол), 128.8 (C₂ и C₆ фенил), 129.1 (C₃ и C₅ фенил), 136.5 (С₁ фенил), 136.8 (C₈ Trp), 137.2 (C₈ индол), 154.7 (Cq триазол), 172.0 (CO Aib).δ (ppm) 23.5 (CH ₃ Aib), 23.6 ( C H ₂ -CH ₂ -CH ₂ -indole), 23.9 (CH ₃ Aib), 24.5 (CH ₂ -CH ₂ -

-indole), 27.3 (CH ₂ -CH ₂ -

-indole), 29.4 (CH ₂ βTrp), 35.7 (CH ₂ -

phenyl), 44.5 (

-CH ₂ -phenyl), 46.1 (CH αTrp), 56.8 (Cq Aib), 109.6 (C ₃ Trp), 111.8 (C ₇ indole), 111.9 (C ₇ indole), 113.9 (C ₃ indole), 118.3 (C ₄ Trp), 118.6 (C ₅ indole), 118.7 (C ₅ Indole), 118.9 (C ₅ Trp), 121.3 (C ₆ Trp), 121.4 (C ₆ indole), 122.8 (C ₂ indole and C ₂ Trp), 127.1 (C ₄ phenyl), 127.3 (C ₉ Trp), 127.5 (C ₉ indole), 128.8 (C ₂ and C ₆ phenyl), 129.1 (C ₃ and C ₅ phenyl), 136.5 (C ₁ phenyl), 136.8 ( C ₈ Trp), 137.2 (C ₈ indole), 154.7 (Cq triazole), 172.0 (CO Aib).

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-hexyl-4H-1,2,4-thiazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 16):

¹ H NMR (300 MHz, DMSO-d ⁶ , 300 K):

-CH₂-CH₂-CH₂-CH₂-CH₂), 0.95 (4H, brs, CH₃-СН₂-СН ₂-CH ₂-CH₂-CH₂), 1.06 (3H, m, CH₃-CH₂-CH₂-CH₂-CH₂-

и 1 H N-CH₂-

), 1.38 (7H, s, CH₃ Aib и 1 H N-CH₂-

), 1.97 (2H, m, СН₂-

-СН₂-индол), 2.71 (4H, m,

-СН₂-

-индол), 3.37 (2H, m, CH₂ βTrp), 3.56 (2H, m, N-

), 5.15 (1 H, m, CH αTrp), 6.91 (2H, m, H₅ индол и H₅ Trp), 7.00 (2H, m, H₆ индол и Н₆ Trp), 7.07 (2Н, s, Н₂ индол и Н₂ Trp), 7.29 (2Н, d, J₀=8 Hz, Н₇ индол и Н₇ Trp), 7.45 (2Н, d, J₀=7 Hz, Н₄ индол и Н₄ Trp), 8.15 (3Н, brs, NH₂ Aib), 9.10 (1Н, d, J=6 Hz, NH амид), 10.77 (1 H, s, NH индол), 10.85 (1 H, s, NH индол Trp).δ (ppm) 0.74 (3H, t, J = 6 Hz,

-CH ₂ -CH ₂ -CH ₂ -CH ₂ -CH _2), 0.95 (4H, brs, CH ₃ -CH ₂ -C H ₂ -C H ₂ -CH ₂ -CH _2), 1.06 (3H, m, CH ₃ —CH ₂ —CH ₂ —CH ₂ —CH ₂ -

and 1 H N-CH ₂ -

), 1.38 (7H, s, CH ₃ Aib and 1 H N-CH ₂ -

), 1.97 (2H, m, CH ₂ -

-CH ₂ -indole), 2.71 (4H, m,

-CH ₂ -

-indole), 3.37 (2H, m, CH ₂ βTrp), 3.56 (2H, m, N-

), 5.15 (1 H, m, CH αTrp), 6.91 (2H, m, H ₅ indole and H ₅ Trp), 7.00 (2H, m, H ₆ indole and H ₆ Trp), 7.07 (2H, s, N ₂ indole and H ₂ Trp), 7.29 (2H, d, J ₀ = 8 Hz, H ₇ indole and H ₇ Trp), 7.45 (2H, d, J ₀ = 7 Hz, H ₄ indole and H ₄ Trp), 8.15 (3H, brs, NH ₂ Aib), 9.10 (1H, d, J = 6 Hz, NH amide), 10.77 (1 H, s, NH indol), 10.85 (1 H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-CH₂-CH₂-CH₂-CH₂-CH₂), 22.2 (CH₃-

-CH₂-CH₂-CH₂-CH₂ и СН₂-СН₂-

-индол), 23.6 (СН₃ Aib), 23.7 (СН₃ Aib), 24.5 (

-СН₂-СН₂-индол), 25.9 (СН₃-СН₂-СН₂-

-СН₂-СН₂), 27.5 (СН₂ βTrp и СН₂-

-СН₂-индол), 29.7 (N-CH₂-

), 30.8 (СН₃-СН₂-

-СН₂-СН₂-СН₂), 43.2 (N-CH₂), 46.1 (СН αTrp), 56.8 (Cq Aib), 109.5 (С₃ Trp), 111.8 (С₇ Trp), 111.9 (С₇ индол), 113.9 (С₃ индол), 118.1 (С₄ Trp), 118.5 (С₅ индол), 118.6 (С₄ индол), 118.9 (С₅ Trp), 121.3 (С₆ индол и С₆ Trp), 122.8 (С₂ индол и С₂ Trp), 127.3 (С₉ Trp), 127.4 (С₉ индол), 136.5 (С₈ Trp), 136.8 (С₈ индол), 154.7 (Cq триазол), 172.0 (СО Aib).δ (ppm) 14.2 (

-CH ₂ -CH ₂ -CH ₂ -CH ₂ -CH ₂ ), 22.2 (CH ₃ -

—CH ₂ —CH ₂ —CH ₂ —CH _2; and CH ₂ —CH ₂ -

-indole), 23.6 (CH ₃ Aib), 23.7 (CH ₃ Aib), 24.5 (

-CH ₂ -CH ₂ -indole), 25.9 (CH ₃ -CH ₂ -CH ₂ -

-CH ₂ -CH ₂ ), 27.5 (CH ₂ βTrp and CH ₂ -

-CH ₂ -indole), 29.7 (N-CH ₂ -

), 30.8 (CH ₃ -CH ₂ -

-CH ₂ -CH ₂ -CH ₂ ), 43.2 (N-CH ₂ ), 46.1 (CH αTrp), 56.8 (Cq Aib), 109.5 (C ₃ Trp), 111.8 (C ₇ Trp), 111.9 (C ₇ indole ), 113.9 (С ₃ indole), 118.1 (С ₄ Trp), 118.5 (С ₅ indole), 118.6 (С ₄ Indole), 118.9 (С ₅ Trp), 121.3 (С ₆ indole and С ₆ Trp), 122.8 ( C ₂ indole and C ₂ Trp), 127.3 (C ₉ Trp), 127.4 (C ₉ indole), 136.5 (C ₈ Trp), 136.8 (C ₈ indole), 154.7 (Cq triazole), 172.0 (CO Aib).

(R) -N- (1- (4,5-bis (2- (1H-indol-3-yl) ethyl) -4H-1,2,4-triazol-3-yl) -2- (1H- indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 17):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-индол), 2.68 (2Н, 1, J₀=8 Hz, С-СН₂-

-индол), 2.91 (2Н, t, J₀=8 Hz, С-СН₂-СН ₂-индол), 3.34 (2Н, m, N-СН₂-СН₂-индол), 3.93 (2Н, m, СН₂ βTrp), 5.25 (1 Н, m, СН αTrp), 6.72-6.94 (4Н, m, Н₅ и Н₆ Trp, Н₅ индол из С-СН₂-СН₂-индол и Н₅ индол из N-СН₂-СН₂-индол), 6.98-7.04 (4Н, m, Н₂ Trp, Н₆ индол из С-СН₂-СН₂-индол, Н₂ и Н₆ индол из N-СН₂-СН₂-индол), 7.11 (1 Н, s, Н₂ индол из С-СН₂-СН₂-индол), 7.19 (1 Н, d, J₀=8 Hz, Н₄ индол из N-СН₂-СН₂-индол), 7.28 (3Н, m, Н₄ и Н₇ Trp, Н₇ индол из N-СН₂-СН₂-индол), 7.40 (1 Н, d, J₀=8 Hz, Н₇ индол из С-СН₂-СН₂- индол), 7.44 (1 Н, d, J₀=8 Hz, Н₄ индол из С-СН₂-СН₂-индол), 8.04 (3Н, brs, NH₂ Aib), 9.69 (1 Н, d, J=8 Hz, NН амид), 10.73(1 H, s, NH индол из С-СН₂-СН₂-индол), 10.82(1 Н, d, J=2 Hz, NH индол Trp), 10.84 (1 H, s, NH индол из N-СН₂-СН₂-индол).δ (ppm) 1.30 (3H, s, CH ₃ Aib), 1.37 (3H, s, CH ₃ Aib), 2.50 (2H, m, N-CH ₂ -

-indole), 2.68 (2H, 1, J ₀ = 8 Hz, С-СН ₂ -

-indole), 2.91 (2H, t, J ₀ = 8 Hz, С-СН ₂ -С Н ₂ -indole), 3.34 (2Н, m, N- С Н ₂ -СН ₂ -indole), 3.93 (2Н, m, CH ₂ βTrp), 5.25 (1 H, m, CH αTrp), 6.72-6.94 (4H, m, H ₅ and H ₆ Trp, H ₅ indole from C-CH ₂ -CH ₂ -indole and H ₅ indole from N-CH ₂ -CH ₂ -indole), 6.98-7.04 (4H, m, H ₂ Trp, H ₆ indole from C-CH ₂ -CH ₂ -indole, H ₂ and H ₆ indole from N-CH ₂ - CH ₂ -indole), 7.11 (1 H, s, H ₂ indole from С-СН ₂ -СН ₂ -indole), 7.19 (1 Н, d, J ₀ = 8 Hz, Н ₄ indole from N-СН ₂ - CH ₂ -indole), 7.28 (3H, m, H ₄ and H ₇ Trp, H ₇ indole from N-CH ₂ -CH ₂ -indole), 7.40 (1 H, d, J ₀ = 8 Hz, H ₇ indole from C-CH ₂ -CH ₂ - indole), 7.44 (1 H, d, J ₀ = 8 Hz, H ₄ indole from C-CH ₂ -CH ₂ -indole), 8.04 (3H, brs, NH ₂ Aib) 9.69 (1 H, d, J = 8 Hz, NH amide), 10.73 (1 H, s, NH indole from С-CH ₂ -CH ₂ -indole), 10.82 (1 Н, d, J = 2 Hz , NH indole Trp), 10.84 (1 H, s, NH indole from N-CH ₂ -CH ₂ -indole).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-индол), 23.6 (CH₃ Aib), 23.8 (CH₃ Aib), 25.4 (С-

-СН₂-индол), 26.0 (N-CH₂-

-индол), 29.6 (СН₂ βTrp), 43.9 (N-

-СН₂-индол), 46.0 (CH αTrp)), 56.8 (Cq Aib), 109.5 (C₃ индол из N-СН₂-СН₂-индол), 109.9 (С₃ Trp), 111.7 (С₇ Trp), 111.9 (С₇ индол из N-СН₂-СН₂-индол и С₇ индол из С-СН₂-СН₂-индол), 113.5 (С₃ индол из С-СН₂-СН₂-индол), 118.3 (С₄ индол из N-СН₂-СН₂-индол), 118.4 (С₄ Trp), 118.5 (С₅ индол из С-СН₂-СН₂-индол), 118.7 (С₄ индол из С-СН₂-СН₂-индол), 118.9 (С₅ Trp), 119.0 (С₅ индол из N-СН₂-СН₂-индол), 121.3 (С₆ Trp), 121.5 (С₆ индол из С-СН₂-СН₂-индол и С₆ индол из N-СН₂-СН₂-индол), 122.8 (С₂ Trp, С₂ индол из С-СН₂-СН₂-индол и индол из N-СН₂-СН₂-индол), 127.1 (С₉ Trp), 127.2 (С₉ индол из С-СН₂-СН₂-индол), 127.4 (С₉ индол из N-СН₂-СН₂-индол), 136.5 (С₈ Trp и С₈ индол из С-СН₂-СН₂-индол), 136.6 (С₈ индол из N-СН₂-СН₂-индол), 154.5 (Cq триазол), 154.8 (Cq триазол), 171.8 (СО амид).δ (ppm) 22.7 (C-CH ₂ -

-indole), 23.6 (CH ₃ Aib), 23.8 (CH ₃ Aib), 25.4 (C-

-CH ₂ -indole), 26.0 (N-CH ₂ -

-indole), 29.6 (СН ₂ βTrp), 43.9 (N-

-CH ₂ -indole), 46.0 (CH αTrp)), 56.8 (Cq Aib), 109.5 (C ₃ indole from N-СН ₂ -CH ₂ -indole), 109.9 (С ₃ Trp), 111.7 (С ₇ Trp) 111.9 (C ₇ indole from N-CH ₂ -CH ₂ -indole and C ₇ indole from C-CH ₂ -CH ₂ -indole), 113.5 (C ₃ indole from C-CH ₂ -CH ₂ -indole), 118.3 (C ₄ indole from N-CH ₂ -CH ₂ -indole), 118.4 (C ₄ Trp), 118.5 (C ₅ indole from C-CH ₂ -CH ₂ -indole), 118.7 (C ₄ indole from C-CH ₂ -CH ₂ -indole), 118.9 (C ₅ Trp), 119.0 (C ₅ indole from N-CH ₂ -CH ₂ -indole), 121.3 (C ₆ Trp), 121.5 (C ₆ indole from C-CH ₂ -CH _2- indole and C ₆ indole from N-CH ₂ -CH ₂ -indole), 122.8 (C ₂ Trp, C ₂ indole from C-CH ₂ -CH ₂ -indole and indole from N-CH ₂ -CH ₂ -indole ), 127.1 (C ₉ Trp), 127.2 (C ₉ indole from C-CH ₂ -CH ₂ -indole), 127.4 (C ₉ indole from N-CH ₂ -CH ₂ -indole), 136.5 (C ₈ Trp and C ₈ indole from C-CH ₂ -CH ₂ -indole), 136.6 (C ₈ indole from N-CH ₂ -CH ₂ -indole), 154.5 (Cq triazole), 154.8 (Cq triazole), 171.8 (CO amide).

(R) -N- (1- (4- (3-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 19):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.24 (3H, s, CH ₃ Aib), 1.27 (3H, s, CH ₃ Aib), 2.82 (4H, m, C H ₂ -C H ₂ -phenyl), 3.32 (2H, m, CH ₂ βTrp), 3.63 (3Н, s, OCH ₃ ), 5.08 (2Н, m, С Н ₂ -metho-methoxybenzyl), 5.18 (1Н, m, CH αTrp)), 6.35 (1 Н, d, J ₀ = 8 Hz, Н ₆ meta-methoxybenzyl), 6.57 (1 Н, s, Н ₂ meta-methoxybenzyl), 6.82 (1 Н, t, J ₀ = 8 Hz, Н ₅ Trp), 6.84 (1 Н, d, J ₀ = 8 Hz, H ₄ meta-methoxybenzyl), 6.99 (1 H, t, J ₀ = 8 Hz, H ₆ Trp), 7.08 (1H, m, H ₄ phenyl), 7.11-7.16 (5H, m, H ₂ and H ₄ Trp, H ₂ and H ₆ phenyl, H ₅ meta-methoxybenzyl), 7.20 (2H, m, H ₃ and H ₅ phenyl), 7.27 (1H, d, J ₀ = 8 Hz, H ₇ Trp) 8.01 (3H, brs, NH ₂ Aib), 8.96 (1 H, d, J = 8 Hz, NH amide), 10.81 (1 H, d, J = 2 Hz, NH indole).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.4 (C H ₂ -CH ₂ phenyl), 29.1 (CH ₂ βTrp), 32.7 (CH ₂ - C H ₂ phenyl), 45.7 (CH αTrp), 45.8 (CH ₂ -metha-methoxybenzyl), 55.5 (OCH ₃ ), 56.7 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 112.5 (C ₂ meta-methoxybenzyl), 113.5 (C ₄ meta-methoxybenzyl), 118.2 (C ₄ Trp), 118.4 (C ₆ meta-methoxybenzyl), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.8 (C ₂ Trp), 126.5 (C ₄ phenyl), 127.3 (C ₉ Trp), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 130.5 (C ₅ meta-methoxybenzyl), 136.4 (C ₈ Trp), 137.7 (C ₁ meta-methoxybenzyl) 170.9 (C ₁ phenyl), 154.6 (Cq triazole), 154.9 (Cq triazole), 160.1 (C ₃ meta-methoxybenzyl), 171.9 (CO amide).

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 20):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-фенил), 2.82 (2Н, m, СН₂-

-фенил), 3.35 (2Н, d, J=7 Hz, СН₂ βTrp), 3.68 (3Н, s, ОСН₃), 5.02 (2Н, s, СН₂-пара-метоксибензил), 5.22 (1 Н, m, СН αTrp), 6.73-6.81 (4Н, m, СНаr пара-метоксибензил), 6.84 (1 Н, t, J₀=7 Hz, Н₅ Trp), 7.00 (1 Н, t, J₀=7 Hz, H₆ Trp), 7.05-7.11 (4H, m, H₂ и H₆ фенил, H₂ и H₄ Trp), 7.14-7.22 (3H, m, H₃, H₄ и H₅ фенил), 7.29 (1 H, d, J₀=8 Hz, H₇ Trp), 8.09 (3H, brs, NH₂ Aib), 8.99 (1 H, d, J=8 Hz, NH амид), 10.83 (1 H, s, NH индол Trp).δ (ppm) 1.28 (3H, s, CH ₃ Aib), 1.32 (3H, s, CH ₃ Aib), 2.46 (2H, m, CH ₂ -

phenyl), 2.82 (2H, m, CH ₂ -

phenyl), 3.35 (2H, d, J = 7 Hz, CH ₂ βTrp), 3.68 (3H, s, OCH ₃ ), 5.02 (2H, s, CH ₂ -paramethoxybenzyl), 5.22 (1 H, m , СН αTrp), 6.73-6.81 (4Н, m, СНа para-methoxybenzyl), 6.84 (1 Н, t, J ₀ = 7 Hz, Н ₅ Trp), 7.00 (1 Н, t, J ₀ = 7 Hz, H ₆ Trp), 7.05-7.11 (4H, m, H ₂ and H ₆ phenyl, H ₂ and H ₄ Trp), 7.14-7.22 (3H, m, H ₃ , H ₄ and H ₅ phenyl), 7.29 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 8.09 (3H, brs, NH ₂ Aib), 8.99 (1 H, d, J = 8 Hz, NH amide), 10.83 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 29.1 (CH₂ βTrp), 32.6 (СН₂-

-фенил), 45.5 (

-пара-метоксибензил), 45.7 (CH αTrp), 55.5 (OCH₃), 56.8 (Cq Aib), 109.7 (C₃ Trp), 111.8 (C₇ Trp), 114.6 (C₃ и C₅ пара-метоксибензил), 118.3 (С₄ Trp), 118.7 (С₅ Trp), 121.3 (С₆ Trp), 124.9 (С₂ Trp), 126.6 (С₂ и С₆ фенил), 127.3 (C₉ Trp), 127.6 (С₁ пара-метоксибензил), 128.0 (С₂ и С₆ пара-метоксибензил), 128.7 (С₃, С₄ и С₅ фенил), 136.4 (С₈ Trp), 140.8 (С₁ фенил), 154.5 (Cq триазол), 154.8 (Cq триазол), 159.2 (С₄ пара-метоксибензил), 172.0 (СО Aib).δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.5 (

-CH ₂ -phenyl), 29.1 (CH ₂ βTrp), 32.6 (CH ₂ -

phenyl), 45.5 (

-para-methoxybenzyl), 45.7 (CH αTrp), 55.5 (OCH ₃ ), 56.8 (Cq Aib), 109.7 (C ₃ Trp), 111.8 (C ₇ Trp), 114.6 (C ₃ and C ₅ para-methoxybenzyl), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.9 (C ₂ Trp), 126.6 (C ₂ and C ₆ phenyl), 127.3 (C ₉ Trp), 127.6 (C ₁ pair -methoxybenzyl), 128.0 (C ₂ and C ₆ para-methoxybenzyl), 128.7 (C ₃ , C ₄ and C ₅ phenyl), 136.4 (C ₈ Trp), 140.8 (C ₁ phenyl), 154.5 (Cq triazole), 154.8 (Cq triazole), 159.2 (C ₄ para-methoxybenzyl), 172.0 (CO Aib).

(R) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-2-methylpropanamide (Compound 22):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 2.47 (2Н, m,

-СН₂-СН₂-фенил), 2.52 (2Н, t, ³J=7 Hz, СН₂-СН₂-

-фенил), 3.35 (2Н, d, J=7 Hz, CH₂ βTrp), 3.68 (3Н, s, ОСН₃), 4.98 (2Н, s, СН₂-пара-метоксибензил), 5.20 (1 Н, m, СН αTrp), 6.75 (4Н, m, СНаr пара-метоксибензил), 6.82 (1 Н, 1, J₀=7 Hz, Н₅ Trp), 6.99 (1 Н, t, J₀=7 Hz, H₆ Trp), 7.04-7.07 (4H, m, H₂ и Н₆ фенил, Н₂ и Н₄ Trp), 7.13-7.24 (3Н, m, Н₃, Н₄ и Н₅ фенил), 7.29 (1Н, d, J₀=8 Hz, Н₇ Trp), 8.03 (3Н, brs, NH₂ Aib), 8.96 (1 H, d, J=8 Hz, NH амид), 10.80 (1 H, d, J=2 Hz, NH индол Trp).δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.31 (3H, s, CH ₃ Aib), 1.73 (2H, m, CH ₂ -

-CH ₂ -phenyl), 2.47 (2H, m,

-CH ₂ -CH ₂ phenyl), 2.52 (2H, t, ³ J = 7 Hz, CH ₂ -CH ₂ -

phenyl), 3.35 (2H, d, J = 7 Hz, CH ₂ βTrp), 3.68 (3H, s, OCH ₃ ), 4.98 (2H, s, CH ₂ -paramethoxybenzyl), 5.20 (1 N, m , СН αTrp), 6.75 (4Н, m, СНа para-methoxybenzyl), 6.82 (1 Н, 1, J ₀ = 7 Hz, Н ₅ Trp), 6.99 (1 Н, t, J ₀ = 7 Hz, H ₆ Trp), 7.04-7.07 (4H, m, H ₂ and H ₆ phenyl, H ₂ and H ₄ Trp), 7.13-7.24 (3H, m, H ₃ , H ₄ and H ₅ phenyl), 7.29 (1H, d , J ₀ = 8 Hz, H ₇ Trp), 8.03 (3H, brs, NH ₂ Aib), 8.96 (1 H, d, J = 8 Hz, NH amide), 10.80 (1 H, d, J = 2 Hz , NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 28.5 (

-СН₂-СН₂-фенил), 29.2 (CH₂ βTrp), 34.7 (СН₂-СН₂-

-фенил), 45.5 (

-пара-метоксибензил), 45.8 (СН αTrp), 55.5 (ОСН₃), 56.8 (Cq Aib), 109.8 (С₃ Trp), 111.8 (С₇ Trp), 114.6 (С₃ и С₅ пара-метоксибензил), 118.3 (С₄ Trp), 118.7 (С₅ Trp), 121.3 (С₆ Trp), 124.9 (С₂ Trp), 126.2 (С₂ и С₆ фенил), 127.3 (С₉ Trp), 127.8 (C₁ пара-метоксибензил), 127.9 (С₂ и С₆ пара-метоксибензил), 128.7 (С₃, С₄ и С₅ фенил), 136.4 (С₈ Trp), 141.7 (С₁ фенил), 154.8 (Cq триазол), 159.2 (С₄ пара-метоксибензил), 171.9 (СО Aib).δ (ppm) 23.6 (CH ₃ Aib), 23.6 (CH ₃ Aib), 24.06 (CH ₂ -

-CH ₂ -phenyl), 28.5 (

-CH ₂ -CH ₂ -phenyl), 29.2 (CH ₂ βTrp), 34.7 (CH ₂ -CH ₂ -

phenyl), 45.5 (

-para-methoxybenzyl), 45.8 (CH αTrp), 55.5 (OCH ₃ ), 56.8 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 114.6 (C ₃ and C ₅ para-methoxybenzyl), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.9 (C ₂ Trp), 126.2 (C ₂ and C ₆ phenyl), 127.3 (C ₉ Trp), 127.8 (C ₁ pair -methoxybenzyl), 127.9 (C ₂ and C ₆ para-methoxybenzyl), 128.7 (C ₃ , C ₄ and C ₅ phenyl), 136.4 (C ₈ Trp), 141.7 (C ₁ phenyl), 154.8 (Cq triazole), 159.2 (C ₄ para-methoxybenzyl), 171.9 (CO Aib).

(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5- (3- (1H-indol-3-yl) propyl) -4H-1,2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 24):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-СН₂-индол), 2.34 (2Н, m,

-СН₂-СН₂-индол), 2.48 (2Н, m, N-СН₂-

-индол), 2.80 (2Н, m, СН₂-СН₂-

-индол), 3.34 (2Н, m, N-СН ₂-СН₂-индол), 3.94 (2Н, m, СН₂ βTrp), 5.27 (1 Н, m, CH αTrp), 6.73-6.94 (4Н, m, Н₅ и Н₆ Trp, Н₅ индол из N-СН₂-СН₂-индол и Н₅ индол из СН₂-СН₂-СН₂-индол), 6.99-7.04 (5Н, m, Н₂ Trp, Н₂ и Н₆ индол из N-СН₂-СН₂-индол, Н₂ и Н₆ индол из СН₂-СН₂-СН₂-индол), 7.20 (1Н, d, J₀=8 Hz, Н₄ индол из N-СН₂-СН₂-индол), 7.29 (3Н, m, Н₄ и Н₇ Trp, Н₇ индол из N-СН₂-СН₂-индол), 7.40 (1Н, d, J₀=8 Hz, Н₇ индол из СН₂-СН₂-СН₂-индол), 7.44 (1 Н, d, J₀=8 Hz, Н₄ индол из СН₂-СН₂-СН₂-индол), 8.05 (3Н, brs, NH₂ Aib), 9.07 (1 Н, d, J=8 Hz, NH амид), 10.75 (1 H, s, NH индол из СН₂-СН₂-СН₂-индол), 10.86 (1 H, s, NH индол Trp), 10.90 (1 H, s, NH индол из N-СН₂-СН₂-индол).δ (ppm) 1.29 (3H, s, CH ₃ Aib), 1.35 (3H, s, CH ₃ Aib), 1.78 (2H, m, CH ₂ -

-CH ₂ -indole), 2.34 (2H, m,

-CH ₂ -CH ₂ -indole), 2.48 (2H, m, N-CH ₂ -

-indole), 2.80 (2H, m, CH ₂ -CH ₂ -

-indole), 3.34 (2Н, m, N- СH ₂ -CH ₂ -indole), 3.94 (2Н, m, СН ₂ βTrp), 5.27 (1 Н, m, CH αTrp), 6.73-6.94 (4Н, m, H ₅ and H ₆ Trp, H ₅ indole from N-CH ₂ -CH ₂ -indole and H ₅ indole from CH ₂ -CH ₂ -CH ₂ -indole), 6.99-7.04 (5H, m, H ₂ Trp , H ₂ and H ₆ indole from N-CH ₂ -CH ₂ -indole, H ₂ and H ₆ indole from CH ₂ -CH ₂ -CH ₂ -indole), 7.20 (1H, d, J ₀ = 8 Hz, N ₄ indole from N-CH ₂ -CH ₂ -indole), 7.29 (3H, m, H ₄ and H ₇ Trp, H ₇ indole from N-CH ₂ -CH ₂ -indole), 7.40 (1H, d, J ₀ = 8 Hz, H ₇ indole from CH ₂ -CH ₂ -CH ₂ -indole), 7.44 (1 N, d, J ₀ = 8 Hz, H ₄ indole from CH ₂ -CH ₂ -CH ₂ -indole), 8.05 (3H, brs, NH ₂ Aib), 9.07 (1 H, d, J = 8 Hz, NH amide), 10.75 (1 H, s, NH indole from CH ₂ -CH ₂ -CH ₂ -indole), 10.86 ( 1 H, s, NH indole Trp), 10.90 (1 H, s, NH indole from N-CH ₂ -CH ₂ -indole).

¹³ With NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-СН₂-индол), 25.8 (СН₂-СН₂-

-индол), 27.2 (СН₂-

-СН₂-индол), 29.4 (СН₂ βTrр), 44.1 (N-СН₂-СН₂-индол), 46.0 (СН αTrp), 52.9 (N-СН₂-СН₂-индол), 56.8 (Cq Aib), 109.7 (С₃ Trp и С₃ индол из N-СН₂-СН₂-индол), 111.8 (С₇ Trp), 111.9 (С₇ индол из N-СН₂-СН₂-индол и С₇ индол из СН₂-СН₂-СН₂-индол), 114.0 (С₃ индол из СН₂-СН₂-СН₂-индол), 118.2 (С₄ индол из N-СН₂-СН₂-индол), 118.3 (С₄ Trp), 118.5 (С₅ индол из СН₂-СН₂-СН₂-индол), 118.6 (С₄ индол из СН₂-СН₂-СН₂-индол), 118.9 (С₅ Trp), 119.0 (С₅ индол из N-СН₂-СН₂-индол), 121.3 (С₆ Trp), 121.4 (С₆ индол из СН₂-СН₂-СН₂- индол), 121.6 (С₆ индол из N-СН₂-СН₂-индол), 122.7 (С₂ Trp, С₂ индол из N-СН₂-СН₂-индол и С₂ индол из СН₂-СН₂-СН₂-индол), 127.1 (С₉ Trp), 127.4 (С₉ индол из N-СН₂-СН₂-индол и С₉ индол из СН₂-СН₂-СН₂-индол), 136.4 (С₈ Trp), 136.5 (С₈ индол из СН₂-СН₂-СН₂-индол), 136.7 (С₈ индол из N-СН₂-СН₂-индол), 154.7 (2 Cq триазол), 171.9 (СО амид).δ (ppm) 23.6 (CH ₃ Aib), 23.8 (CH ₃ Aib), 24.5 (

-CH ₂ -CH ₂ -indole), 25.8 (CH ₂ -CH ₂ -

-indole), 27.2 (CH ₂ -

-CH ₂ -indole), 29.4 (CH ₂ βTrp), 44.1 (N-CH ₂ - С Н ₂ -indole), 46.0 (СН αTrp), 52.9 (N- С Н ₂ -CH ₂ -indole), 56.8 ( Cq Aib), 109.7 (C ₃ Trp and C ₃ indole from N-CH ₂ -CH ₂ -indole), 111.8 (C ₇ Trp), 111.9 (C ₇ indole from N-CH ₂ -CH ₂ -indole and C ₇ indole from CH ₂ -CH ₂ -CH ₂ -indole), 114.0 (C ₃ indole from CH ₂ -CH ₂ -CH ₂ -indole), 118.2 (C ₄ indole from N-CH ₂ -CH ₂ -indole), 118.3 (C ₄ Trp), 118.5 (C ₅ indole from CH ₂ -CH ₂ -CH ₂ -indole), 118.6 (C ₄ indole from CH ₂ -CH ₂ -CH ₂ -indole), 118.9 (C ₅ Trp), 119.0 (C ₅ indole from N-CH ₂ -CH ₂ -indole), 121.3 (C ₆ Trp), 121.4 (C ₆ indole from CH ₂ -CH ₂ -CH ₂ -indole), 121.6 (C ₆ indole from N-CH ₂ -CH ₂ -indole), 122.7 (C ₂ Trp, C ₂ indole from N-CH ₂ -CH ₂ -indole and C ₂ indole from CH ₂ -CH ₂ -CH ₂ -indole), 127.1 (C ₉ Trp) , 127.4 (C ₉ indole from N-CH ₂ -CH ₂ -indole and C ₉ indole from CH ₂ -CH ₂ -CH ₂ -indole), 136.4 (C ₈ Trp), 136.5 (C ₈ indole from CH ₂ -CH ₂ -CH ₂ -indole), 136.7 (C ₈ indole from N-CH ₂ -CH ₂ -indole), 154.7 (2 Cq triazole), 171.9 (СО amide).

(R) -N- (1- (4- (2-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 26):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.29 (2Н, m, CH₂ βTrp), 3.65 (3Н, s, ОСН₃), 4.97-5.21 (3Н, m, СН αTrp и СН₂-о-метоксибензил), 6.52 (1 Н, d, J₀=7 Hz, Н₃ о-метоксибензил), 6.78 (1 Н, t, J₀=7 Hz, Н₅ Trp), 6.82 (1 Н, t, J₀=8 Hz, H₆ Trp), 6.84-7.04 (3H, m, H₄, H₅ и H₆ о-метоксибензил), 7.15 (1 H, d, J₀=7 Hz, H₄ Trp), 7.19-7.29 (4H, m, H₃, H₄ и H₅ фенил, H₇ Trp), 8.03 (3H, brs, NH₂ Aib), 8.94 (1 H, d, J=8 Hz, NH амид), 10.82 (1 H, s, NH индол Trp).δ (ppm) 1.26 (3H, s, CH ₃ Aib), 1.29 (3H, s, CH ₃ Aib), 2.78-2.92 (4H, m,

-

phenyl), 3.29 (2H, m, CH ₂ βTrp), 3.65 (3H, s, OCH ₃ ), 4.97-5.21 (3H, m, CH αTrp and CH ₂ -omethoxybenzyl), 6.52 (1 H, d , J ₀ = 7 Hz, H ₃ o-methoxybenzyl), 6.78 (1 N, t, J ₀ = 7 Hz, H ₅ Trp), 6.82 (1 N, t, J ₀ = 8 Hz, H ₆ Trp), 6.84-7.04 (3H, m, H ₄ , H ₅ and H ₆ o-methoxybenzyl), 7.15 (1 H, d, J ₀ = 7 Hz, H ₄ Trp), 7.19-7.29 (4H, m, H ₃ , H ₄ and H ₅ phenyl, H ₇ Trp), 8.03 (3H, brs, NH ₂ Aib), 8.94 (1 H, d, J = 8 Hz, NH amide), 10.82 (1 H, s, NH indole Trp) .

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 29.0 (CH₂ βTrp), 32.5 (СН₂-

-фенил), 42.3 (СН₂-O-метоксибензил), 45.7 (СН αTrp), 55.8 (ОСН₃), 56.7 (Cq Aib), 109.7 (C₃ Trp), 111.5 (C₇ Trp), 111.8 (C₃ о-метоксибензил), 118.2 (C₄ Trp), 118.7 (C₅ Trp), 121.0 (C₆ Trp), 121.3 (C₅ о-метоксибензил), 123.2 (С₁ о-метоксибензил), 124.9 (С₂ Trp), 126.6 (С₂ и С₆ фенил), 127.2 (С₉ Trp и С₄ о-метоксибензил), 128.7 (С₃, С₄ и С₅ фенил), 129.9 (С₆ о-метоксибензил), 136.4 (С₈ Trp), 140.6 (С₁ фенил), 154.8 (Cq триазол), 155.2 (Cq триазол), 156.7 (С₂ О-метоксибензил), 171.9 (СО Aib).δ (ppm) 23.6 (CH ₃ Aib), 23.7 (CH ₃ Aib), 26.3 (

-CH ₂ -phenyl), 29.0 (CH ₂ βTrp), 32.5 (CH ₂ -

phenyl), 42.3 (CH ₂ -O-methoxybenzyl), 45.7 (CH αTrp), 55.8 (OCH ₃ ), 56.7 (Cq Aib), 109.7 (C ₃ Trp), 111.5 (C ₇ Trp), 111.8 (C ₃ o-methoxybenzyl), 118.2 (C ₄ Trp), 118.7 (C ₅ Trp), 121.0 (C ₆ Trp), 121.3 (C ₅ o-methoxybenzyl), 123.2 (C ₁ o-methoxybenzyl), 124.9 (C ₂ Trp) 126.6 (C ₂ and C ₆ phenyl), 127.2 (C ₉ Trp and C ₄ o-methoxybenzyl), 128.7 (C ₃ , C ₄ and C ₅ phenyl), 129.9 (C ₆ o-methoxybenzyl), 136.4 (C ₈ Trp), 140.6 (C ₁ phenyl), 154.8 (Cq triazole), 155.2 (Cq triazole), 156.7 (C ₂ O-methoxybenzyl), 171.9 (CO Aib).

(R) -N- (2- (1H-indol-3-yl) -1- (4- (naphthalen-1-ylmethyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 27):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 2.88 (2Н, m, СН₂-

-фенил), 3.26 (2Н, dd, ³J=14 Hz и 6 Hz, СН₂ βTrp), 3.36 (2Н, dd, ³J=14 Hz и 9 Hz, CH₂ βTrp), 4.99 (1 H, m, СН αTrp), 5.65 (1 H, d, ³J=18 Hz, СН ₂-нафтил), 5.78 (1 H, d, ³J=18 Hz,

-нафтил), 6.29 (1 H, d, J₀=7 Hz, H₂ нафтил), 6.45 (1 H, t, J₀=7 Hz, H₅ Trp), 6.62 (1 H, d, J₀=8 Hz, H₄ Trp), 6.88 (1 H, 1, J₀=8 Hz, H₆ Trp), 7.04-7.06 (4H, m, H₂ и H₇ Trp, H₂ и H₆ фенил), 7.07-7.25 (H₃ нафтил, H₃, H₄ и H₅ фенил), 7.57-7.60 (2H, m, H₆ и H₇ нафтил), 7.86 (1 H, d, J₀=8 Hz, H₄ нафтил), 7.98-8.00 (4H, m, H₅ и H₈ нафтил, NH₂ Aib), 8.96 (1 H, d, J=8 Hz, NH амид), 10.77 (1 H, s, NH индол Trp).δ (ppm) 1.21 (3H, s, CH ₃ Aib), 1.25 (3H, s, CH ₃ Aib), 2.46 (2H, m,

-CH ₂ -phenyl), 2.88 (2H, m, CH ₂ -

phenyl), 3.26 (2Н, dd, ³ J = 14 Hz and 6 Hz, СН ₂ βTrp), 3.36 (2Н, dd, ³ J = 14 Hz and 9 Hz, CH ₂ βTrp), 4.99 (1 H, m , СН αTrp), 5.65 (1 H, d, ³ J = 18 Hz, С Н _2- naphthyl), 5.78 (1 H, d, ³ J = 18 Hz,

naphthyl), 6.29 (1 H, d, J ₀ = 7 Hz, H ₂ naphthyl), 6.45 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 6.62 (1 H, d, J ₀ = 8 Hz, H ₄ Trp), 6.88 (1 H, 1, J ₀ = 8 Hz, H ₆ Trp), 7.04-7.06 (4H, m, H ₂ and H ₇ Trp, H ₂ and H ₆ phenyl), 7.07 -7.25 (H ₃ naphthyl, H ₃ , H ₄ and H ₅ phenyl), 7.57-7.60 (2H, m, H ₆ and H ₇ naphthyl), 7.86 (1 H, d, J ₀ = 8 Hz, H ₄ naphthyl ), 7.98-8.00 (4H, m, H ₅ and H ₈ naphthyl, NH ₂ Aib), 8.96 (1 H, d, J = 8 Hz, NH amide), 10.77 (1 H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

СН₂-фенил), 29.2 (CH₂ βTrp), 32.6 (СН₂-

-фенил), 43.8 (

-нафтил), 45.6 (СН αTrp), 56.7 (Cq Aib), 109.7 (C₃Trp), 111.7 (C₇ Trp), 117.9 (C₄ Trp), 118.4 (C₅ Trp), 121.1 (C₆ Trp), 122.1 (C₂ нафтил), 123.0 (C₈ нафтил), 124.9 (C₂ Trp), 125.9 (C₃ нафтил), 126.5 (C₆ нафтил), 126.9 (C₂ и C₆ фенил), 127.0 (C₉ Trp и C₇ нафтил), 127.1 (C₄ нафтил), 128.4 (C₅ нафтил), 128.7 (C₃, C₄ и C₅ фенил), 130.0 (C₉ нафтил), 131.7 (С₁ нафтил), 133.6 (C₁₀ нафтил), 136.4 (C₈ Trp), 140.8 (C_t фенил), 154.8 (Cq триазол), 155.3 (Cq триазол), 171.9 (СО Aib).δ (ppm) 23.5 (CH ₃ Aib), 23.6 (CH ₃ Aib), 26.3 (

CH ₂ -phenyl), 29.2 (CH ₂ βTrp), 32.6 (CH ₂ -

phenyl), 43.8 (

naphthyl), 45.6 (CH αTrp), 56.7 (Cq Aib), 109.7 (C ₃ Trp), 111.7 (C ₇ Trp), 117.9 (C ₄ Trp), 118.4 (C ₅ Trp), 121.1 (C ₆ Trp) , 122.1 (C ₂ naphthyl), 123.0 (C ₈ naphthyl), 124.9 (C ₂ naphthyl), 125.9 (C ₃ naphthyl), 126.5 (C ₆ naphthyl), 126.9 (C ₂ and C ₆ phenyl), 127.0 (C ₉ Trp and C ₇ naphthyl), 127.1 (C ₄ naphthyl), 128.4 (C ₅ naphthyl), 128.7 (C ₃ , C ₄ and C ₅ phenyl), 130.0 (C ₉ naphthyl), 131.7 (C ₁ naphthyl), 133.6 ( C ₁₀ naphthyl), 136.4 (C ₈ Trp), 140.8 (C _t phenyl), 154.8 (Cq triazole), 155.3 (Cq triazole), 171.9 (CO Aib).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3,4-dichlorobenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 28):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-СН₂-индол), 2.96 (2Н, m, СН₂-

-индол), 3.32 (2Н, m, СН₂ βTrp), 5.13 (3Н, m, CH αTrp) и СН₂-мета,пара-дихлоробензил), 6.58 (1 Н, d, J₀=8 Hz, Н₆ мета,пара-дихлоробензил), 6.85 (1Н, t, J₀=7 Hz, Н₅ Trp), 6.96 (1 Н, t, J₀=7 Hz, H₅ индол), 7.01 (2H, m, H₆ индол и H₆ Trp), 7.04 (1 H, s, H₂ Trp), 7.08 (1 H, s, H₂ индол), 7.13 (1 Н, d, J₀=8 Hz, H₅ мета,пара-дихлоробензил), 7.20-7.30 (4Н, m, Н₄ и Н₇ индол, Н₇ Trp и Н₂ мета,пара-дихлоробензил), 7.36 (1 Н, d, J₀=8 Hz, Н₄ Trp), 8.08 (3Н, brs, NH₂ Aib), 8.98 (1 H, d, J=8 Hz, NH амид), 10.80 (1 H, s, NH индол), 10.82 (1 H, S, NH индол Trp).δ (ppm) 1.26 (6H, s, CH ₃ Aib), 2.87 (2H, m,

-CH ₂ -indole), 2.96 (2H, m, CH ₂ -

-indole), 3.32 (2Н, m, СН ₂ βTrp), 5.13 (3Н, m, CH αTrp) and СН ₂ -meta, para-dichlorobenzyl), 6.58 (1 Н, d, J ₀ = 8 Hz, Н ₆ meta, para-dichlorobenzyl), 6.85 (1Н, t, J ₀ = 7 Hz, Н ₅ Trp), 6.96 (1 Н, t, J ₀ = 7 Hz, H ₅ indole), 7.01 (2H, m, H ₆ indole and H ₆ Trp), 7.04 (1 H, s, H ₂ indp), 7.08 (1 H, s, H ₂ indole), 7.13 (1 H, d, J ₀ = 8 Hz, H ₅ meta, para dichlorobenzyl), 7.20-7.30 (4Н, m, Н ₄ and Н ₇ indole, Н ₇ Trp and Н ₂ meta, para-dichlorobenzyl), 7.36 (1 Н, d, J ₀ = 8 Hz, Н ₄ Trp), 8.08 (3H, brs, NH ₂ Aib), 8.98 (1 H, d, J = 8 Hz, NH amide), 10.80 (1 H, s, NH indole), 10.82 (1 H, S, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-индол), 23.4 (CH₃ Aib), 23.8 (CH₃ Aib), 25.8 (

-СН₂-индол), 29.0 (CH₂ βTrp), 44.8 (СН₂-мета,пара-дихлоробензил), 45.6 (CH αTrp), 56.8 (Cq Aib), 109.7 (C₃ индол), 111.8 (C₇ индол и C₇ Trp), 118.1 (C₄ Trp), 118.4 (C₅ индол), 118.6 (C₄ индол и C₅ Trp), 121.3 (C₆ индол и C₆ Trp), 123.0 (C₂ индол и C₂ Trp), 126.4 (C₆ мета,пара-дихлоробензил), 127.1 (C₉ Trp), 127.3 (C₉ индол), 128.6 (C₂ мета,пара-дихлоробензил), 130.9 (C₄ мета,пара-дихлоробензил), 131.3 (C₅ мета,пара-дихлоробензил), 132.0 (C₃ мета,пара-дихлоробензил), 136.4 (C₈ Trp), 136.6 (C₈ индол), 137.2 (С₁ мета,пара-дихлоробензил), 154.7 (Cq триазол), 155.1 (Cq триазол), 172.0 (CO Aib)δ (ppm) 22.8 (CH ₂ -

-indole), 23.4 (CH ₃ Aib), 23.8 (CH ₃ Aib), 25.8 (

-CH ₂ -indole), 29.0 (CH ₂ βTrp), 44.8 (CH ₂ -metha, para-dichlorobenzyl), 45.6 (CH αTrp), 56.8 (Cq Aib), 109.7 (C ₃ indole), 111.8 (C ₇ indole and C ₇ Trp), 118.1 (C ₄ Trp), 118.4 (C ₅ indole), 118.6 (C ₄ indole and C ₅ Trp), 121.3 (C ₆ indole and C ₆ Trp), 123.0 (C ₂ indole and C ₂ Trp), 126.4 (C ₆ meta, para-dichlorobenzyl), 127.1 (C ₉ Trp), 127.3 (C ₉ indole), 128.6 (C ₂ meta, para-dichlorobenzyl), 130.9 (C ₄ meta, para-dichlorobenzyl), 131.3 (C ₅ meta, para-dichlorobenzyl), 132.0 (C ₃ meta, para-dichlorobenzyl), 136.4 (C ₈ Trp), 136.6 (C ₈ indole), 137.2 (C ₁ meta, para-dichlorobenzyl), 154.7 (Cq triazole), 155.1 (Cq triazole), 172.0 (CO Aib)

(R) -N- (1- (4- (4-fluorobenzyl) -5-benzyl-4AV-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 30):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.29 (3H, s, CH ₃ Aib), 3.33 (2H, m, CH ₂ βTrp), 4.02 (2H, s, CH ₂ -benzyl), 5.10 (3H, m, CH ₂ -parafluorobenzyl and CH αTrp), 6.71 (2H, m, H ₃ and H ₅ para-fluorobenzyl), 6.80 (1 H, t, J ₀ = 8 Hz, H ₅ Trp), 6.90 (2H, d, J ₀ = 8 Hz, H ₂ and H ₆ para-fluorobenzyl), 6.94 (1 H, 1, J ₀ = 8 Hz, H ₆ Trp), 6.99-7.10 (4H, m, H ₂ and H ₄ Trp, H ₂ and H ₆ benzyl), 7.20 (3H, m, H ₃ , H ₄ and H ₅ benzyl), 7.27 (1H, d, J ₀ = 8 Hz, H ₇ Trp), 8.09 (3H , brs, NH ₂ Aib), 8.97 (1 H, d, J = 8 Hz, NH amide), 10.79 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 29.0 (CH ₂ βTrp), 31.1 (CH ₂ -benzyl), 45.7 (CH ₂ -parafluorobenzyl), 45.8 (CH αTrp), 56.8 (Cq Aib), 109.6 (C ₃ Trp), 111.8 (C ₇ Trp), 115.6 and 115.9 (C ₃ and C ₅ para-fluorobenzyl), 118.2 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.8 (C ₂ Trp), 127.1 (C ₄ benzyl), 127.2 (C ₉ Trp), 128.8 and 128.9 (C ₂ and C ₆ para-fluorobenzyl), 129.4 (C ₂ , C ₃ , C ₅ and C ₆ para-fluorobenzyl), 131.6 (C ₁ para-fluorobenzyl), 135.9 (C ₁ benzyl), 136.4 (C ₈ Trp), 154.0 (C ₄ para-fluorobenzyl), 155.3 (Cq triazole), 172.0 (CO amide) .

(R) -N- (1- (4- (4-methylbenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-amino-2-methylpropanamide (Compound 33):

^1H NMR (300 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 2.23 (3Н, s, СН₃ пара-метилбензил), 2.49-2.54 (4Н, m,

-СН₂-

-фенил), 3.33 (2Н, m, СН₂ βTrp), 5.04 (2Н, s, СН₂-пара-метилбензил), 5.16 (1 H, m, CH αTrp)), 6.74 (2H, d, J₀=8 Hz, H₃ и H₅ пара-метилбензил), 6.80 (1 H, t, J₀=7 Hz, H₅ Trp), 6.98 (1 H, t, J₀=7 Hz, H₆ Trp), 7.03 (1 H, d, J=2 Hz, H₂ Trp), 7.06 (5H, m, CHar фенил), 7.14 (1 H, d, J₀=7 Hz, H₄ Trp), 7.20 (2H, d, J₀=7 Hz, H₂ и H₆ пара-метилбензил), 7.27 (1 H, d, J₀=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib), 8.95 (1 H, d, J=8 Hz, NH амид), 10.80 (1 H, d, J=2 Hz, NH индол Trp).δ (ppm) 1.25 (3H, s, CH ₃ Aib), 1.28 (3H, s, CH ₃ Aib), 1.73 (2H, m, CH ₂ -

-CH ₂ -phenyl), 2.23 (3H, s, CH ₃ para-methylbenzyl), 2.49-2.54 (4H, m,

-CH ₂ -

phenyl), 3.33 (2H, m, CH ₂ βTrp), 5.04 (2H, s, CH ₂ para-methylbenzyl), 5.16 (1 H, m, CH αTrp)), 6.74 (2H, d, J ₀ = 8 Hz, H ₃ and H ₅ para-methylbenzyl), 6.80 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 6.98 (1 H, t, J ₀ = 7 Hz, H ₆ Trp), 7.03 (1 H, d, J = 2 Hz, H ₂ Trp), 7.06 (5H, m, CHar phenyl), 7.14 (1 H, d, J ₀ = 7 Hz, H ₄ Trp), 7.20 (2H, d, J ₀ = 7 Hz, H ₂ and H ₆ para-methylbenzyl), 7.27 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 8.01 (3H, brs, NH ₂ Aib), 8.95 (1 H, d, J = 8 Hz, NH amide), 10.80 (1 H, d, J = 2 Hz, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 28.5 (

-СН₂-СН₂-фенил), 29.1 (CH₂ βTrp), 34.7 (СН₂-СН₂-

-фенил), 45.7 (CH αTrp)), 45.8 (СН₂-пара-метилбензил), 56.8 (Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.9 (C₂ Trp), 126.2 (C₄ фенил), 126.4 (C₃ и C₅ пара-метилбензил), 127.3 (C₉ Trp), 128.7 (C₂, C₃, С₅ и С₆ фенил), 129.8 (C₂ и C₆ пара-метилбензил), 133.0 (C₁ пара-метилбензил), 136.4 (C₈ Trp), 137.5 (C₄ пара-метилбензил), 141.7 (С₁ фенил), 154.8 (Cq триазол), 171.9 (CO Aib).δ (ppm) 21.0 (CH ₃ para-methylbenzyl), 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 24.0 (CH ₂ -

-CH ₂ -phenyl), 28.5 (

-CH ₂ -CH ₂ -phenyl), 29.1 (CH ₂ βTrp), 34.7 (CH ₂ -CH ₂ -

-phenyl), 45.7 (CH αTrp)), 45.8 (CH ₂ -para-methylbenzyl), 56.8 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 118.3 (C ₄ Trp), 118.7 ( C ₅ Trp), 121.3 (C ₆ Trp), 124.9 (C ₂ Trp), 126.2 (C ₄ phenyl), 126.4 (C ₃ and C ₅ para-methylbenzyl), 127.3 (C ₉ Trp), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 129.8 (C ₂ and C ₆ para-methylbenzyl), 133.0 (C ₁ para-methylbenzyl), 136.4 (C ₈ Trp), 137.5 (C ₄ para-methylbenzyl), 141.7 ( C ₁ phenyl), 154.8 (Cq triazole), 171.9 (CO Aib).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methylbenzyl) -4H-1,2, 4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 34):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-индол), 3.32 (2Н, m, СН₂ βTrp), 5.04 (2Н, s,

-пара-метилбензил), 5.16 (1 Н, m, CH αTrp), 6.79-6.86 (4Н, m, СН аr пара-метилбензил), 6.99-7.05 (4Н, m, Н₅ и Н₆ индол, Н₅ и Н₆ Trp), 7.08 (3Н, m, H₂ индол, Н₂ и Н₄ Trp), 7.25-7.30 (3Н, m, Н₄ и Н₇ индол, Н₇ Trp), 8.00 (3Н, brs, NH₂ Aib), 8.94 (1 Н, d, J=8 Hz, NH амид), 10.76 (1 H, s, NH индол), 10.78 (1 H, s, NH индол Trp).δ (ppm) 1.25 (3Н, s, СН ₃ Aib), 1.28 (3Н, s, СН ₃ Aib), 2.23 (3Н, s, С Н ₃ -paramethylbenzyl), 2.84-2.97 (4Н, m,

-

-indole), 3.32 (2H, m, CH ₂ βTrp), 5.04 (2H, s,

-para-methylbenzyl), 5.16 (1 H, m, CH αTrp), 6.79-6.86 (4H, m, CH ar para-methylbenzyl), 6.99-7.05 (4H, m, H ₅ and H ₆ indole, H ₅ and H ₆ Trp), 7.08 (3H, m, H ₂ indole, H ₂ and H ₄ Trp), 7.25-7.30 (3H, m, H ₄ and H ₇ indole, H ₇ Trp), 8.00 (3H, brs, NH ₂ Aib), 8.94 (1 H, d, J = 8 Hz, NH amide), 10.76 (1 H, s, NH indole), 10.78 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-пара-метилбензил), 22.8 (СН₂-СН₂-индол), 23.8 (CH₃ Aib), 23.9 (CH₃ Aib), 25.9 (

-СН₂-индол), 28.5 (CH₂ βTrp), 45.7 (

-пара-метилбензил и СН αTrp), 56.7 (Cq Aib), 109.9 (С₃ Trp), 111.8 (С₇ индол и С₇ Trp), 113.4 (С₃ индол), 118.1 (С₄ Trp), 118.3 (С₄ индол), 118.5 (С₅ индол), 118.7 (С₅ Trp), 120.9 (С₆ индол и С₆ Trp), 121.3 (С₂ индол и С₂ Trp), 126.3 (С₃ и С₅ пapa-метилбензил), 127.2 (С₉ индол), 127.3 (С₉ Trp), 129.8 (С₂ и С₆ пapa-метилбензил), 133.1 (C₁ пapa-метилбензил), 135.8 (С₈ индол, С₈ Trp), 136.4 (С₄ пapa-метилбензил), 154.8 (Cq триазол), 155.0 (Cq триазол), 171.9 (СО Aib).δ (ppm) 21.0 (

-para-methylbenzyl), 22.8 (CH ₂ - C H ₂ -indole), 23.8 (CH ₃ Aib), 23.9 (CH ₃ Aib), 25.9 (

-CH ₂ -indole), 28.5 (CH ₂ βTrp), 45.7 (

-para-methylbenzyl and CH αTrp), 56.7 (Cq Aib), 109.9 (C ₃ Trp), 111.8 (C ₇ indole and C ₇ Trp), 113.4 (C ₃ indole), 118.1 (C ₄ Trp), 118.3 (C ₄ indole), 118.5 (C ₅ indole), 118.7 (C ₅ Trp), 120.9 (C ₆ indole and C ₆ Trp), 121.3 (C ₂ indole and C ₂ Trp), 126.3 (C ₃ and C ₅ para-methylbenzyl ), 127.2 (C ₉ indol), 127.3 (C ₉ Trp), 129.8 (C ₂ and C ₆ para-methylbenzyl), 133.1 (C ₁ para-methylbenzyl), 135.8 (C ₈ indole, C ₈ Trp), 136.4 ( C ₄ papa-methylbenzyl), 154.8 (Cq triazole), 155.0 (Cq triazole), 171.9 (CO Aib).

(R) -N- (1- (4- (4-methylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 37):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.32 (2Н, m, СН₂ βTrp), 5.05 (2Н, s, СН₂-пара-метилбензил), 5.18 (1 Н, m, СН αTrp), 6.75 (2Н, d, J₀=8 Hz, Н₃ и Н₅ пара-метилбензил), 6.82 (1 Н, t, J₀=8 Hz, Н₅ Trp), 6.99 (1 Н, t, J₀=8 Hz, H₆ Trp), 7.02-7.11 (6H, m, H₂ Trp и CHar фенил), 7.15 (1 H, d, J₀=7 Hz, H₄ Trp), 7.20 (2H, d, J₀=7 Hz, H₂ и H₆ пара-метилбензил), 7.28 (1H, d, J₀=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib), 8.93 (1H, d, J=8 Hz, NH амид), 10.77 (1 H, s, NH индол Trp).δ (ppm) 1.25 (3H, s, CH ₃ Aib), 1.28 (3H, s, CH ₃ Aib), 2.23 (3H, s, CH ₃ para-methylbenzyl), 2.83 (4H, m,

-

phenyl), 3.32 (2H, m, CH ₂ βTrp), 5.05 (2H, s, CH ₂ -paramethylbenzyl), 5.18 (1 H, m, CH αTrp), 6.75 (2H, d, J ₀ = 8 Hz, Н ₃ and Н ₅ para-methylbenzyl), 6.82 (1 Н, t, J ₀ = 8 Hz, Н ₅ Trp), 6.99 (1 Н, t, J ₀ = 8 Hz, H ₆ Trp), 7.02- 7.11 (6H, m, H ₂ Trp and CHar phenyl), 7.15 (1 H, d, J ₀ = 7 Hz, H ₄ Trp), 7.20 (2H, d, J ₀ = 7 Hz, H ₂ and H ₆ pair -methylbenzyl), 7.28 (1H, d, J ₀ = 8 Hz, H ₇ Trp), 8.01 (3H, brs, NH ₂ Aib), 8.93 (1H, d, J = 8 Hz, NH amide), 10.77 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-фенил), 29.1 (CH₂ βTrp), 32.7 (

-СН₂-фенил), 45.7 (СН αTrp и СН₂-пара-метилбензил), 56.8 (Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.8 (C₂ Trp), 126.4 (C₃ и C₅ пара-метилбензил), 126.6 (C₄ фенил), 127.3 (C₉ Trp), 128.7 (C₂, C₃, C₅ и C₆ фенил), 129.8 (C₂ и C₆ пара-метилбензил), 133.0 (C₁ пара-метилбензил), 136.4 (C₈ Trp), 137.5 (C₄ пара-метилбензил), 140.9 (С₁ фенил), 154.5 (Cq триазол), 154.9 (Cq триазол), 171.9 (CO амид).δ (ppm) 21.0 (CH ₃ para-methylbenzyl), 23.6 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.5 (CH ₂ -

phenyl), 29.1 (CH ₂ βTrp), 32.7 (

-CH ₂ -phenyl), 45.7 (CH αTrp and CH ₂ -para-methylbenzyl), 56.8 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.8 (C ₂ Trp), 126.4 (C ₃ and C ₅ para-methylbenzyl), 126.6 (C ₄ phenyl), 127.3 (C ₉ Trp), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 129.8 (C ₂ and C ₆ para-methylbenzyl), 133.0 (C ₁ para-methylbenzyl), 136.4 (C ₈ Trp), 137.5 (C ₄ para-methylbenzyl), 140.9 (C ₁ phenyl), 154.5 (Cq triazole), 154.9 (Cq triazole), 171.9 (CO amide).

(R) -N- (1- (5-benzyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 39):

¹ H NMR (300 MHz, DMSO-d ⁶ , 300 K):

-бензил), 5.22 (1 H, s, СН αTrp), 5.35 (2H, s, СН₂-о-пиридил), 6.80 (1 H, t, J₀=8 Hz, H₅ Trp), 6.92 (1 H, t, J₀=8 Hz, H₅ пиридил), 6.97 (1 H, t, J₀=8 Hz, H₆ Trp), 7.04 (1 H, d, J₀=8 Hz, H₄ Trp), 7.07 (1H, d, J=2 Hz, H₂ Trp), 7.10-7.16 (5H, m, CHar бензил), 7.19 (1 H, s, H₃ о-пиридил), 7.26 (1 H, d, J₀=8 Hz, H₇ Trp), 7.57 (1 H, t, J₀=9 Hz, H₄ о-пиридил), 8.16 (3Н, brs, NH₂ Aib), 8.36 (1 H, d, J_αβ=5 Hz, H₆ о-пиридил), 9.01 (1 H, d, J=8 Hz, NH амид), 10.85 (1 H, s, NH индол Trp).δ (ppm) 1.23 (3H, s, CH ₃ Aib), 1.27 (3H, s, CH ₃ Aib), 3.34 (1 H, dd, J = 14 Hz and 6 Hz, CH ₂ βTrp), 3.43 (1 H , dd, J = 14 Hz and 9 Hz, CH ₂ βTrp), 4.13 (2H, s,

-benzyl), 5.22 (1 H, s, СН αTrp), 5.35 (2H, s, СН _2- о-pyridyl), 6.80 (1 H, t, J ₀ = 8 Hz, H ₅ Trp), 6.92 (1 H, t, J ₀ = 8 Hz, H ₅ pyridyl), 6.97 (1 H, t, J ₀ = 8 Hz, H ₆ Trp), 7.04 (1 H, d, J ₀ = 8 Hz, H ₄ Trp) 7.07 (1H, d, J = 2 Hz, H ₂ Trp), 7.10-7.16 (5H, m, CHar benzyl), 7.19 (1 H, s, H ₃ o-pyridyl), 7.26 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 7.57 (1 H, t, J ₀ = 9 Hz, H ₄ o-pyridyl), 8.16 (3H, brs, NH ₂ Aib), 8.36 (1 H, d, J _αβ = 5 Hz, H ₆ o-pyridyl), 9.01 (1 H, d, J = 8 Hz, NH amide), 10.85 (1 H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.4 (CH ₃ Aib), 23.7 (CH ₃ Aib), 28.6 (CH ₂ βTrp), 30.4 (CH ₂ -benzyl), 45.7 (CH αTrp), 47.7 (CH ₂ -o-pyridyl), 56.7 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 118.3 (C ₄ Trp), 118.6 (C ₅ Trp), 121.2 (C ₆ Trp), 121.7 (C ₃ o-pyridyl), 123.3 (C ₅ o-pyridyl), 124.8 (C ₂ Trp), 127.1 (C ₄ benzyl), 127.3 (C ₉ Trp), 128.8 (C ₂ and C ₆ benzyl), 129.0 (C ₃ and C ₅ benzyl), 135.6 (C ₁ benzyl), 136.4 (C ₈ Trp), 137.5 (C ₄ o-pyridyl), 149.5 (C ₆ o-pyridyl), 154.1 (Cq triazole), 154.2 (Cq triazole), 155.7 (C ₂ o-pyridyl ), 172.0 (CO amide).

(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 43):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

пара-этилбензил), 2.83 (4H, m,

-

-фенил), 3.34 (2H, m, CH₂ βTrp), 5.07 (2H, s,

-пара-этилбензил), 5.19 (1 H, m, CH αTrp), 6.77 (2H, d, J₀=8 Hz, H₃ и H₅ пара-этилбензил), 6.81 (1 H, t, J₀=7 Hz, H₅ Trp), 6.99 (1 H, t, J₀=8 Hz, H₆ Trp), 7.05-7.10 (7H, m, CHar фенил, H₂ и H₆ пара-этилбензил), 7.13 (1 H, d, J=2 Hz, H₂ Trp), 7.20 (1 H, d, J₀=7 Hz, H₄ Trp), 7.28 (1H, d, J₀=8 Hz, H₇ Trp), 8.03 (3H, brs, NH₂ Aib), 8.94 (1 H, d, J=8 Hz, NH амид), 10.79 (1 H, s NH индол Trp).δ (ppm) 1.10 (3H, t, J = 8 Hz, C H ₃ -CH ₂ , para-ethylbenzyl), 1.25 (3H, s, CH ₃ Aib), 1.28 (3H, s, CH ₃ Aib), 2.53 (2H, q, J = 8 Hz, CH ₃ -

para-ethylbenzyl), 2.83 (4H, m,

-

phenyl), 3.34 (2H, m, CH ₂ βTrp), 5.07 (2H, s,

-para-ethylbenzyl), 5.19 (1 H, m, CH αTrp), 6.77 (2H, d, J ₀ = 8 Hz, H ₃ and H ₅ para-ethylbenzyl), 6.81 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 6.99 (1 H, t, J ₀ = 8 Hz, H ₆ Trp), 7.05-7.10 (7H, m, CHar phenyl, H ₂ and H ₆ para-ethylbenzyl), 7.13 (1 H , d, J = 2 Hz, H ₂ Trp), 7.20 (1 H, d, J ₀ = 7 Hz, H ₄ Trp), 7.28 (1H, d, J ₀ = 8 Hz, H ₇ Trp), 8.03 ( 3H, brs, NH ₂ Aib), 8.94 (1 H, d, J = 8 Hz, NH amide), 10.79 (1 H, s NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-CH₂ пара-этилбензил), 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 26.5 (

-СН₂-фенил), 28.1 (CH₃-

пара-этилбензил), 29.1 (CH₂ βTrp), 32.7 (СН₂-СН₂-фенил), 45.7 (CH αTrp)), 45.8 (

-пара-этилбензил), 56.8 (Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.9 (C₂ Trp), 126.5 (C₃ и C₅ пара-этилбензил), 126.6 (C₄ фенил), 127.3 (C₉ Trp), 128.6 (C₂ и С₆ пара-этилбензил, C₂, C₃, C₅ и C₆ фенил), 133.1 (С₁ пара-этилбензил), 136.5 (C₈ Trp), 140.8 (С₁ фенил), 143.8 (C₄ пара-этилбензил), 154.6 (Cq триазол), 154.9 (Cq триазол), 171.9 (СО амид).δ (ppm) 15.9 (

-CH ₂ para-ethylbenzyl), 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.5 (

-CH ₂ -phenyl), 28.1 (CH ₃ -

para-ethylbenzyl), 29.1 (CH ₂ βTrp), 32.7 (CH ₂ - C H ₂ phenyl), 45.7 (CH αTrp)), 45.8 (

-para-ethylbenzyl), 56.8 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.9 (C ₂ Trp), 126.5 (C ₃ and C ₅ para-ethylbenzyl), 126.6 (C ₄ phenyl), 127.3 (C ₉ Trp), 128.6 (C ₂ and C ₆ para-ethylbenzyl, C ₂ , C ₃ , C ₅ and C ₆ phenyl), 133.1 (C ₁ para-ethylbenzyl), 136.5 (C ₈ Trp), 140.8 (C ₁ phenyl), 143.8 (C ₄ para-ethylbenzyl), 154.6 (Cq triazole), 154.9 (Cq triazole), 171.9 (CO amide).

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide (Compound 44):

¹ N NMR (300 MHz, DMSO d ⁶ , 300K):

-

-фенил), 3.04 (m, 1 Н, Н₆ пиперидил), 3.13 (m, 1 Н, Н₂ пиперидил), 3.32 (m, 2Н, CH₂ βTrp), 3.66 (s, 3Н, ОСН₃), 4.97 (m, 2Н, СН₂-пара-метоксибензил), 5.23 (m, 1 Н, СН αTrp), 6.70 (s, 4Н, СНаr пара-метоксибензил), 6.87 (t, 1 Н, J₀=8 Hz, Н₅ Trp), 7.00 (m, 2Н, Н₂ и Н₆ Trp), 7.07 (d, 2Н, J₀=8 Hz, Н₂ и Н₆ фенил), 7.14 (d, 1 Н, J₀=7 Hz, Н₄ Trp), 7.18-7.30 (m, 4Н, Н₇ Trp, Н₃, Н₄ и Н₅ фенил), 8.16 и 8.46 (2 m, 2Н, NH пиперидил TFA соль), 8.66 (d, 1Н, J=8 Hz, NH амид), 10.75 (1 Н, s, NH индол Trp).δ (ppm) 1.42 (m, 2H, H ₃ and H ₅ piperidyl), 1.55 (m, 1 H, H ₅ piperidyl), 2.23 (m, 1 H, H ₄ piperidyl), 2.75 (m, 5H, H ₂ piperidyl and

-

phenyl), 3.04 (m, 1 H, H ₆ piperidyl), 3.13 (m, 1 H, H ₂ piperidyl), 3.32 (m, 2H, CH ₂ βTrp), 3.66 (s, 3H, OCH ₃ ), 4.97 (m, 2H, CH ₂ -para-methoxybenzyl), 5.23 (m, 1H, CH αTrp), 6.70 (s, 4H, CHа-para-methoxybenzyl), 6.87 (t, 1 N, J ₀ = 8 Hz, N ₅ Trp), 7.00 (m, 2H, H ₂ and H ₆ Trp), 7.07 (d, 2H, J ₀ = 8 Hz, H ₂ and H ₆ phenyl), 7.14 (d, 1 H, J ₀ = 7 Hz , H ₄ Trp), 7.18-7.30 (m, 4H, H ₇ Trp, H ₃ , H ₄ and H ₅ phenyl), 8.16 and 8.46 (2 m, 2H, NH piperidyl TFA salt), 8.66 (d, 1H, J = 8 Hz, NH amide), 10.75 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-СН₂-фенил), 29.2 (CH₂ βTrp), 32.7 (СН₂-

-фенил), 38.7 (C₄ пиперидил), 42.7 (C₂ и C₆ пиперидил), 44.7 (CH Trp), 45.3 (СН₂-пара-метоксибензил), 55.5 (OCH₃), 110.2 (C₃ Trp), 111.7 (C₇ Trp), 114.4 (C₃ и C₅ пара-метоксибензил), 118.5 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.4 (C₂ Trp), 126.5 (C₂ и C₆ фенил), 127.5 (C₉ Trp), 127.8 (С₁, C₂ и C₆ пара-метоксибензил), 128.7 (C₃, C₄ и C₅ фенил), 136.4 (C₈ Trp), 140.8 (С₁ фенил), 155.3 (Cq триазол), 155.4 (Cq триазол), 159.1 (C₄ пара-метоксибензил), 173.1 (CO амид).δ (ppm) 24.9 (C ₃ piperidyl), 25.4 (C ₅ piperidyl), 26.5 (

-CH ₂ -phenyl), 29.2 (CH ₂ βTrp), 32.7 (CH ₂ -

-phenyl), 38.7 (C ₄ piperidyl), 42.7 (C ₂ and C ₆ piperidyl), 44.7 (CH Trp), 45.3 (CH ₂ para-methoxybenzyl), 55.5 (OCH ₃ ), 110.2 (C ₃ Trp), 111.7 (C ₇ Trp), 114.4 (C ₃ and C ₅ para-methoxybenzyl), 118.5 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.4 (C ₂ Trp), 126.5 (C ₂ and C ₆ phenyl), 127.5 (C ₉ Trp), 127.8 (C ₁ , C ₂ and C ₆ para-methoxybenzyl), 128.7 (C ₃ , C ₄ and C ₅ phenyl), 136.4 (C ₈ Trp), 140.8 (C ₁ phenyl), 155.3 (Cq triazole), 155.4 (Cq triazole), 159.1 (C ₄ para-methoxybenzyl), 173.1 (CO amide).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) piperidin-4-carboxamide (Compound 45):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-индол), 3.06 (m, 2H, H₂ и H₆ пиперидил), 3.32 (m, 2H, CH₂ βTrp), 3.65 (s, 3H, OCH₃), 4.94 (s, 2H, СН₂-пара-метоксибензил), 5.22 (m, 1 H, СН αTrp), 6.68 (s, 4H, CHar пара-метоксибензил), 6.87 (m, 3Н, H₅ и H₆ Trp, H₅ индол), 6.98 (m, 4H, H₂ и H₆ индол, H₂ и H₄ Trp), 7.20-7.33 (m, 3H, H₄ и H₇ индол, H₇ Trp), 8.15 и 8.46 (2 m, 2H, NH пиперидил TFA соль), 8.64 (d, 1 H, J=8 Hz, NH амид), 10.74 (s, 2H, NH индол и NH индол Trp).δ (ppm) 1.41 (m, 2H, H ₃ and H ₅ piperidyl), 1.54 (dd, 1 H, J = 13 Hz and 2 Hz, H ₅ piperidyl), 2.23 (m, 1 H, H ₄ piperidyl), 2.72 (m, 2H, H ₂ and H ₆ piperidyl), 2.77-2.93 (m, 4H,

-

-indole), 3.06 (m, 2H, H ₂ and H ₆ piperidyl), 3.32 (m, 2H, CH ₂ βTrp), 3.65 (s, 3H, OCH ₃ ), 4.94 (s, 2H, CH ₂ -para- methoxybenzyl), 5.22 (m, 1 H, CH αTrp), 6.68 (s, 4H, CHar para-methoxybenzyl), 6.87 (m, 3H, H ₅ and H ₆ Trp, H ₅ indole), 6.98 (m, 4H, H ₂ and H ₆ indole, H ₂ and H ₄ Trp), 7.20-7.33 (m, 3H, H ₄ and H ₇ indole, H ₇ Trp), 8.15 and 8.46 (2 m, 2H, NH piperidyl TFA salt), 8.64 (d, 1 H, J = 8 Hz, NH amide); 10.74 (s, 2H, NH indole and NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-индол), 24.9 (C₃ пиперидил), 25.4 (C₅ пиперидил), 26.0 (

-СН₂-индол), 29.3 (CH₂ βTrp), 39.1 (C₄ пиперидил), 42.7 (C₂ и C₆ пиперидил), 44.7 (СН αTrp), 45.3 (СН₂-пара-метоксибензил), 55.5 (OCH₃), 109.5 (C₃ Trp), 111.7 (C₇ индол и C₇ Trp), 113.5 (C₃ индол), 114.4 (C₃ и C₅ пара-метоксибензил), 118.5 (C₄ индол и C₄ Trp), 118.6 (C₅ индол и C₅ Trp), 121.2 (C₆ индол), 121.3 (C₆ Trp), 122.9 (C₂ индол и C₂ Trp), 127.2 (C₉ индол), 127.5 (C₉ Trp, C₂ и C₆ пара-метоксибензил), 127.9 (С₁ пара-метоксибензил), 136.4 (C₈ Trp), 136.6 (C₈ индол), 154.9 (Cq триазол), 155.2 (Cq триазол), 159.0 (C₄ пара-метоксибензил), 173.0 (CO амид).δ (ppm) 22.9 (CH ₂ -

-indole), 24.9 (C ₃ piperidyl), 25.4 (C ₅ piperidyl), 26.0 (

-CH ₂ -indole), 29.3 (CH ₂ βTrp), 39.1 (C ₄ piperidyl), 42.7 (C ₂ and C ₆ piperidyl), 44.7 (CH αTrp), 45.3 (CH ₂ -paramethoxybenzyl), 55.5 (OCH ₃ ), 109.5 (C ₃ Trp), 111.7 (C ₇ indole and C ₇ Trp), 113.5 (C ₃ indole), 114.4 (C ₃ and C ₅ para-methoxybenzyl), 118.5 (C ₄ indole and C ₄ Trp) , 118.6 (C ₅ indole and C ₅ Trp), 121.2 (C ₆ Indole), 121.3 (C ₆ Trp), 122.9 (C ₂ indole and C ₂ Trp), 127.2 (C ₉ indole), 127.5 (C ₉ Trp, C ₂ and C ₆ para-methoxybenzyl), 127.9 (C ₁ para-methoxybenzyl), 136.4 (C ₈ Trp), 136.6 (C ₈ indole), 154.9 (Cq triazole), 155.2 (Cq triazole), 159.0 (C ₄ pair -methoxybenzyl), 173.0 (CO amide).

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide (Compound 50):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-фенил), 3.26 (1 H, dd, J=14 Hz и 7 Hz, CH₂ βTrp), 3.39 (m, 3Н, CH₂ βTrp и

-NH₂), 3.65 (s, 3Н, OCH₃), 4.95 (m, 2Н, СН₂-пара-метоксибензил), 5.20 (m, 1 Н, CH αTrp), 6.63 (s, 4H, CHar пара-метоксибензил), 6.86 (t, 1 Н, J₀=7 Hz, Н₅ Trp), 6.99 (s, 1 H, H₂ Trp), 7.02 (t, 1 H, J₀=7 Hz, H₆ Trp), 7.10 (m, 2H, H₂ и H₆ фенил), 7.15 (d, 1 H, J₀=7 Hz, H₄ Trp), 7.23 (m, 3Н, H₃, H₄ и H₅ Trp), 7.31 (d, 1 H, J₀=8 Hz, H₇ Trp), 7.95 (brs, 3H, NH₂ Gly, TFA соль), 9.20 (d, 1 H, J=8 Hz, NH амид), 10.82 (s, 1 H, NH индол Trp).δ (ppm) 2.78 (m, 4H,

-

phenyl), 3.26 (1 H, dd, J = 14 Hz and 7 Hz, CH ₂ βTrp), 3.39 (m, 3H, CH ₂ βTrp and

-NH ₂ ), 3.65 (s, 3H, OCH ₃ ), 4.95 (m, 2H, CH ₂ -para-methoxybenzyl), 5.20 (m, 1H, CH αTrp), 6.63 (s, 4H, CHar p-methoxybenzyl ), 6.86 (t, 1 H, J ₀ = 7 Hz, H ₅ Trp), 6.99 (s, 1 H, H ₂ Trp), 7.02 (t, 1 H, J ₀ = 7 Hz, H ₆ Trp), 7.10 (m, 2H, H ₂ and H ₆ phenyl), 7.15 (d, 1 H, J ₀ = 7 Hz, H ₄ Trp), 7.23 (m, 3H, H ₃ , H ₄ and H ₅ Trp), 7.31 (d, 1 H, J ₀ = 8 Hz, H ₇ Trp), 7.95 (brs, 3H, NH ₂ Gly, TFA salt), 9.20 (d, 1 H, J = 8 Hz, NH amide), 10.82 (s , 1 H, NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-NH₂), 45.3 (СН₂-пара-метоксибензил), 45.4 (CH αTrp), 55.4 (OCH₃), 109.7 (C₃ Trp), 111.8 (C₇ Trp), 114.5 (C₃ и C₅ пара-метоксибензил), 118.3 (C₄ Trp), 118.9 (C₅ Trp), 121.4 (C₆ Trp), 124.6 (C₂ Trp), 126.5 (C₂ и C₆ фенил), 127.3 (C₉ Trp), 127.7 (С₁ пара-метоксибензил), 127.8 (C₂ и C₆ пара-метоксибензил), 128.7 (C₃, С₄ и С₅ фенил), 136.4 (C₈ Trp), 140.9 (С₁ фенил), 154.3 (Cq триазол), 154.7 (Cq триазол), 159.0 (C₄ пара-метоксибензил), 166.1 (CO амид).δ (ppm) 26.5 ( C H ₂ -CH ₂ phenyl), 29.8 (CH ₂ βTrp), 32.7 (CH ₂ - C H ₂ phenyl), 39.0 (

-NH ₂ ), 45.3 (CH ₂ -para-methoxybenzyl), 45.4 (CH αTrp), 55.4 (OCH ₃ ), 109.7 (C ₃ Trp), 111.8 (C ₇ Trp), 114.5 (C ₃ and C ₅ para- methoxybenzyl), 118.3 (C ₄ Trp), 118.9 (C ₅ Trp), 121.4 (C ₆ Trp), 124.6 (C ₂ Trp), 126.5 (C ₂ and C ₆ phenyl), 127.3 (C ₉ Trp), 127.7 ( C ₁ para-methoxybenzyl), 127.8 (C ₂ and C ₆ para-methoxybenzyl), 128.7 (C ₃ , C ₄ and C ₅ phenyl), 136.4 (C ₈ Trp), 140.9 (C ₁ phenyl), 154.3 (Cq triazole ), 154.7 (Cq triazole), 159.0 (C ₄ para-methoxybenzyl), 166.1 (CO amide).

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide (Compound 51):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-фенил), 3.37 (m, 2Н, CH₂ βTrp), 3.64 (s, 3Н, OCH₃), 3.74 (m, 2Н, СН₂-о-пиридил), 5.03 (m, 2Н,

-пара-метоксибензил), 5.24 (m, 1 Н, CH αTrp), 6.65 (s, 4Н, СНаr пара-метоксибензил), 6.85 (t, 1 Н, J₀=7 Hz, Н₅ Trp), 7.01 (m, 2Н, Н₂ и Н₆ Trp), 7.08 (d, 2Н, J₀=7 Hz, Н₂ и Н₆ фенил), 7.15 (d, 1 Н, J₀=7 Hz, Н₄ Trp), 7.21 (m, 3Н, Н₃, Н₄ и Н₅ фенил), 7.27-7.36 (m, 2Н, Н₇ Trp и Н₃ о-пиридил), 7.58 (t, 1 Н, J=6 Hz, Н₅ о-пиридил), 8.04 (t, 1Н, J₀=8 Hz, H₄ о-пиридил), 8.62 (d, 1 Н, Jαβ=5 Hz, H₆ о-пиридил), 9.17 (d, 1 Н, J=8 Hz, NH амид), 10.81 (s, 1H, NH индол Trp).δ (ppm) 2.77-2.88 (m, 4H,

-

phenyl), 3.37 (m, 2H, CH ₂ βTrp), 3.64 (s, 3H, OCH ₃ ), 3.74 (m, 2H, CH ₂ -o-pyridyl), 5.03 (m, 2H,

-para-methoxybenzyl), 5.24 (m, 1 N, CH αTrp), 6.65 (s, 4Н, СНа para-methoxybenzyl), 6.85 (t, 1 Н, J ₀ = 7 Hz, Н ₅ Trp), 7.01 (m , 2H, H ₂ and H ₆ Trp), 7.08 (d, 2H, J ₀ = 7 Hz, H ₂ and H ₆ phenyl), 7.15 (d, 1 H, J ₀ = 7 Hz, H ₄ Trp), 7.21 (m, 3H, H ₃ , H ₄ and H ₅ phenyl), 7.27-7.36 (m, 2H, H ₇ Trp and H ₃ o-pyridyl), 7.58 (t, 1 H, J = 6 Hz, H ₅ o -pyridyl), 8.04 (t, 1Н, J ₀ = 8 Hz, H ₄ о-pyridyl), 8.62 (d, 1 Н, Jαβ = 5 Hz, H ₆ о-pyridyl), 9.17 (d, 1 Н, J = 8 Hz, NH amide), 10.81 (s, 1H, NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-СН₂-фенил), 29.2 (CH₂ βTrp), 32.4 (

-СН₂-фенил), 41.7 (СН₂-O-пиридил), 45.3 (CH αTrp), 45.7 (СН₂-пара-метоксибензил), 55.5 (OCH₃), 109.7 (C₃ Trp), 111.8 (C₇ Trp), 114.4 (C₃ и C₅ пара-метоксибензил), 118.4 (C₄ Trp), 118.8 (C₅ Trp), 121.4 (C₆ Trp), 124.1 (C₃ о-пиридил), 124.6 (C₂ Trp), 126.4 (C₅ о-пиридил), 126.6 (C₂ и C₆ фенил), 127.2 (C₉ Trp), 127.4 (C₁ пара-метоксибензил), 127.9 (C₂ и C₆ пара-метоксибензил), 128.7 (C₃, C₄ и C₅ фенил), 136.4 (C₈ Trp), 140.5 (C₁ фенил), 142.1 (C₄ о-пиридил), 145.3 (C₆ о-пиридил), 153.0 (C₂ о-пиридил), 154.5 (Cq триазол), 155.3 (Cq триазол), 159.1 (C₄ пара-метоксибензил), 167.9 (CO амид).δ (ppm) 26.4 (

-CH ₂ -phenyl), 29.2 (CH ₂ βTrp), 32.4 (

- C H ₂ -phenyl), 41.7 (CH ₂ -O-pyridyl), 45.3 (CH ₂ α-Trp), 45.7 (CH ₂ -paramethoxybenzyl), 55.5 (OCH ₃ ), 109.7 (C ₃ Trp), 111.8 (C ₇ Trp), 114.4 (C ₃ and C ₅ para-methoxybenzyl), 118.4 (C ₄ Trp), 118.8 (C ₅ Trp), 121.4 (C ₆ Trp), 124.1 (C ₃ o-pyridyl), 124.6 (C ₂ Trp), 126.4 (C ₅ o-pyridyl), 126.6 (C ₂ and C ₆ phenyl), 127.2 (C ₉ Trp), 127.4 (C ₁ para-methoxybenzyl), 127.9 (C ₂ and C ₆ para-methoxybenzyl), 128.7 (C ₃ , C ₄ and C ₅ phenyl), 136.4 (C ₈ Trp), 140.5 (C ₁ phenyl), 142.1 (C ₄ o-pyridyl), 145.3 (C ₆ o-pyridyl), 153.0 (C ₂ o -pyridyl), 154.5 (Cq triazole), 155.3 (Cq triazole), 159.1 (C ₄ para-methoxybenzyl), 167.9 (CO amide).

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide (Compound 64):

¹ H NMR (300 MHz1 DMSO d ⁶ , 300 K):

-СН₂-фенил), 2.90 (m, 2H, СН₂-

-фенил), 3.48 (m, 2H, CH₂ βTrp), 3.57 (s, 3H, OCH₃), 3.61 (s, 3H, OCH₃), 4.97 (d, 1 H, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.09 (d, 1 H, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.56 (m, 1 H, CH αTrp)), 6.18 (dd, 1 H, J₀=8 Hz и J_m=2 Hz, H₅ о,пара-диметоксибензил), 6.41 (d, 1 H, J_m=2 Hz, H₃ о,пара-диметоксибензил), 6.55 (d, 1 H, J₀=8 Hz, Н₆ о,пара-диметоксибензил), 6.87 (t, 1H, J₀=8 Hz, H₅ Trp), 7.01 (t, 1 H, J₀=8 Hz, H₆ Trp), 7.08 (m, 3H, H₂ Trp, Н₂и H₆ фенил), 7.14 (d, 1 H, J₀=7 Hz, H₄ Trp), 7.19-7.31 (m, 4H, H₇ Trp, H₃, H₄ и H₅ фенил), 7.56 (t, 1H, J=8 Hz, NH амид), 7.91 (m, 2H, H₄ и H₅ о-пиридил), 8.57 (d, 1 H, Jαβ=5 Hz, H₆ о-пиридил), 9.16 (d, 1 H, J₀=8 Hz, H₃ о-пиридил), 10.80 (s, 1 H, NH индол Trp).δ (ppm) 2.83 (m, 2H,

-CH ₂ -phenyl), 2.90 (m, 2H, CH ₂ -

phenyl), 3.48 (m, 2H, CH ₂ βTrp), 3.57 (s, 3H, OCH ₃ ), 3.61 (s, 3H, OCH ₃ ), 4.97 (d, 1 H, J = 17 Hz, CH ₂ - o, para-dimethoxybenzyl), 5.09 (d, 1 H, J = 17 Hz, CH ₂ -o, para-dimethoxybenzyl), 5.56 (m, 1 H, CH αTrp)), 6.18 (dd, 1 H, J ₀ = 8 Hz and J _m = 2 Hz, H ₅ about, para-dimethoxybenzyl), 6.41 (d, 1 H, J _m = 2 Hz, H ₃ about, para-dimethoxybenzyl), 6.55 (d, 1 H, J ₀ = 8 Hz, H ₆ °, para-dimethoxybenzyl), 6.87 (t, 1H, J ₀ = 8 Hz, H ₅ Trp), 7.01 (t, 1 H, J ₀ = 8 Hz, H ₆ Trp), 7.08 ( m, 3H, H ₂ Trp, H ₂ and H ₆ phenyl), 7.14 (d, 1 H, J ₀ = 7 Hz, H ₄ Trp), 7.19-7.31 (m, 4H, H ₇ Trp, H ₃ , H ₄ and H ₅ phenyl), 7.56 (t, 1H, J = 8 Hz, NH amide), 7.91 (m, 2H, H ₄ and H ₅ o-pyridyl), 8.57 (d, 1 H, Jαβ = 5 Hz, H ₆ o-pyridyl), 9.16 (d, 1 H, J ₀ = 8 Hz, H ₃ o-pyridyl), 10.80 (s, 1 H, NH indol Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-СН₂-фенил), 28.8 (CH₂ βTrp), 32.1 (СН₂-

-фенил), 43.0 (СН₂-о,пара-диметоксибензил), 45.5 (CH αTrp), 55.6 (OCH₃), 55.8 (OCH₃), 98.9 (С₃ о,пара-диметоксибензил), 105.0 (С₅ о,пара-диметоксибензил), 109.5 (С₃ Trp), 111.8 (С₇ Trp), 114.4 (C₁, о,пара-диметоксибензил), 118.4 (С₄ Trp), 118.8 (С₅ Trp), 121.4 (С₆ Trp), 122.4 (С₃ о-пиридил), 124.4 (С₂ Trp), 126.7 (С₆ о,пара-диметоксибензил), 127.2 (С₅ о-пиридил), 127.5 (С₉ Trp), 128.6-128.8 (С₂, С₃, С₄, С₅ и С₆ фенил), 136.4 (С₈ Trp), 138.1 (С₄ о-пиридил), 140.2 (С, фенил), 148.8 (С₆ о-пиридил), 149.3 (С₂ о-пиридил), 155.2 (Cq триазол), 155.4 (Cq триазол), 157.9 (С₂ о,пара-диметоксибензил), 161.0 (С₄ о,пара-диметоксибензил), 163.9 (СО амид).δ (ppm) 26.2 (

-CH ₂ -phenyl), 28.8 (CH ₂ βTrp), 32.1 (CH ₂ -

phenyl), 43.0 (CH ₂ -o, para-dimethoxybenzyl), 45.5 (CH αTrp), 55.6 (OCH ₃ ), 55.8 (OCH ₃ ), 98.9 (С ₃ о, para-dimethoxybenzyl), 105.0 (С ₅ о , para-dimethoxybenzyl), 109.5 (C ₃ Trp), 111.8 (C ₇ Trp), 114.4 (C ₁ , о, para-dimethoxybenzyl), 118.4 (C ₄ Trp), 118.8 (C ₅ Trp), 121.4 (C ₆ Trp), 122.4 (C ₃ o-pyridyl), 124.4 (C ₂ Trp), 126.7 (C ₆ o, para-dimethoxybenzyl), 127.2 (C ₅ o-pyridyl), 127.5 (C ₉ Trp), 128.6-128.8 ( C ₂ , C ₃ , C ₄ , C ₅ and C ₆ phenyl), 136.4 (C ₈ Trp), 138.1 (C ₄ o-pyridyl), 140.2 (C, phenyl), 148.8 (C ₆ o-pyridyl), 149.3 (C ₂ o-pyridyl), 155.2 (Cq triazole), 155.4 (Cq triazole), 157.9 (C ₂ o, para-dimethoxybenzyl), 161.0 (C ₄ o, para-dimethoxybenzyl), 163.9 (CO amide).

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide (Compound 66):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-фенил), 3.51 (m, 2Н, СН₂ βTrp), 3.58 (s, 3Н, ОСН₃), 3.59 (s, 3Н, ОСН₃), 4.97 (d, 1 Н, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.08 (d, 1 Н, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.56 (s, 1 Н, СН αTrp), 6.10 (dd, 1 Н, J₀=8 Hz и J_m=2 Hz, Н₅ о,пара-диметоксибензил), 6.36 (d, 1 Н, J_m=2 Hz, Н₃ о,пара-диметоксибензил), 6.40 (d, 1 Н, J₀=8 Hz, Н₆ о,пара-диметоксибензил), 6.87 (t, 1 Н, J₀=8 Hz, Н₅ Trp), 7.00 (t, 1H, J₀=7 Hz, H₆ Trp), 7.09 (m, 3H, H₂ Trp, H₂ и H₆ фенил), 7.15 (d, 1H, J₀=7 Hz, H₄ Trp), 7.19-7.28 (m, 3Н, H₃, H₄ и H₅ фенил), 7.36 (d, 1 Н, J₀=8 Hz, H₇ Trp), 8.61 (t, 1 H, J=2 Hz, H₃ о-пиразинил), 8.78 (d, 1 H, J=2 Hz, H₅ о-пиразинил), 8.94 (d, 1H, J=1 Hz, H₆ о-пиразинил),δ (ppm) 2.87 (m, 4H,

-

phenyl), 3.51 (m, 2H, CH ₂ βTrp), 3.58 (s, 3H, OCH ₃ ), 3.59 (s, 3H, OCH ₃ ), 4.97 (d, 1 H, J = 17 Hz, CH ₂ - о, para-dimethoxybenzyl), 5.08 (d, 1 Н, J = 17 Hz, СН ₂ -о, para-dimethoxybenzyl), 5.56 (s, 1 Н, СН αTrp), 6.10 (dd, 1 Н, J ₀ = 8 Hz and J _m = 2 Hz, Н ₅ о, para-dimethoxybenzyl), 6.36 (d, 1 Н, J _m = 2 Hz, Н ₃ о, para-dimethoxybenzyl), 6.40 (d, 1 Н, J ₀ = 8 Hz, Н ₆ о, para-dimethoxybenzyl), 6.87 (t, 1 Н, J ₀ = 8 Hz, Н ₅ Trp), 7.00 (t, 1H, J ₀ = 7 Hz, H ₆ Trp), 7.09 (m , 3H, H ₂ Trp, H ₂ and H ₆ phenyl), 7.15 (d, 1H, J ₀ = 7 Hz, H ₄ Trp), 7.19-7.28 (m, 3H, H ₃ , H ₄ and H ₅ phenyl) , 7.36 (d, 1 H, J ₀ = 8 Hz, H ₇ Trp), 8.61 (t, 1 H, J = 2 Hz, H ₃ o-pyrazinyl), 8.78 (d, 1 H, J = 2 Hz, H ₅ o-pyrazinyl), 8.94 (d, 1H, J = 1 Hz, H ₆ o-pyrazinyl),

9.26 (d, 1 H, J = 8 Hz, NH amide); 10.78 (s, 1 H, NH indol Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-СН₂-фенил), 28.4 (CH₂ βTrp), 32.1 (

-СН₂-фенил), 42.9 (СН₂-о,пара-диметоксибензил), 45.5 (CH αTrp)), 55.5 (OCH₃), 55.8 (OCH₃), 98.7 (C₃ о,пара-диметоксибензил), 104.9 (C₅ о,пара-диметоксибензил), 109.7 (C₃ о,пара-диметоксибензил), 111.8 (C₇ Trp), 114.5 (С₁ о,пара-диметоксибензил), 118.5 (C₄ Trp), 118.8 (C₅ Trp), 121.4 (C₆ Trp), 124.4 (C₂ Trp), 126.7 (C₆ о,пара-диметоксибензил), 127.5 (C₉ Trp), 128.1 (C₄ фенил), 128.7-128.8 (C₂, C₃, C₅ и C₆ фенил), 136.4 (C₈ Trp), 140.3 (C₁ фенил), 141.2 (C₆ о,пара-диметоксибензил), 144.2 (C₂ о-пиразинил), 144.3 (C₃ о-пиразинил), 146.8 (C₅ о-пиразинил), 155.2 (Cqs триазол), 157.7 (C₂ о,пара-диметоксибензил), 160.7 (CO амид), 162.9 (C₄ о,пара-диметоксибензил).δ (ppm) 26.1 (

-CH ₂ -phenyl), 28.4 (CH ₂ βTrp), 32.1 (

-CH ₂ -phenyl), 42.9 (CH ₂ -o, para-dimethoxybenzyl), 45.5 (CH αTrp)), 55.5 (OCH ₃ ), 55.8 (OCH ₃ ), 98.7 (C ₃ о, para-dimethoxybenzyl), 104.9 (C ₅ o, para-dimethoxybenzyl), 109.7 (C ₃ o, para-dimethoxybenzyl), 111.8 (C ₇ Trp), 114.5 (C ₁ o, para-dimethoxybenzyl), 118.5 (C ₄ Trp), 118.8 (C ₅ Trp), 121.4 (C ₆ Trp), 124.4 (C ₂ Trp), 126.7 (C ₆ about, para-dimethoxybenzyl), 127.5 (C ₉ Trp), 128.1 (C ₄ phenyl), 128.7-128.8 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 136.4 (C ₈ Trp), 140.3 (C ₁ phenyl), 141.2 (C ₆ o, para-dimethoxybenzyl), 144.2 (C ₂ o-pyrazinyl), 144.3 (C ₃ o- pyrazinyl), 146.8 (C ₅ o-pyrazinyl), 155.2 (Cqs triazole), 157.7 (C ₂ o, para-dimethoxybenzyl), 160.7 (CO amide), 162.9 (C ₄ o, para-dimethoxybenzyl).

(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazole -3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide (Compound 70):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-индол), 3.06 (t, 2Н, J=6 Hz, H₅ Pro), 3.28 (m, 2H, CH₂ βTrр), 3.40 (s, 3H, OCH₃), 3.80 (s, 3H, OCH₃), 3.80 (m, 1H, CH αPro), 4.80 (d, 1 H, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.4 (d, 1 H, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.1 (m, 1 H, CH αTrp), 6.26 (dd, 1 H, J₀=8 Hz и J_m=2 Hz, H₅ о,пара-диметоксибензил), 6.38 (d, 1 H, J₀=8 Hz, H6 о,пара-диметоксибензил), 6.53 (d, 1 H, J_m=2Hz, H₃ о,пара-диметоксибензил), 6.84 (t, 1 H, H₅ индол), 6.91 (t, 1 H, J₀=8 Hz, H₅ Trp), 6.93-7.07 (m, 4H, H₂ и H₆ индол, H₂ и H₆ Trp), 7.16 (d, 1 H, J₀=8 Hz, H₄ Trp), 7.29 (m, 3Н, H₄ и H₇ индол, H₇ Trp), 8.39 и 9.10 (2 m, 2H, NH Pro TFA соль), 9.22 (d, 1 H, J=8 Hz, NH амид), 10.76 (s, 1H, NH индол), 10.80 (s, 1H, NH индол Trp).δ (ppm) 1.40 (m, 1H, H ₃ Pro), 1.53 (m, 1 H, H ₄ Pro), 1.71 (m, 1 H, H ₄ Pro), 2.09 (m, 1H, H ₃ Pro), 2.90 (m, 4H,

-

-indole), 3.06 (t, 2H, J = 6 Hz, H ₅ Pro), 3.28 (m, 2H, CH ₂ βTrp), 3.40 (s, 3H, OCH ₃ ), 3.80 (s, 3H, OCH ₃ ) , 3.80 (m, 1H, CH αPro), 4.80 (d, 1 H, J = 17 Hz, CH ₂ -o, para-dimethoxybenzyl), 5.4 (d, 1 H, J = 17 Hz, CH ₂ -o, para-dimethoxybenzyl), 5.1 (m, 1 H, CH αTrp), 6.26 (dd, 1 H, J ₀ = 8 Hz and J _m = 2 Hz, H ₅ about, para-dimethoxybenzyl), 6.38 (d, 1 H , J ₀ = 8 Hz, H6 about, para-dimethoxybenzyl), 6.53 (d, 1 H, J _m = 2Hz, H ₃ about, para-dimethoxybenzyl), 6.84 (t, 1 H, H ₅ indole), 6.91 ( t, 1 H, J ₀ = 8 Hz, H ₅ Trp), 6.93-7.07 (m, 4H, H ₂ and H ₆ indole, H ₂ and H ₆ Trp), 7.16 (d, 1 H, J ₀ = 8 Hz, H ₄ Trp), 7.29 (m, 3H, H ₄ and H ₇ indole, H ₇ Trp), 8.39 and 9.10 (2 m, 2H, NH Pro TFA salt), 9.22 (d, 1 H, J = 8 Hz, NH amide), 10.76 (s, 1H, NH indole), 10.80 (s, 1H, NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-индол), 23.5 (C₄ Pro), 25.8 (

-СН₂-индол), 29.6 (CH₂ βTrp), 29.8 (C₃ Pro), 41.9 (СН₂-о,пара-диметоксибензил), 45.2 (СН αTrp), 46.0 (C₅ Pro), 55.7 (OCH₃), 55.9 (OCH₃), 59.3 (CH αPro), 99.0 (C₃ о,пара-диметоксибензил), 105.1 (C₅ о,пара-диметоксибензил), 109.7 (C₃ Trp), 111.8 (C₇ индол и C₇ Trp), 113.4 (C₃ индол), 115.6 (С, о,пара-диметоксибензил), 118.4 (C₄ индол и C₄Trp), 118.7 (С₅ индол и С₅Trp), 121.4 (С₆ индол и С₆ Trp), 123.0 (С₂ индол и С₂ Trp), 127.2 (С₉ индол), 127.3 (С₉ Trp), 128.1 (С₆ о,пара-диметоксибензил), 136.5 (С₈ Trp), 136.6 (С₈ индол), 155.0 (Cq триазол), 157.8 (С₂ о,пара-диметоксибензил), 160.9 (С₄ о,пара-диметоксибензил), 168.1 (СО амид).δ (ppm) 22.9 (CH ₂ -

-indole), 23.5 (C ₄ Pro), 25.8 (

-CH ₂ -indole), 29.6 (CH ₂ βTrp), 29.8 (C ₃ Pro), 41.9 (CH ₂ -O, para-dimethoxybenzyl), 45.2 (CH αTrp), 46.0 (C ₅ Pro), 55.7 (OCH ₃ ), 55.9 (OCH ₃ ), 59.3 (CH αPro), 99.0 (C ₃ о, para-dimethoxybenzyl), 105.1 (C ₅ о, para-dimethoxybenzyl), 109.7 (C ₃ Trp), 111.8 (C ₇ indole and C ₇ Trp), 113.4 (C ₃ indole), 115.6 (C, o, para-dimethoxybenzyl), 118.4 (C ₄ indole and C ₄ Trp), 118.7 (C ₅ indole and C ₅ Trp), 121.4 (C ₆ indole and С ₆ Trp), 123.0 (С ₂ indole and С ₂ Trp), 127.2 (С ₉ indole), 127.3 (С ₉ Trp), 128.1 (С ₆ о, para-dimethoxybenzyl), 136.5 (С ₈ Trp), 136.6 ( _C8 indole), 155.0 (Cq triazole), 157.8 (C ₂ O vapor-dimethoxybenzyl), 160.9 _(C4 o, vapor-dimethoxybenzyl), 168.1 (CO amide).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) pyrazin-2-carboxamide (Compound 71):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-СН₂-индол), 3.10 (m, 2Н, СН₂-

-индол), 3.51 (m, 2Н, СН₂ βTrp), 3.55 (s, 3Н, ОСН₃), 3.57 (s, 3Н, ОСН₃), 5.15 (d, 2Н, J=7 Hz, СН₂-о,пара-диметоксибензил), 5.63 (m, 1 Н, СН αTrp), 6.08 (dd, 1Н, J₀=8 Hz и J_m=2 Hz, H₅ о,пара-диметоксибензил), 6.35 (d, 1 Н, J_m=2 Hz, H₃ о,пара-диметоксибензил), 6.53 (d, 1 Н, J₀=8 Hz, H₆ о,пара-диметоксибензил), 6.89 (m, 2Н, Н₅ индол и Н₅ Trp), 6.99 (m, 2Н, Н₆ индол и Н₆ Trp), 7.08 (m, 2Н, Н₂ индол и Н₂ Trp), 7.29 (m, 3Н, Н₄ Trp, Н₄ и Н₇ индол), 7.41 (d, 1 Н, J₀=8 Hz, Н₇ Trp), 8.61 (t, 1 Н, J=2 Hz, H₃ о-пиразин), 8.79 (d, 1Н, J=2 Hz, H₅ о-пиразин), 8.94 (d, 1 Н, J=1 Hz, H₆ о-пиразин), 9.43 (d, 1 Н, J=8 Hz, NH амид), 10.84 (s, 2H, NH индол и NH индол Trp).δ (ppm) 3.01 (m, 2H,

-CH ₂ -indole), 3.10 (m, 2H, CH ₂ -

-indole), 3.51 (m, 2H, CH ₂ βTrp), 3.55 (s, 3H, OCH ₃ ), 3.57 (s, 3H, OCH ₃ ), 5.15 (d, 2H, J = 7 Hz, CH ₂ , para-dimethoxybenzyl), 5.63 (m, 1 H, СН αTrp), 6.08 (dd, 1Н, J ₀ = 8 Hz and J _m = 2 Hz, H ₅ о, para-dimethoxybenzyl), 6.35 (d, 1 N , J _m = 2 Hz, H ₃ about, para-dimethoxybenzyl), 6.53 (d, 1 N, J ₀ = 8 Hz, H ₆ about, para-dimethoxybenzyl), 6.89 (m, 2H, H ₅ indole and H ₅ Trp), 6.99 (m, 2H, H ₆ indole and H ₆ Trp), 7.08 (m, 2H, H ₂ indole and H ₂ Trp), 7.29 (m, 3H, H ₄ Trp, H ₄ and H ₇ indole) , 7.41 (d, 1 H, J ₀ = 8 Hz, H ₇ Trp), 8.61 (t, 1 H, J = 2 Hz, H ₃ o-pyrazine), 8.79 (d, 1 H, J = 2 Hz, H ₅ o-pyrazine), 8.94 (d, 1 H, J = 1 Hz, H ₆ o-pyrazine), 9.43 (d, 1 H, J = 8 Hz, NH amide), 10.84 (s, 2H, NH indole and NH Indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-индол), 25.3 (

-СН₂-индол), 27.9 (CH₂ βTrp), 44.1 (СН₂-о,пара-диметоксибензил), 45.5 (CH αTrp), 55.5 (OCH₃), 55.8 (OCH₃), 98.8 (C₃ о,пара-диметоксибензил), 104.9 (C₅ о,пара-диметоксибензил), 109.3 (C₃ Trp), 111.8 (C₇ индол и C₇ Trp), 112.1 (C₃ индол), 113.4 (С₁ о,пара-диметоксибензил), 118.4 (C₄ индол), 118.5 (C₄ Trp), 118.8 (C₅ индол и C₅ Trp), 121.5 (C₆ индол и C₆ Trp), 127.0 (C₉ индол), 127.4 (C₉ Trp), 136.4 (C₈ Trp), 136.6 (C₈ индол), 141.2 (C₆ о-пиразин), 144.1 (C₂ о-пиразин), 144.3 (C₃ о-пиразин), 146.8 (C₅ о-пиразин), 155.4 (Cq триазол), 156.0 (Cq триазол), 157.8 (C₂ о,пара-диметоксибензил), 161.0 (CO амид), 163.2 (C₄ о,пара-диметоксибензил).δ (ppm) 22.0 (CH ₂ -

-indole), 25.3 (

-CH ₂ -indole), 27.9 (CH ₂ βTrp), 44.1 (CH ₂ -o, para-dimethoxybenzyl), 45.5 (CH αTrp), 55.5 (OCH ₃ ), 55.8 (OCH ₃ ), 98.8 (C ₃ о, para-dimethoxybenzyl), 104.9 (C ₅ о, para-dimethoxybenzyl), 109.3 (C ₃ Trp), 111.8 (C ₇ indole and C ₇ Trp), 112.1 (C ₃ indole), 113.4 (C ₁ o, para-dimethoxybenzyl ), 118.4 (C ₄ indole), 118.5 (C ₄ Trp), 118.8 (C ₅ indole and C ₅ Trp), 121.5 (C ₆ indole and C ₆ Trp), 127.0 (C ₉ indole), 127.4 (C ₉ Trp ), 136.4 (C ₈ Trp), 136.6 (C ₈ indole), 141.2 (C ₆ o-pyrazine), 144.1 (C ₂ o-pyrazine), 144.3 (C ₃ o-pyrazine), 146.8 (C ₅ o-pyrazine ), 155.4 (Cq triazole), 156.0 (Cq triazole), 157.8 (C ₂ about, para-dimethoxybenzyl), 161.0 (CO amide), 163.2 (C ₄ about, para-dimethoxybenzyl).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) picolinamide (Compound 73):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-индол), 3.47 (m, 2Н, CH₂ βTrp), 3.57 (s, 3Н, OCH₃), 3.60 (s, 3Н, ОСН₃), 5.05 (m, 2Н, СН₂-о,пара-диметоксибензил), 5.56 (m, 1Н, СН αTrp), 6.14 (dd, 1 Н, J₀=8 Hz и J_m=2 Hz, H₅ о,пара-диметоксибензил), 6.41 (d, 1H, J_m=2 Hz, H₃ о,пара-диметоксибензил), 6.52 (d, 1 Н, J₀=8 Hz, Н₆ о,пара-диметоксибензил), 6.88 (t, 2Н, J₀=7 Hz, H₅ индол и H₅ Trp), 6.99 (t, 1 H, J₀=8 Hz, H₆ Trp), 7.01 (t, 1 H, J₀=8 Hz, H₆ индол), 7.04 (d, 1 H, J=2 Hz, H₂ Trp), 7.07 (d, 1H, J=2 Hz, H₂ индол), 7.27-7.33 (m, 4H, H₄ и H₇ Trp, H₄ и H₇ индол), 7.55 (m, 1 H, NH амид), 7.90 (m, 2H, H₄ и H₅ о-пиридил), 8.57 (d, 1 H, Jαβ=4 Hz, H₆ о-пиридил), 9.15 (d, 1 H, J=8 Hz, H₃ о-пиридил), 10.78 (brs, 2H NH индол и NH индол Trp).δ (ppm) 2.94 (m, 4H,

-

-indole), 3.47 (m, 2H, CH ₂ βTrp), 3.57 (s, 3H, OCH ₃ ), 3.60 (s, 3H, OCH ₃ ), 5.05 (m, 2H, CH ₂ -o, para-dimethoxybenzyl) , 5.56 (m, 1H, СН αTrp), 6.14 (dd, 1 Н, J ₀ = 8 Hz and J _m = 2 Hz, H ₅ о, para-dimethoxybenzyl), 6.41 (d, 1H, J _m = 2 Hz , H ₃ о, para-dimethoxybenzyl), 6.52 (d, 1 Н, J ₀ = 8 Hz, Н ₆ о, para-dimethoxybenzyl), 6.88 (t, 2Н, J ₀ = 7 Hz, H ₅ indole and H ₅ Trp), 6.99 (t, 1 H, J ₀ = 8 Hz, H ₆ Trp), 7.01 (t, 1 H, J ₀ = 8 Hz, H ₆ indole), 7.04 (d, 1 H, J = 2 Hz , H ₂ Trp), 7.07 (d, 1H, J = 2 Hz, H ₂ indole), 7.27-7.33 (m, 4H, H ₄ and H ₇ Trp, H ₄ and H ₇ indole), 7.55 (m, 1 H, NH amide), 7.90 (m, 2H, H ₄ and H ₅ o-pyridyl), 8.57 (d, 1 H, Jαβ = 4 Hz, H ₆ o-pyridyl), 9.15 (d, 1 H, J = 8 Hz, H ₃ o-pyridyl), 10.78 (brs, 2H NH indole and NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-индол), 25.6 (

-СН₂-индол), 28.9 (CH₂ βTrp), 43.1 (СН₂-о,пара-диметоксибензил), 45.5 (СН αTrp), 55.5 (ОСН₃), 55.8 (ОСН₃), 98.9 (С₃ о,пара-диметоксибензил), 105.0 (С₅ о,пара-диметоксибензил), 109.5 (С₃ Trp), 111.8 (С₇ индол и С₇ Trp), 112.8 (С₃ индол), 114.4 (С₁ о,пара-диметоксибензил), 118.4 (С₄ индол и С₄ Trp), 118.7 (С₅ индол), 118.8 (С₅ Trp), 121.4 (С₆ индол и С₆ Trp), 122.5 (С₂ индол и С₃ о-пиридил), 123.1 (С₂ Trp), 127.1 (С₅ о-пиридил), 127.2 (С₉ индол), 127.5 (С₉ Trp), 128.6 (С₆ о,пара-диметоксибензил), 136.4 (С₈ Trp), 136.6 (С₈ индол), 139.1 (С₄ о-пиридил), 146.6 (С₆ о-пиридил), 150.6 (С₂ о-пиридил), 155.5 (Cq триазол), 155.6 (Cq триазол), 157.8 (С₂ о,пара-диметоксибензил), 161.0 (С₄ о,пара-диметоксибензил), 163.9 (СО амид).δ (ppm) 22.3 (CH ₂ -

-indole), 25.6 (

-CH ₂ -indole), 28.9 (CH ₂ βTrp), 43.1 ( С Н ₂ о, para-dimethoxybenzyl), 45.5 (СН αTrp), 55.5 (OCH ₃ ), 55.8 (OCH ₃ ), 98.9 (С ₃ о , para-dimethoxybenzyl), 105.0 (С ₅ о, para-dimethoxybenzyl), 109.5 (С ₃ Trp), 111.8 (С ₇ indole and С ₇ Trp), 112.8 (С ₃ indole), 114.4 (С ₁ о, para- dimethoxybenzyl), 118.4 (C ₄ indole and C ₄ Trp), 118.7 (C ₅ indole), 118.8 (C ₅ Trp), 121.4 (C ₆ indole and C ₆ Trp), 122.5 (C ₂ indole and C ₃ o-pyridyl ), 123.1 (С ₂ Trp), 127.1 (С ₅ о-pyridyl), 127.2 (С ₉ indol), 127.5 (С ₉ Trp), 128.6 (С ₆ о, para-dimethoxybenzyl), 136.4 (С ₈ Trp), 136.6 (C ₈ indole), 139.1 (C ₄ o-pyridyl), 146.6 (C ₆ o-pyridyl), 150.6 (C ₂ o-pyridyl), 155.5 (Cq triazole), 155.6 (Cq triazole), 157.8 (C ₂ o, p-dimethoxybenzyl), 161.0 _(C4 o, p- imetoksibenzil), 163.9 (CO amide).

(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) ethanamine (Compound 74):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-СН₂-индол), 2.86 (m, 2Н, СН₂-

-индол), 3.30 (dd, 1 Н, ³J=14 Hz и 5 Hz,

βTrp), 3.38 (dd, 1H, ³J=14 Hz и 6 Hz,

βTrp), 3.62 (s, 3Н, OCH₃), 3.63 (s, 3Н, ОСН₃), 4.47 (d, 1 Н, ³J=17 Hz, СН₂-о,пара-диметоксибензил), 4.59 (d, 1 Н, ³J=17 Hz, СН₂-о,пара-диметоксибензил), 6.11 (dd, 1 H, J₀=8 Hz и J_m=2 Hz, H₅ о,пара-диметоксибензил), 6.20 (d, 1 H, J₀=8 Hz, H₆ о,пара-диметоксибензил), 6.45 (d, 1 H, J_m=2 Hz, H₃ о,пара-диметоксибензил), 6.87 (t, 1H, J₀=8 Hz, H₅ Trp), 6.91 (t, 1 H, J₀=8 Hz, H₅ индол), 7.00-7.04 (m, 2H, H₆ индол и H₆ Trp), 7.07 (s, 1 H, H₂ индол), 7.09 (s, 1 H, H₂ Trp), 7.17-7.35 (m, 4H, H₄ и H₇ индол, H₄ и H₇ Trp), 8.75 (brs, 3Н, NН₂ ТFА соль), 10.78 (s, 1 H, NH индол), 11.00 (s, 1 H, NH индол Trp).δ (ppm) 2.79 (m, 2H,

-CH ₂ -indole), 2.86 (m, 2H, CH ₂ -

-indole), 3.30 (dd, 1 Н, ³ J = 14 Hz and 5 Hz,

βTrp), 3.38 (dd, 1H, ³ J = 14 Hz and 6 Hz,

βTrp), 3.62 (s, 3H, OCH ₃ ), 3.63 (s, 3H, OCH ₃ ), 4.47 (d, 1 H, ³ J = 17 Hz, CH ₂ -o, para-dimethoxybenzyl), 4.59 (d, 1 H, ³ J = 17 Hz, CH ₂ -o, para-dimethoxybenzyl), 6.11 (dd, 1 H, J ₀ = 8 Hz and J _m = 2 Hz, H ₅ about, para-dimethoxybenzyl), 6.20 (d , 1 H, J ₀ = 8 Hz, H ₆ about, para-dimethoxybenzyl), 6.45 (d, 1 H, J _m = 2 Hz, H ₃ about, para-dimethoxybenzyl), 6.87 (t, 1H, J ₀ = 8 Hz, H ₅ Trp), 6.91 (t, 1 H, J ₀ = 8 Hz, H ₅ indole), 7.00-7.04 (m, 2H, H ₆ indole and H ₆ Trp), 7.07 (s, 1 H, H ₂ indole), 7.09 (s, 1 H, H ₂ Trp), 7.17-7.35 (m, 4H, H ₄ and H ₇ indole, H ₄ and H ₇ Trp), 8.75 (brs, 3H, NH ₂ TFA salt ), 10.78 (s, 1 H, NH indole), 11.00 (s, 1 H, NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-индол), 25.7 (

-СН₂-индол), 29.9 (

βTrp), 41.5 (

-о,пара-диметоксибензил), 46.5 (CH αTrp), 55.6 (OCH₃), 55.9 (OCH₃), 98.8 (C₃ о,пара-диметоксибензил), 105.0 (C₅ о,пара-диметоксибензил), 107.4 (C₃ Trp), 111.8 (C₇ индол и C₇ Trp), 113.4 (C₃ индол), 115.1 (С₁ о,пара-диметоксибензил), 118.0 (C₄ индол), 118.4 (C₄ Trp), 118.6 (C₅ Trp), 119.0 (C₅ индол), 121.3 (C₆Trp), 121.6 (C₆ индол), 122.9 (C₂ индол), 125.4 (C₂ Trp), 127.1 (C₉ индол и C₉ Trp), 128.5 (C₆ о,пара-диметоксибензил), 136.5 (C₈ Trp), 136.6 (C₈ индол), 152.3 (Cq триазол), 155.6 (Cq триазол), 157.6 (C₂ о,пара-диметоксибензил), 160.8 (C₄ о,пара-диметоксибензил).δ (ppm) 22.9 (CH ₂ -

-indole), 25.7 (

-CH ₂ -indole), 29.9 (

βTrp), 41.5 (

-o, para-dimethoxybenzyl), 46.5 (CH αTrp), 55.6 (OCH ₃ ), 55.9 (OCH ₃ ), 98.8 (C ₃ о, para-dimethoxybenzyl), 105.0 (C ₅ о, para-dimethoxybenzyl), 107.4 ( C ₃ Trp), 111.8 (C ₇ indole and C ₇ Trp), 113.4 (C ₃ indole), 115.1 (C ₁ о, para-dimethoxybenzyl), 118.0 (C ₄ indole), 118.4 (C ₄ Trp), 118.6 ( C ₅ Trp), 119.0 (C ₅ indole), 121.3 (C ₆ Trp), 121.6 (C ₆ indole), 122.9 (C ₂ indole), 125.4 (C ₂ Trp), 127.1 (C ₉ indole and C ₉ Trp) , 128.5 (C ₆ about, para-dimethoxybenzyl), 136.5 (C ₈ Trp), 136.6 (C ₈ indole), 152.3 (Cq triazole), 155.6 (Cq triazole), 157.6 (C ₂ about, para-dimethoxybenzyl), 160.8 (C ₄ about, para-dimethoxybenzyl).

(R) -H- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide (Compound 79):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-фенил), 3.51 (m, 2Н, СН₂ βTrp), 3.59 (s, 3Н, ОСН₃), 5.11 (d, 1 Н, J=17 Hz, СН₂-пара-метоксибензил), 5.23 (d, 1Н, J=17 Hz, СН₂-пара-метоксибензил), 5.51 (m, 1 Н, CH αTrp), 6.59 (d, 2H, J₀=8 Hz, H₃ и H₅ пара-метоксибензил), 6.73 (d, 2H, J₀=8 Hz, H₂ и H₆ пара-метоксибензил), 6.87 (t, 1 H, J₀=8 Hz, H₅ Trp), 7.01 (t, 1 H, J₀=8 Hz, H₆ Trp), 7.06 (m, 2H, H₂ и H₆ фенил), 7.10 (d, 1 H, J=2 Hz, H₂ Trp), 7.14 (d, 1 H, J₀=7 Hz, H₄ Trp), 7.24 (m, 3Н, H₃, H₄ и H₅ фенил), 7.34 (d, 1 H, J₀=8 Hz, H₇ Trp), 7.55 (m, 1 H, NH амид), 7.88 (m, 2H, H₄ и H₅ о-пиридил), 8.56 (d, 1 H, Jαβ=4 Hz, H₆ о-пиридил), 9.20 (d, 1 H, J₀=8 Hz, H₃ о-пиридил), 10.80 (s, 1H, NH индол Trp).δ (ppm) 2.85 (m, 4H,

-

phenyl), 3.51 (m, 2H, CH ₂ βTrp), 3.59 (s, 3H, OCH ₃ ), 5.11 (d, 1 H, J = 17 Hz, CH ₂ -paramethoxybenzyl), 5.23 (d, 1H , J = 17 Hz, CH ₂ -para-methoxybenzyl), 5.51 (m, 1 H, CH αTrp), 6.59 (d, 2H, J ₀ = 8 Hz, H ₃ and H ₅ para-methoxybenzyl), 6.73 (d , 2H, J ₀ = 8 Hz, H ₂ and H ₆ para-methoxybenzyl), 6.87 (t, 1 H, J ₀ = 8 Hz, H ₅ Trp), 7.01 (t, 1 H, J ₀ = 8 Hz, H ₆ Trp), 7.06 (m, 2H, H ₂ and H ₆ phenyl), 7.10 (d, 1 H, J = 2 Hz, H ₂ Trp), 7.14 (d, 1 H, J ₀ = 7 Hz, H ₄ Trp), 7.24 (m, 3H, H ₃ , H ₄ and H ₅ phenyl), 7.34 (d, 1 H, J ₀ = 8 Hz, H ₇ Trp), 7.55 (m, 1 H, NH amide), 7.88 (m, 2H, H ₄ and H ₅ o-pyridyl), 8.56 (d, 1 H, Jαβ = 4 Hz, H ₆ o-pyridyl), 9.20 (d, 1 H, J ₀ = 8 Hz, H ₃ o-pyridyl), 10.80 (s, 1H, NH indol Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-СН₂-фенил), 28.6 (CH₂ βTrp), 32.1 (СН₂-

-фенил), 45.5 (CH αTrp), 46.2 (

-пара-метоксибензил), 55.4 (OCH₃), 109.6 (C₃ Trp), 111.8 (C₇ Trp), 114.3 (С₃ и С₅ пара-метоксибензил), 118.5 (C₄ Trp), 118.8 (C₅ Trp), 121.4 (C₆ Trp), 122.5 (C₃ о-пиридил), 124.5 (C₂ Trp), 127.2 (C₂ и С₆ фенил), 127.4 (C₉ Trp и С₁ пара-метоксибензил), 127.8 (C₅ о-пиридил), 128.7 (C₂ и C₆ пара-метоксибензил), 128.8 (C₃, C₄ и C₅ фенил), 136.4 (C₈ Trp), 138.1 (C₄ о-пиридил), 140.3 (С₁ фенил), 148.7 (C₆ о-пиридил), 149.3 (C₂ о-пиридил), 155.0 (Cq триазол), 155.3 (Cq триазол), 159.0 (C₄ пара-метоксибензил), 164.1 (CO амид).δ (ppm) 26.2 (

-CH ₂ -phenyl), 28.6 (CH ₂ βTrp), 32.1 (CH ₂ -

phenyl), 45.5 (CH αTrp), 46.2 (

-para-methoxybenzyl), 55.4 (OCH ₃ ), 109.6 (C ₃ Trp), 111.8 (C ₇ Trp), 114.3 (C ₃ and C ₅ para-methoxybenzyl), 118.5 (C ₄ Trp), 118.8 (C ₅ Trp ), 121.4 (C ₆ Trp), 122.5 (C ₃ o-pyridyl), 124.5 (C ₂ Trp), 127.2 (C ₂ and C ₆ phenyl), 127.4 (C ₉ Trp and C ₁ para-methoxybenzyl), 127.8 ( C ₅ o-pyridyl), 128.7 (C ₂ and C ₆ para-methoxybenzyl), 128.8 (C ₃ , C ₄ and C ₅ phenyl), 136.4 (C ₈ Trp), 138.1 (C ₄ o-pyridyl), 140.3 ( C ₁ phenyl), 148.7 (C ₆ o-pyridyl), 149.3 (C ₂ o-pyridyl), 155.0 (Cq triazole), 155.3 (Cq triazole), 159.0 (C ₄ para-methoxybenzyl), 164.1 (CO amide).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) picolinamide (Compound 80):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-индол), 3.48 (m, 2Н, CH₂ βTrp), 3.58 (s, 3Н, ОСН₃), 5.16 (m, 2Н, СН₂-пара-метоксибензил), 5.50 (m, 1 Н, CH αTrp), 6.57 (d, 2Н, J₀=8 Hz, Н₃ и Н₅ пара-метоксибензил), 6.72 (d, 2Н, J₀=8 Hz, Н₂ и Н₆ пара-метоксибензил), 6.87 (t, 2Н, J₀=8 Hz, Н₅ Trp и Н₅ индол), 6.96-7.07 (m, 5Н, Н₂ и Н₆ индол, Н₂, Н₄ и Н₆ Trp), 7.27-7.34 (m, 3Н, Н₄ и Н₇ индол, Н₇ Trp), 7.55 (m, 1 Н, NH амид), 7.88 (m, 2Н, Н₄ и Н₅ о-пиридил), 8.56 (d, 1 Н, Jαβ=4 Hz, Н₆ о-пиридил), 9.18 (d, 1 Н, J₀=8 Hz, Н₃ о-пиридил), 10.77 (brs, 2Н, NH индол Trp и NH индол).δ (ppm) 2.95 (m, 4H,

-

-indole), 3.48 (m, 2H, CH ₂ βTrp), 3.58 (s, 3H, OCH ₃ ), 5.16 (m, 2H, CH ₂ -paramethoxybenzyl), 5.50 (m, 1 H, CH αTrp), 6.57 (d, 2H, J ₀ = 8 Hz, H ₃ and H ₅ para-methoxybenzyl), 6.72 (d, 2H, J ₀ = 8 Hz, H ₂ and H ₆ para-methoxybenzyl), 6.87 (t, 2H, J ₀ = 8 Hz, H ₅ Trp and H ₅ indole), 6.96-7.07 (m, 5H, H ₂ and H ₆ indole, H ₂ , H ₄ and H ₆ Trp), 7.27-7.34 (m, 3H, H ₄ and H ₇ indole, H ₇ Trp), 7.55 (m, 1 H, NH amide), 7.88 (m, 2H, H ₄ and H ₅ o-pyridyl), 8.56 (d, 1 H, Jαβ = 4 Hz, H ₆ o-pyridyl), 9.18 (d, 1 H, J ₀ = 8 Hz, H ₃ o-pyridyl), 10.77 (brs, 2H, NH indole Trp and NH indole).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-индол), 25.7 (

-СН₂-индол), 28.9 (CH₂ βTrp), 45.5 (СН αTrp), 46.2 (

-пара-метоксибензил), 55.4 (ОСН₃), 109.7 (С₃ Trp), 111.8 (С₇ Trp и С₇ индол), 112.6 (С₃ индол), 114.3 (С₃ и С₅ пара-метоксибензил), 118.4 (С₄ Trp и С₄ индол), 118.7 (С₅ индол), 118.8 (С₅ Trp), 121.4 (С₆ Trp и С₆ индол), 122.4 (С₃ О-пиридил и С₂ индол), 124.5 (С₂ Trp), 126.7 (С₉ индол), 127.1 (С₉ Trp), 127.2 (С₅ о-пиридил), 127.5 (С₁ пара-метоксибензил), 127.7 (С₂ и С₆ пара-метоксибензил), 136.4 (С₈ Trp), 136.6 (С₈ индол), 138.1 (С₄ о-пиридил), 148.7 (С₆ о-пиридил), 149.3 (С₂ о-пиридил), 155.3 (Cq триазол), 159.0 (С₄ пара-метоксибензил), 164.0 (СО амид).δ (ppm) 22.4 (CH ₂ -

-indole), 25.7 (

-CH ₂ -indole), 28.9 (CH ₂ βTrp), 45.5 (СН αTrp), 46.2 (

-para-methoxybenzyl), 55.4 (OCH ₃ ), 109.7 (C ₃ Trp), 111.8 (C ₇ Trp and C ₇ indole), 112.6 (C ₃ indole), 114.3 (C ₃ and C ₅ para-methoxybenzyl), 118.4 (C ₄ Trp and C ₄ indole), 118.7 (C ₅ Trp), 118.8 (C ₅ Trp), 121.4 (C ₆ Trp and C ₆ indol), 122.4 (C ₃ O-pyridyl and C ₂ indole), 124.5 ( _C2 Trp), 126.7 _(C9 indole), 127.1 _(C9 Trp), 127.2 _(C5 o-pyridyl), 127.5 _(C1 p-methoxybenzyl), 127.7 _(C2 and _C6 p-methoxybenzyl), 136.4 (C ₈ Trp), 136.6 (C ₈ indole), 138.1 (C ₄ o-pyridyl), 148.7 (C ₆ o-pyridyl), 149.3 (C ₂ o-pyridyl), 155.3 (Cq triazole), 159.0 (C ₄ para-methoxybenzyl), 164.0 (СО amide).

(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) ethyl) piperazine-2-carboxamide (Compound 81):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-индол), 3.61 (s, 3Н, ОМе), 3.64 (m, 1Н, Н₃ пиперазин), 4.82 (m, 2Н, СН₂-пара-метоксибензил), 5.40 (m, 1 Н, СН αTrp), 6.45 (d, 2Н, J₀=8 Hz, Н₃ и Н₅ пара-метоксибензил), 6.51 (d, 2Н, J₀=8 Hz, Н₂ и Н₆ пара-метоксибензил), 6.65-7.47 (m, 1OH, СНаr, индол и индол Trp), 8.95 (m, 1 Н, NH амид), 10.88 (d, 1Н, J=2 Hz, NH индол), 10.91 (s, 1 Н, NH индол Trp).δ (ppm) 2.18 (m, 2H, NH piperazine), 2.96 (m, 6H, H ₂ , H ₅ and H ₆ piperazine), 3.34 (d, 2H, J = 7 Hz, CH ₂ βTrp), 3.57 (m , 4H,

-

-indole), 3.61 (s, 3Н, OMe), 3.64 (m, 1Н, Н ₃ piperazine), 4.82 (m, 2Н, СН ₂ -para-methoxybenzyl), 5.40 (m, 1 Н, СН αTrp), 6.45 (d, 2H, J ₀ = 8 Hz, H ₃ and H ₅ para-methoxybenzyl), 6.51 (d, 2H, J ₀ = 8 Hz, H ₂ and H ₆ para-methoxybenzyl), 6.65-7.47 (m, 1OH , CHаr, indole and indole Trp), 8.95 (m, 1 Н, NH amide), 10.88 (d, 1Н, J = 2 Hz, NH indole), 10.91 (s, 1 Н, NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-индол), 25.6 (

-СН₂-индол), 31.3 (CH₂ βTrp), 41.9 (СН₂-пара-метоксибензил), 47.7 (CH αTrp, C₅ и C₆ пиперазин), 55.5 (OCH₃ и С₂ пиперазин), 61.1 (С₃ пиперазин), 109.3 (С₃Trp), 111.7 (С₇ индол и С₇ Trp), 114.0 (С₃ индол), 114.3 (С₃ и С₅ пара-метоксибензил), 118.6 (С₄ индол), 118.7 (С₄Trp), 118.9 (С₅ индол и С₅ Trp), 121.4 (С₆ индол), 121.5 (С₆ Trp), 123.9 (С₂ индол и С₂ Trp), 127.0 (С₉ индол), 127.2 (С₉ Trp), 127.7 (С₁ пара-метоксибензил), 128.1 (С₂ и С₆ пара-метоксибензил), 136.3 (С₈ Trp), 136.5 (С₈ индол), 155.5 (Cq триазол), 162.2 (С₄ пара-метоксибензил), 171.1 (СО амид).δ (ppm) 22.5 (CH ₂ -

-indole), 25.6 (

-CH ₂ -indole), 31.3 (CH ₂ βTrp), 41.9 (CH ₂ -para-methoxybenzyl), 47.7 (CH αTrp, C ₅ and C ₆ piperazine), 55.5 (OCH ₃ and C ₂ piperazine), 61.1 (C ₃ piperazine), 109.3 (C ₃ Trp), 111.7 (C ₇ indole and C ₇ Trp), 114.0 (C ₃ indole), 114.3 (C ₃ and C ₅ para-methoxybenzyl), 118.6 (C ₄ indole), 118.7 ( C ₄ Trp), 118.9 (C ₅ indole and C ₅ Trp), 121.4 (C ₆ indole), 121.5 (C ₆ Trp), 123.9 (C ₂ indole and C ₂ Trp), 127.0 (C ₉ indole), 127.2 ( C ₉ Trp), 127.7 (C ₁ para-methoxybenzyl), 128.1 (C ₂ and C ₆ para-methoxybenzyl), 136.3 (C ₈ Trp), 136.5 (C ₈ indole), 155.5 (Cq triazole), 162.2 (C ₄ para-methoxybenzyl), 171.1 (СО amide).

(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide (Compound 89):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-индол), 3.05 (t, 2Н, J=6 Hz, H₅ Pro), 3.30 (m, 2H, CH₂ βTrp), 3.67 (s, 3H, OCH₃), 3.96 (m, 1 H, CH αPro), 5.02 (s, 2H, СН₂-пара-метоксибензил), 5.19 (m, 1 H, СН αTrp), 6.73 (s, 4H, CHar пара-метоксибензил), 6.84 (t, 1 H, J₀=8 Hz, H₅ индол), 6.90 (t, 1 H, J₀=8 Hz, H₅ Trp), 6.93-7.06 (m, 4H, H₂ и H₆ индол, H₂ и H₆ Trp), 7.17 (d, 1 H, J₀=8 Hz, H₄ Trp), 7.29 (d, 3H, J₀=8 Hz, H₄ и H₇ индол, H₇ Trp), 8.39 и 9.10 (2 m, 2H, NH Pro TFA соль), 9.25 (d, 1H, J=8 Hz, NH амид), 10.76 (s, 1 H, NH индол), 10.80 (d, 1 H, J=2 Hz, NH индол Trp).δ (ppm) 1.42 (m, 1 H, H ₃ Pro), 1.52 (m, 1H, H ₄ Pro), 1.72 (m, 1H, H ₄ Pro), 2.07 (m, 1 H, H ₃ Pro), 2.94 (m, 4H,

-

-indole), 3.05 (t, 2H, J = 6 Hz, H ₅ Pro), 3.30 (m, 2H, CH ₂ βTrp), 3.67 (s, 3H, OCH ₃ ), 3.96 (m, 1 H, CH αPro ), 5.02 (s, 2H, CH ₂ -para-methoxybenzyl), 5.19 (m, 1 H, CH αTrp), 6.73 (s, 4H, CHar para-methoxybenzyl), 6.84 (t, 1 H, J ₀ = 8 Hz, H ₅ indole), 6.90 (t, 1 H, J ₀ = 8 Hz, H ₅ Trp), 6.93-7.06 (m, 4H, H ₂ and H ₆ indole, H ₂ and H ₆ Trp), 7.17 ( d, 1 H, J ₀ = 8 Hz, H ₄ Trp), 7.29 (d, 3H, J ₀ = 8 Hz, H ₄ and H ₇ indole, H ₇ Trp), 8.39 and 9.10 (2 m, 2H, NH Pro TFA salt), 9.25 (d, 1H, J = 8 Hz, NH amide), 10.76 (s, 1 H, NH indole), 10.80 (d, 1 H, J = 2 Hz, NH indol Trp).

¹³ C NMR (75 MHz1 DMSO d ⁶ , 300 K):

-индол), 23.5 (C₄ Pro), 25.8 (

-СН₂-индол), 29.4 (CH₂ βTrp), 29.8 (C₃ Pro), 45.2 (CH αTrp), 45.5 (СН₂-пара-метоксибензил), 46.0 (C₅ Pro), 55.5 (OCH₃), 59.3 (CH αPro), 109.6 (C₃ Trp), 111.8 (C₇ индол и C₇ Trp), 113.4 (C₃ индол), 114.6 (C₃ и C₅ пара-метоксибензил), 118.4 (C₄ индол), 118.5 (C₄ Trp), 118.7 (C₅ индол и C₅ Trp), 121.4 (C₆ индол и C₆ Trp), 123.0 (C₂ Trp), 124.7 (C₂ индол), 127.2 (С₉ индол), 127.3 (C₉ Trp), 127.7 (C₁ пара-метоксибензил), 127.8 (C₂ и C₆ пара-метоксибензил), 126.5 (C₈ Trp), 136.6 (C₈ индол), 154.8 (Cq триазол), 154.9 (Cq триазол), 159.2 (C₄ пара-метоксибензил), 168.2 (CO амид).δ (ppm) 22.8 (CH ₂ -

-indole), 23.5 (C ₄ Pro), 25.8 (

-CH ₂ -indole), 29.4 (CH ₂ βTrp), 29.8 (C ₃ Pro), 45.2 (CH αTrp), 45.5 (CH ₂ -paramethoxybenzyl), 46.0 (C ₅ Pro), 55.5 (OCH ₃ ), 59.3 (CH αPro), 109.6 (C ₃ Trp), 111.8 (C ₇ indole and C ₇ Trp), 113.4 (C ₃ indole), 114.6 (C ₃ and C ₅ para-methoxybenzyl), 118.4 (C ₄ indole), 118.5 (C ₄ Trp), 118.7 (C ₅ indole and C ₅ Trp), 121.4 (C ₆ indole and C ₆ Trp), 123.0 (C ₂ Trp), 124.7 (C ₂ indole), 127.2 (C ₉ indole), 127.3 (C ₉ Trp), 127.7 (C ₁ para-methoxybenzyl), 127.8 (C ₂ and C ₆ para-methoxybenzyl), 126.5 (C ₈ Trp), 136.6 (C ₈ indole), 154.8 (Cq triazole), 154.9 ( Cq triazole), 159.2 (C ₄ para-methoxybenzyl), 168.2 (CO amide).

(R) -H - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide (Compound 90):

¹ N NMR (300 MHz, DMSO d ⁶ , 300K):

-

-индол), 3.31 (dd, 1 Н, J=14 Hz и 7 Hz, CH₂ βTrp), 3.41 (dd, 1 H, J=14 Hz и 8 Hz, CH₂ βTrp), 3.63 (s, 3Н, OCH₃), 4.05 (m, 1H, CH αPro), 4.86 (s, 2H, СН₂-пара-метоксибензил), 5.21 (m, 1H, CHαTrp), 6.63 (s, 4H, СНаr пара-метоксибензил), 6.88 (t, 2H, J₀=7 Hz, H₅ индол и H₅ Trp), 7.02 (m, 4H, H₂ и H₆ индол, H₂ и H₆ Trp), 7.26-7.34 (m, 4H, H₄ и H₇ индол, H₄ и H₇ Trp), 8.51 и 9.18 (2 m, 2H, NH Pro, ТFА соль), 9.27 (d, 1 H, J=8 Hz, NH амид), 10.73 (s, 1H, NH индол), 10.80 (s, 1 H, NH индол Trp).δ (ppm) 1.23 (m, 1H, H ₃ Pro), 1.52 (m, 1 H, H ₄ Pro), 1.74 (m, 1 H, H ₄ Pro), 2.08 (m, 1 H, H ₃ Pro) , 2.81 (m, 2H, H ₅ Pro), 2.90-3.14 (m, 4H,

-

-indole), 3.31 (dd, 1 H, J = 14 Hz and 7 Hz, CH ₂ βTrp), 3.41 (dd, 1 H, J = 14 Hz and 8 Hz, CH ₂ βTrp), 3.63 (s, 3Н, OCH ₃ ), 4.05 (m, 1H, CH αPro), 4.86 (s, 2H, CH ₂ -para-methoxybenzyl), 5.21 (m, 1H, CHαTrp), 6.63 (s, 4H, CH-para-methoxybenzyl), 6.88 (t, 2H, J ₀ = 7 Hz, H ₅ indole and H ₅ Trp), 7.02 (m, 4H, H ₂ and H ₆ indole, H ₂ and H ₆ Trp), 7.26-7.34 (m, 4H, H ₄ and H ₇ indole, H ₄ and H ₇ Trp), 8.51 and 9.18 (2 m, 2H, NH Pro, TFA salt), 9.27 (d, 1 H, J = 8 Hz, NH amide), 10.73 (s, 1H, NH indole), 10.80 (s, 1H, NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-индол), 23.8 (C₄ Pro), 25.9 (

-СН₂-индол), 29.7 (CH₂ βTrp и C₃ Pro), 45.4 (СН₂-пара-метоксибензил), 45.8 (СН αTrp), 46.1 (C₅ Pro), 55.5 (OCH₃), 59.2 (CH αPro), 109.7 (C₃ Trp), 111.8 (C₇ Trp), 111.9 (C₇ индол), 113.4 (C₃ индол), 114.4 (C₃ и C₅ пара-метоксибензил), 118.3 (C₄ индол), 118.5 (C₄ Trp), 118.6 (C₅ индол), 118.9 (C₅ Trp), 121.4 (C₆ индол и C₆ Trp), 122.9 (C₂ индол и C₂ Trp), 127.2 (C₉ индол), 127.4 (C₉ Trp), 127.6 (C₁, C₂ и C₆ пара-метоксибензил), 136.5 (C₈ Trp), 136.6 (C₈ индол), 154.4 (Cq триазол), 155.0 (Cq thazole), 159.1 (C₄ пара-метоксибензил), 168.3 (CO амид).δ (ppm) 22.8 (CH ₂ -

-indole), 23.8 (C ₄ Pro), 25.9 (

-CH ₂ -indole), 29.7 (CH ₂ βTrp and C ₃ Pro), 45.4 (CH ₂ -para-methoxybenzyl), 45.8 (CH αTrp), 46.1 (C ₅ Pro), 55.5 (OCH ₃ ), 59.2 (CH αPro), 109.7 (C ₃ Trp), 111.8 (C ₇ Trp), 111.9 (C ₇ indole), 113.4 (C ₃ indole), 114.4 (C ₃ and C ₅ para-methoxybenzyl), 118.3 (C ₄ indole), 118.5 (C ₄ Trp), 118.6 (C ₅ Indole), 118.9 (C ₅ Trp), 121.4 (C ₆ indole and C ₆ Trp), 122.9 (C ₂ indole and C ₂ Trp), 127.2 (C ₉ indole), 127.4 (C ₉ Trp), 127.6 (C ₁ , C ₂ and C ₆ para-methoxybenzyl), 136.5 (C ₈ Trp), 136.6 (C ₈ indole), 154.4 (Cq triazole), 155.0 (Cq thazole), 159.1 ( C ₄ para-methoxybenzyl), 168.3 (CO amide).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-bromobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 92):

¹ N NMR (400 MHz, DMSO-d ⁶ ):

-СН₂-индол), 3.00 (2H, m, СН₂-

-индол), 3.37 (2Н, m, СН₂ βTrp), 5.10 (2Н, s, СН₂ 4-бромобензил), 5.13 (1 Н, m, СαН Trp), 6.75 (2Н, d, J=8.1, Н₂, Н₆ 4-бромобензил), 6.88 (1Н, 1, J=7.3, Н₅ Trp), 6.93 (1 Н, t, J=7.5, Н₅ индол), 7.03 (1 Н, t, J=7.0, Н₆ Trp), 7.05 (1 H, Н₆ индол), 7.07 (1 Н, d, J=1.7, Н₂ индол), 7.09 (1 Н, d, J=1.8, Н₂ Trp), 7.12 (1 Н, d, J=8.2, Н₄ Trp), 7.28 (1 Н, d, J=7.9, H₄ индол), 7.32 (2Н, d, J=8.2, H₇ Trp, H₇ индол), 7.41 (2Н, d, J=8.1, Н₃, Н₅ 4-бромобензил), 8.01 (2Н, s, NH₂ Aib), 8.95 (1 Н, d, J=7.9, NH Trp), 10.77 (1 H, brs, NH индол), 10.80 (1H, brs, NH индол Trp).δ (ppm) 1.28 (3H, s, CH ₃ Aib), 1.30 (3H, s, CH ₃ Aib), 2.90 (2H, m,

-CH ₂ -indole), 3.00 (2H, m, CH ₂ -

-indole), 3.37 (2Н, m, СН ₂ βTrp), 5.10 (2Н, s, СН ₂ 4-bromobenzyl), 5.13 (1 Н, m, СαН Trp), 6.75 (2Н, d, J = 8.1, Н ₂ , H ₆ 4-bromobenzyl), 6.88 (1H, 1, J = 7.3, H ₅ Trp), 6.93 (1 H, t, J = 7.5, H ₅ indole), 7.03 (1 H, t, J = 7.0 , H ₆ Trp), 7.05 (1 H, H ₆ indole), 7.07 (1 H, d, J = 1.7, H ₂ indole), 7.09 (1 H, d, J = 1.8, H ₂ Trp), 7.12 ( 1 H, d, J = 8.2, H ₄ Trp), 7.28 (1 H, d, J = 7.9, H ₄ indole), 7.32 (2H, d, J = 8.2, H ₇ Trp, H ₇ indole), 7.41 (2H, d, J = 8.1, H ₃ , H ₅ 4-bromobenzyl), 8.01 (2H, s, NH ₂ Aib), 8.95 (1 H, d, J = 7.9, NH Trp), 10.77 (1 H, brs, NH indole), 10.80 (1H, brs, NH indole Trp).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

-индол), 23.1 (CH₃ Aib), 23.4 (CH₃ Aib), 25.4 (

-СН₂-индол), 28.7 (Cβ Trp), 44.8 (

4-бромобензил), 45.2 (Cα Trp,), 56.3 (Cq Aib), 109.4 (C₃ Trp), 111.3 (C₇ Trp, C₇ индол), 113.0 (C₃ индол), 117.8 (C₄ Trp), 118.0 (C₄ индол), 118.2 (C₅ индол), 118.3 (C₅ Trp), 120.8 (C₄ 4-бромобензил), 120.9 (C₆ Trp, C₆ индол), 122.5 (C₂ индол), 124.4 (C₂ Trp), 126.7 (C₉ индол), 126.8 (C₉ Trp), 128.0 (C₂, C₆ 4-бромобензил), 131.6 (C₃, C₅ 4-бромобензил), 135.1 (С₁ 4-бромобензил), 136.1 (C₈ Trp, C₈ индол), 154.2 (Cq триазол), 154.5 (Cq триазол), 171.4 (CO Aib).δ (ppm) 22.4 (CH ₂ -

-indole), 23.1 (CH ₃ Aib), 23.4 (CH ₃ Aib), 25.4 (

-CH ₂ -indole), 28.7 (Cβ Trp), 44.8 (

4-bromobenzyl), 45.2 (Cα Trp,), 56.3 (Cq Aib), 109.4 (C ₃ Trp), 111.3 (C ₇ Trp, C ₇ indole), 113.0 (C ₃ indole), 117.8 (C ₄ Trp), 118.0 (C ₄ indole), 118.2 (C ₅ indole), 118.3 (C ₅ Trp), 120.8 (C ₄ 4-bromobenzyl), 120.9 (C ₆ Trp, C ₆ indole), 122.5 (C ₂ indole), 124.4 ( C ₂ Trp), 126.7 (C ₉ indole), 126.8 (C ₉ Trp), 128.0 (C ₂ , C ₆ 4-bromobenzyl), 131.6 (C ₃ , C ₅ 4-bromobenzyl), 135.1 (C ₁ 4-bromobenzyl ), 136.1 (C ₈ Trp, C ₈ indole), 154.2 (Cq triazole), 154.5 (Cq triazole), 171.4 (CO Aib).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2-phenylethyl) -2-amino-2-methylpropanamide (Compound 93):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-индол), 3.19 (2Н, m, СН₂ βPhe), 3.69 (3Н, s, ОСН₃), 5.05 (2Н, m, СН₂-пара-метоксибензил), 5.20 (1 Н, m, CH αPhe), 6.82 (2Н, d, J₀=8 Hz, Н₃ и Н₅ пара-метоксибензил), 6.88 (2Н, d, J₀=8 Hz, Н₂ и Н₆ пара-метоксибензил), 6.92 (1 Н, t, J₀=8 Hz, Н₅ индол), 7.02 (1 Н, t, J₀=7 Hz, Н₆ индол), 7.03 (1 Н, d, J=2 Hz, Н₂ индол), 7.11-7.20 (5Н, m, СНаr Phe), 7.29 (2Н, d, J₀=8 Hz, Н₄ и Н₇ индол), 7.99 (3Н, brs, NH₂ Aib), 8.93 (1 Н, d, J=8 Hz, NH амид), 10.77 (1 H, s, NH индол).δ (ppm) 1.18 (3H, s, CH ₃ Aib), 1.27 (3H, s, CH ₃ Aib), 2.91 (4H, m,

-

-indole), 3.19 (2H, m, CH ₂ βPhe), 3.69 (3H, s, OCH ₃ ), 5.05 (2H, m, CH ₂ -para-methoxybenzyl), 5.20 (1 H, m, CH αPhe), 6.82 (2H, d, J ₀ = 8 Hz, H ₃ and H ₅ para-methoxybenzyl), 6.88 (2H, d, J ₀ = 8 Hz, H ₂ and H ₆ para-methoxybenzyl), 6.92 (1 H, t , J ₀ = 8 Hz, H ₅ indole), 7.02 (1 H, t, J ₀ = 7 Hz, H ₆ indole), 7.03 (1 H, d, J = 2 Hz, H ₂ indole), 7.11-7.20 (5H, m, CHаr Phe), 7.29 (2Н, d, J ₀ = 8 Hz, Н ₄ and Н ₇ indole), 7.99 (3Н, brs, NH ₂ Aib), 8.93 (1 Н, d, J = 8 Hz, NH amide), 10.77 (1 H, s, NH indole).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 ° K):

-индол), 23.5 (CH₃ Aib), 23.9 (CH₃ Aib), 25.9 (

-СН₂-индол), 38.7 (СН₂ βPhe), 45.7 (СН₂-пара-метоксибензил), 46.4 (CH αPhe), 55.6 (OCH₃), 56.8 (Cq Aib), 111.8 (C₇ индол), 113.4 (C₃ индол), 114.7 (C₃ и C₅ пара-метоксибензил), 118.5 (C₄ Trp), 118.6 (C₅ Trp), 121.4 (C₆ Trp), 123.0 (C₂ Trp), 127.0 (C₄ фенил), 127.2 (C₉ индол), 127.9 (С₁ пара-метоксибензил), 128.1 (С₂ и С₆ фенил), 128.5 (С₃ и С₅ фенил), 129.8 (С₂ и С₆ пара-метоксибензил), 136.6 (С₈ индол), 137.7 (С₁ фенил), 155.2 (Cq триазол), 154.4 (Cq триазол), 159.3 (С₄ пара-метоксибензил), 171.7 (СО Aib).δ (ppm) 22.8 (CH ₂ -

-indole), 23.5 (CH ₃ Aib), 23.9 (CH ₃ Aib), 25.9 (

-CH ₂ -indole), 38.7 (CH ₂ βPhe), 45.7 (CH ₂ -para-methoxybenzyl), 46.4 (CH αPhe), 55.6 (OCH ₃ ), 56.8 (Cq Aib), 111.8 (C ₇ indole), 113.4 (C ₃ indole), 114.7 (C ₃ and C ₅ para-methoxybenzyl), 118.5 (C ₄ Trp), 118.6 (C ₅ Trp), 121.4 (C ₆ Trp), 123.0 (C ₂ Trp), 127.0 (C ₄ phenyl), 127.2 (C ₉ indole), 127.9 (C ₁ para-methoxybenzyl), 128.1 (C ₂ and C ₆ phenyl), 128.5 (C ₃ and C ₅ phenyl), 129.8 (C ₂ and C ₆ para-methoxybenzyl) 136.6 (C ₈ indole), 137.7 (C ₁ phenyl), 155.2 (Cq triazole), 154.4 (Cq triazole), 159.3 (C ₄ para-methoxybenzyl), 171.7 (CO Aib).

(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide (Compound 95):

¹ N NMR (400 MHz, DMSO-d ⁶ ):

-ln), 2.89 (1Н, m, 1 Н, -N-CH₂-

-ln), 3.28 (1 Н, dd, J=14.2, J=6.8, 1 H CH₂ βTrp), 3.40 (1 H, dd, J=14.2, J=8.4, 1 H CH₂ βTrp), 4.10 (2H, m -N-

-CH₂-ln), 5.25 (1H, m, CHα Trp), 6.85 (1 H, d, J=2.0, H₂ индол), 6.90-6.98 (2H, m, H₅ индол), 7.01 (1 H, d, J=2.0, H₂ индол), 7.02-7.12 (2H, m, H₆ индол), 7.30 (1 H, d, J=8.2, H₇ индол), 7.33 (1 H, d, J=8.3, H₇ индол), 7.40 (1 H, d, J=7.9, H₄ индол), 7.47 (1H, d, J=7.8, H₄ индол), 8.04 (2H, brs, NH₂ Aib), 8.42 (1 H, s, H триазол), 9.01 (1 H, d, J=8.0, NH Trp), 10.81 (1 H, s, NH индол), 10.90 (1 H, s, NH индол).δ (ppm) 1.29 (3H, s, CH ₃ Aib), 1.35 (3H, s, CH ₃ Aib), 2.85 (1 N, m, 1 N N-CH ₂ -

-ln), 2.89 (1H, m, 1H, -N-CH ₂ -

-ln), 3.28 (1 H, dd, J = 14.2, J = 6.8, 1 H CH ₂ βTrp), 3.40 (1 H, dd, J = 14.2, J = 8.4, 1 H CH ₂ βTrp), 4.10 ( 2H, m -N-

-CH ₂ -ln), 5.25 (1H, m, CHα Trp), 6.85 (1 H, d, J = 2.0, H ₂ indole), 6.90-6.98 (2H, m, H ₅ indole), 7.01 (1 H , d, J = 2.0, H ₂ indole), 7.02-7.12 (2H, m, H ₆ indole), 7.30 (1 H, d, J = 8.2, H ₇ indole), 7.33 (1 H, d, J = 8.3, H ₇ indole), 7.40 (1 H, d, J = 7.9, H ₄ indole), 7.47 (1H, d, J = 7.8, H ₄ indole), 8.04 (2H, brs, NH ₂ Aib), 8.42 (1 H, s, H triazole), 9.01 (1 H, d, J = 8.0, NH Trp), 10.81 (1 H, s, NH indole), 10.90 (1 H, s, NH indole).

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4-methyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole -3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 96):

¹ N NMR (400 MHz1 DMSO-d ⁶ ):

δ (ppm) 1.20 (3H, s, CH ₃ Aib), 1.28 (3H, s, CH ₃ Aib), 3.32 (3H, d, N-CH ₃ ), 3.30-3.45 (2H, m, CH ₂ βTrp) , 4.22 (2H, S, -CH ₂ -ln), 5.30 (1 H, m, CHα Trp), 6.91 (1 H, t, J = 7.5, H ₅ indole), 6.94 (1 H, d, J = 7.5, H ₅ indole), 7.02 (1 H, t, J = 7.9, H ₆ indole), 7.05 (1 H, t, J = 7.9, H ₆ indole), 7.08 (1 H, d, J = 1.9, H ₂ indole), 7.12 (1H, d, J = 1.9, H ₂ indole), 7.29 (1 H, d, J = 8.1, H ₇ indole), 7.33 (1 H, d, J = 8.2, H ₇ indole ), 7.48 (1 H, d, J = 7.9, H ₄ indole), 7.57 (1 H, d, J = 7.9 H ₄ indole), 8.00 (2H, brs, NH ₂ Aib), 8.85 (1 H, d , J = 8.2, NH Trp), 10.82 (1 H, s, NH indole), 10.98 (1H, s, NH indole).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-methyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 97):

¹ N NMR (400 MHz, DMSO-d ⁶ ):

-

-ln), 3.36 (3Н, s, N-CH₃), 3.45-3.50 (2H, m, CH2β Trp), 5.30 (1 H, m, CH αTrp), 6.95-7.04 (2H, t, H₅ индол), 7.06-7.13 (2H, m, H₆ индол), 7.18 (2H, brs, H₂ индол), 7.34 (1 H, d, J=8.0, H₇ индол), 7.36 (1 H, d, J=8.0, H₇ индол), 7.48 (1H, d, J=7.8, H₄ индол), 7.58 (1 H, d, J=7.8, H₄ индол), 8.10 (2H, brs, NH₂ Aib), 8.95 (1 H, d, J=8.1, NH Trp), 10.95 (1 H, s, NH индол), 10.96 (1 H, s, NH индол).δ (ppm) 1.30 (3H, s, CH ₃ Aib), 1.40 (3H, s, CH ₃ Aib), 3.00-3.20 (4H, m, -

-

-ln), 3.36 (3H, s, N-CH ₃ ), 3.45-3.50 (2H, m, CH2β Trp), 5.30 (1 H, m, CH αTrp), 6.95-7.04 (2H, t, H ₅ indole ), 7.06-7.13 (2H, m, H ₆ indole), 7.18 (2H, brs, H ₂ indole), 7.34 (1 H, d, J = 8.0, H ₇ indole), 7.36 (1 H, d, J = 8.0, H ₇ indole), 7.48 (1H, d, J = 7.8, H ₄ indole), 7.58 (1 H, d, J = 7.8, H ₄ indole), 8.10 (2H, brs, NH ₂ Aib), 8.95 (1 H, d, J = 8.1, NH Trp), 10.95 (1 H, s, NH indole), 10.96 (1 H, s, NH indole).

¹³ C NMR (100 MHz, DMSO-d ⁶ ):

-

-индол), 24.1 (CH₃Aib), 24.3 (CH₃ Aib), 28.8 (

βTrp), 30.7 (-NCH₃), 46.2 (СН αTrp), 57.2 (Cq Aib), 110.2 (C₃ индол), 112.3 (2C₇ индол), 113.5 (C₃ индол), 118.9-119.2 (2C₅, 2C₄ индол), 121.9 (2C₆ индол), 123.6 (C₂ индол), 125.3 (C₂ индол), 127.7 (C₉ индол), 128.0 (C₉ индол), 136.9 (C₈ индол), 137.1 (C₈ индол), 155.3 (Cq триазол), 155.8 (Cq триазол), 172.2 (CO Aib).δ (ppm) 22.9-25.9 (-

-

-indole), 24.1 (CH ₃ Aib), 24.3 (CH ₃ Aib), 28.8 (

βTrp), 30.7 (-NCH ₃ ), 46.2 ( C H αTrp), 57.2 (Cq Aib), 110.2 (C ₃ indole), 112.3 (2C ₇ indole), 113.5 (C ₃ indole), 118.9-119.2 (2C ₅ , 2C ₄ indole), 121.9 (2C ₆ indole), 123.6 (C ₂ indole), 125.3 (C ₂ indole), 127.7 (C ₉ indole), 128.0 (C ₉ indole), 136.9 (C ₈ indole), 137.1 ( C ₈ indole), 155.3 (Cq triazole), 155.8 (Cq triazole), 172.2 (CO Aib).

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl ) ethyl) -2-amino-2-methylpropanamide (Compound 98):

¹ N NMR (400 MHz, DMSO-d ⁶ ):

δ (ppm) 1.31 (3H, s, CH ₃ Aib), 1.42 (3H, s, CH ₃ Aib), 3.19 (1 H, dd, J = 14.5, J = 9.6, 1H CH ₂ βTrp), 3.35 (1H , dd, J = 14.5, J = 5.3, 1 H CH ₂ βTrp), 4.15 (2H, s, CH ₂ indole), 5.26 (1H, m, CαH Trp), 6.95 (1 H, t, H ₅ Trp) 6.96 (1 H, t, H ₅ indole), 7.05 (1 H, 1, H ₆ Trp), 7.06 (1 H, s, H ₂ Trp), 7.07 (1 H, t, H ₆ indole), 7.21 (1 H, s, H ₂ indole), 7.32 (1 H, d, H ₇ Indole), 7.37 (1 H, d, H ₇ indole), 7.51 (1 H, d, J = 7.8, H ₄ indole) 7.58 (1H, d, J = 7.8, H ₄ Trp), 8.00 (2H, s, NH ₂ Aib), 8.64 (1 H, d, J = 8.7, NH Trp), 10.77 (1 H, s, NH indole Trp), 10.92 (1 H, s, NH indole).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

δ (ppm) 22.9 (CH ₂ indole), 23.2 (CH ₃ Aib), 23.3 (CH ₃ Aib), 29.4 (Cβ Trp), 48.3 (Cα Trp), 56.3 (Cq Aib), 109.7 (C ₃ indole), 110.3 (C ₃ Trp), 111.2 (C ₇ Trp), 111.3 (C ₇ indole), 118.1 (C ₄ Trp, C ₅ Trp), 118.3 (C ₄ indole), 118.4 (C ₅ indole), 120.7 (C ₆ Trp), 121.0 (C ₆ indole), 123.4 (C ₂ indole), 123.6 (C ₂ Trp), 126.8 (C ₉ indole), 127.1 (C ₉ Trp), 136.0 (C ₈ Trp), 136.2 (C ₈ indole) ), 157.5 (Cq triazole), 161.7 (Cq triazole), 170.8 (CO Aib).

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 99):

¹ H NMR (400 MHz, DMSO-d ⁶ ):

δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.29 (3H, s, CH ₃ Aib), 3.25 (1 H, dd, J = 14.3, J = 5.6, 1 H CH ₂ βTrp), 3.38 ( 1 H, dd, J = 14.3, J = 9.1, 1 H CH ₂ αTrp), 3.68 (3H, s, OCH ₃ ), 3.72 (3H, s, OCH ₃ ), 4.10 (1 H, d, J = 16.5 , 1 H CH ₂ indole), 4.16 (1H, d, J = 16.5, 1 H CH ₂ indole), 4.96 (1 H, d, J = 16.8, 1 H CH ₂ about, para-dimethoxybenzyl), 5.12 (1 H, d, J = 16.8, 1 H CH ₂ о, para-dimethoxybenzyl), 5.16 (1H, m, CαH Trp), 6.21 (1H, dd, J = 8.5, J = 2.1, H ₅ о, para-dimethoxybenzyl ), 6.27 (1 H, d, J = 8.5, H ₆ about, para-dimethoxybenzyl), 6.57 (1H, d, J = 2.1, H ₃ about, para-dimethoxybenzyl), 6.83 (1H, t, H ₅ Trp ), 6.94 (1H, t, H ₅ indole), 7.02 (1H, t, H ₆ indole), 7.05 (1 H, t, H ₂ indole), 7.06 (1 H, t, H ₆ indole), 7.07 ( 1 H, s, H ₂ Trp), 7.07 (1H, t , H ₄ Trp), 7.31 (1 H, d, H ₇ Trp), 7.33 (1 H, d, H ₇ indole), 7.36 (1 H, d, J = 7.8, H ₄ indole), 8.00 (2H, brs, NH ₂ Aib), 8.92 (1 H, d, J = 8.2, NH Trp), 10.79 (1H, s, NH indole Trp), 10.89 (1 H, s, NH indole).

¹³ C NMR (400 MHz, DMSO-d ⁶ ):

о,пара-диметоксибензил), 45.1 (Cα Trp), 55.2 (OCH₃), 55.4 (OCH₃), 56.2 (Cq Aib), 98.5 (C₃ о,пара-диметоксибензил), 104.6 (C₅ о,пара-диметоксибензил), 107.9 (C₃ индол), 109.5 (C₃ Trp), 111.2 (C₇ Trp), 111.3 (C₇ индол), 115.1 (C₁ о,пара-диметоксибензил), 117.8 (C₄ Trp), 118.1 (C₅ Trp), 118.3 (C₄ индол), 118.4 (C₅ индол), 120.8 (C₆ Trp), 121.1 (C₆ индол), 123.5 (C₂ индол), 124.3 (C₂ Trp), 126.6 (C₉ индол), 126.8 (C₉ Trp), 127.2 (C₆ о,пара-диметоксибензил), 136.0 (C₈ Trp), 136.2 (C₈ индол), 157.5 (Cq триазол), 154.9 (Cq триазол), 157.2 (C₂ о,пара-диметоксибензил), 160.3 (C₄ о,пара-диметоксибензил), 171.2 (CO Aib).δ (ppm) 21.2 (CH ₂ -indole), 23.1 (CH ₃ Aib), 23.2 (CH ₃ Aib), 28.6 (Cβ Trp), 41.4 (N-

o, para-dimethoxybenzyl), 45.1 (Cα Trp), 55.2 (OCH ₃ ), 55.4 (OCH ₃ ), 56.2 (Cq Aib), 98.5 (C ₃ o, para-dimethoxybenzyl), 104.6 (C ₅ o, para- dimethoxybenzyl), 107.9 (C ₃ indole), 109.5 (C ₃ Trp), 111.2 (C ₇ Trp), 111.3 (C ₇ indole), 115.1 (C ₁ o, para-dimethoxybenzyl), 117.8 (C ₄ Trp), 118.1 (C ₅ Trp), 118.3 (C ₄ indole), 118.4 (C ₅ indole), 120.8 (C ₆ Trp), 121.1 (C ₆ indole), 123.5 (C ₂ indole), 124.3 (C ₂ Trp), 126.6 ( C ₉ indole), 126.8 (C ₉ Trp), 127.2 (C ₆ about, para-dimethoxybenzyl), 136.0 (C ₈ Trp), 136.2 (C ₈ indole), 157.5 (Cq triazole), 154.9 (Cq triazole), 157.2 (C ₂ about, para-dimethoxybenzyl), 160.3 (C ₄ about, para-dimethoxybenzyl), 171.2 (CO Aib).

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (N-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 101):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-индол), 5.09 (3Н, m, CH αTrp и

-пара-метоксибензил), 6.70 (4H, s, СНаr пара-метоксибензил), 6.78 (2Н, m, Н₅ индол и Н₅ Trp), 6.93 (2Н, m, Н₆ индол и Н₆ Trp), 7.01-7,06 (3Н, m, Н₂ индол, Н₂ и Н₄ Trp), 7.31 (3Н, m, Н₄ и Н₇ индол, Н₇ Trp), 7.98 (3Н, brs, NH₂ Aib), 8.92 (1 Н, d, J=8 Hz, NH амид), 10.77 (1H, s, NH индол), 10.89 (1 H, s, NH индол Trp).δ (ppm) 1.22 (3H, s, CH ₃ Aib), 1.25 (3H, s, CH ₃ Aib), 3.22 (1H, dd, J = 14 Hz and 6 Hz, CH ₂ βTrp), 3.34 (1 H, dd, J = 14 Hz and 9 Hz, CH ₂ βTrp), 3.68 (3Н, s, OCH ₃ ), 4.11 (2H, m,

-indole), 5.09 (3H, m, CH αTrp and

-para-methoxybenzyl), 6.70 (4H, s, CHa-para-methoxybenzyl), 6.78 (2H, m, H ₅ indole and H ₅ Trp), 6.93 (2H, m, H ₆ indole and H ₆ Trp), 7.01- 7.06 (3H, m, H ₂ indole, H ₂ and H ₄ Trp), 7.31 (3H, m, H ₄ and H ₇ indole, H ₇ Trp), 7.98 (3H, brs, NH ₂ Aib), 8.92 (1 H, d, J = 8 Hz, NH amide), 10.77 (1H, s, NH indole), 10.89 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 21.7 ( C H ₂ -indole), 23.5 (CH ₃ Aib), 23.7 (CH ₃ Aib), 28.9 (CH ₂ βTrp), 45.6 (CH αTrp), 45.8 ( C H ₂ -paramethoxybenzyl) 55.5 (OCH ₃ ), 56.7 (Cq Aib), 108.1 (C ₃ indole), 109.7 (C ₃ Trp), 111.7 (C ₇ Trp), 111.9 (C ₇ indole), 114.5 (C ₃ and C ₅ para- methoxybenzyl), 118.3 (C ₄ Trp), 118.7 (C ₄ indole), 118.8 (C ₅ Indole), 118.9 (C ₅ Trp), 121.3 (C ₆ indole), 121.6 (C ₆ Trp), 124.2 (C ₂ indole ), 125.3 (C ₂ Trp), 127.1 (C ₉ indole), 127.2 (C ₉ Trp), 127.6 (C ₁ para-methoxybenzyl), 127.8 (C ₂ and C ₆ para-methoxybenzyl), 136.4 (C ₈ Trp) 136.7 (C ₈ indole), 154.2 (Cq triazole), 155.2 (Cq triazole), 159.2 (C ₄ para-methoxybenzyl), 171.9 (CO Aib).

(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 102):

¹ N NMR (400 MHz, DMSO-d ⁶ ):

δ (ppm) 1.30 (3H, s, CH ₃ Aib), 1.33 (3H, s, CH ₃ Aib), 3.26 (1 H, dd, J = 14.2, J = 5.9, 1 H CH ₂ βTrp), 3.38 ( 1 H, dd, J = 14.2, J = 8.7, 1 H CH ₂ αTrp), 3.69 (3H, s, OCH ₃ ), 3.72 (3H, s, OCH ₃ ), 4.02 (2H, s, CH ₂ benzyl) , 4.87 (1 H, d, J = 16.7, 1 H CH ₂ о, para-dimethoxybenzyl), 5.08 (1H, d, J = 16.7, 1 H CH ₂ о, para-dimethoxybenzyl), 5.17 (1 H, m , CαH Trp), 6.24 (1 H, d, J = 8.4, J = 1.7, H ₅ about, para-dimethoxybenzyl), 6.28 (1 H, d, J = 8.4, H ₆ about, para-dimethoxybenzyl), 6.56 (1 H, d, J = 1.7, H ₃ about, para-dimethoxybenzyl), 6.85 (1 H, t, J = 7.5, H ₅ Trp), 7.02 (1 H, t, H ₆ Trp), 7.07 (2H , m, H ₂ , H ₆ benzyl), 7.08 (1 H, s, H ₂ Trp), 7.09 (1 H, d, H ₄ Trp), 7.16-7.29 (3H, m, H ₃ , H ₄ , H ₅ benzyl), 7.31 (1 H, d, J = 8.2, H ₇ Trp), 8.01 (2H, s, NH ₂ Aib), 8.92 (1 H, d, J = 7.9, NH Trp), 11.79 (1 H , s, NH indole Trp).

¹³ C NMR (400 MHz.DMSO-d ⁶ ):

-бензил), 41.3 (СН₂-о,пара-диметоксибензил), 45.2 (Cα Trp), 55.2 (OCH₃), 55.4 (OCH₃), 56.2 (Cq Aib), 98.5 (C₃ о,пара-диметоксибензил), 104.7 (C₅ о,пара-диметоксибензил), 109.5 (C₃ Trp), 111.3 (C₇ Trp), 115.1 (C₁ о,пара-диметоксибензил), 117.8 (C₄ Trp), 118.2 (C₅ Trp), 120.8 (C₆ Trp), 124.3 (C₂ Trp), 126.5 (C₂, C₆ бензил), 126.8 (C₉ Trp), 127.3 (C₆ о,пара-диметоксибензил), 128.3 (C₃, C₄, C₅ бензил), 135.8 (С, бензил), 136.0 (C₈ Trp), 153.4 (Cq триазол), 155.0 (Cq триазол), 157.2 (C₂ о,пара-диметоксибензил), 160.3 (C₄ о,пара-диметоксибензил), 171.3 (CO Aib).δ (ppm) 23.2 (2CH ₃ Aib), 28.7 (Cβ Trp), 30.2 (

-benzyl), 41.3 ( C H ₂ -o, para-dimethoxybenzyl), 45.2 (Cα Trp), 55.2 (OCH ₃ ), 55.4 (OCH ₃ ), 56.2 (Cq Aib), 98.5 (C ₃ o, para-dimethoxybenzyl ), 104.7 (C ₅ о, para-dimethoxybenzyl), 109.5 (C ₃ Trp), 111.3 (C ₇ Trp), 115.1 (C ₁ о, para-dimethoxybenzyl), 117.8 (C ₄ Trp), 118.2 (C ₅ Trp ), 120.8 (C ₆ Trp), 124.3 (C ₂ Trp), 126.5 (C ₂ , C ₆ benzyl), 126.8 (C ₉ Trp), 127.3 (C ₆ about, para-dimethoxybenzyl), 128.3 (C ₃ , C ₄ , C ₅ benzyl), 135.8 (C, benzyl), 136.0 (C ₈ Trp), 153.4 (Cq triazole), 155.0 (Cq triazole), 157.2 (C ₂ about, para-dimethoxybenzyl), 160.3 (C ₄ about, para-dimethoxybenzyl), 171.3 (CO Aib).

(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole -3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 104):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.74 (1Н, m, СН₂ βTrp), 3.92 (1 Н, m, СН₂ αTrp), 3.99 (2Н, s, СН₂-индол), 5.21 (1 Н, m, СН αTrp), 6.74 (2Н, m, Н₅ индол и Н₅ Trp), 6.90 (1 Н, t, J₀=8 Hz, Н₆ Trp), 6.92 (1 Н, t, J₀=8 Hz, H₆ индол), 7.01-7.06 (4H, m, H₂ и H₆ фенил, H₂ индол и H₂ Trp), 7.16 (3Н, m, H₃, H₄ и Н₅ фенил), 7.27 (1Н, d, J₀=8 Hz, Н₄ Trp), 7.32 (1 Н, d, J₀=8 Hz, H₇ Trp), 7.36 (1 H, d, J₀=8 Hz, H₇ индол), 7.50 (1H, d, J₀=8 Hz, H₄ индол), 7.99 (3Н, brs, NH₂ Aib), 9.02 (1H, s, J=8 Hz, NH амид), 10.79 (1 H, s, NH индол Trp), 10.94 (1 H, s, NH индол).δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.29 (3H, s, CH ₃ Aib), 2.39-2.53 (4H, m,

-

-phenyl), 3.74 (1Н, m, СН ₂ βTrp), 3.92 (1 Н, m, СН ₂ αTrp), 3.99 (2Н, s, СН ₂ -indole), 5.21 (1 Н, m, СН αTrp), 6.74 (2H, m, H ₅ indole and H ₅ Trp), 6.90 (1 H, t, J ₀ = 8 Hz, H ₆ Trp), 6.92 (1 H, t, J ₀ = 8 Hz, H ₆ indole) 7.01-7.06 (4H, m, H ₂ and H ₆ phenyl, H ₂ indole and H ₂ Trp), 7.16 (3H, m, H ₃ , H ₄ and H ₅ phenyl), 7.27 (1H, d, J ₀ = 8 Hz, H ₄ Trp), 7.32 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 7.36 (1 H, d, J ₀ = 8 Hz, H ₇ indole), 7.50 (1H, d , J ₀ = 8 Hz, H ₄ indole), 7.99 (3H, brs, NH ₂ Aib), 9.02 (1H, s, J = 8 Hz, NH amide), 10.79 (1 H, s, NH indole Trp), 10.94 (1 H, s, NH indole).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-индол), 23.5 (CH₃ Aib), 23.8 (CH₃ Aib), 29.5 (CH₂ βTrp), 35.8 (СН₂-

-фенил), 44.5 (

-СН₂-фенил), 45.8 (CH αTrp), 56.7 (Cq Aib), 108.5 (C₃ индол), 109.9 (C₃ Trp), 114.0 (C₇ индол и C₇ Trp), 118.4 (C₄ Trp), 118.8 (C₄ индол и C₅ Trp), 119.0 (C₅ индол), 121.4 (C₆ Trp), 121.7 (C₆ индол), 124.0 (C₂ индол и C₂ Trp), 127.1 (C₄ фенил), 127.7 (C₉ индол и C₉ Trp), 128.8 (C₂ и C₆ фенил), 129.1 (С₃ и С₅ фенил), 136.5 (С₈ Trp), 136.6 (С₈ индол), 137.5 (С₁ фенил), 153.6 (Cq триазол), 155.0 (Cq триазол), 171.8 (СО Aib).δ (ppm) 21.4 (

-indole), 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 29.5 (CH ₂ βTrp), 35.8 (CH ₂ -

phenyl), 44.5 (

-CH ₂ -phenyl), 45.8 (CH αTrp), 56.7 (Cq Aib), 108.5 (C ₃ Indole), 109.9 (C ₃ Trp), 114.0 (C ₇ indole and C ₇ Trp), 118.4 (C ₄ Trp) 118.8 (C ₄ indole and C ₅ Trp), 119.0 (C ₅ Indole), 121.4 (C ₆ Trp), 121.7 (C ₆ indole), 124.0 (C ₂ indole and C ₂ Trp), 127.1 (C ₄ phenyl) 127.7 (C ₉ indole and C ₉ Trp), 128.8 (C ₂ and C ₆ phenyl), 129.1 (C ₃ and C ₅ phenyl), 136.5 (C ₈ Trp), 136.6 (C ₈ indole), 137.5 (C ₁ phenyl), 153.6 (Cq triazole), 155.0 (Cq triazole), 171.8 (CO Aib).

(R) -N- (1- (5-benzyl-4- (2,2-diphenylethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 106):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

(Phe)₂), 4.21 (1 H, dd, J=14 Hz и 8 Hz,

-CH(Phe)₂), 4.51 (1 H, dd, J=14 Hz и 8 Hz,

-CH(Phe)₂), 5.08 (1 H, m, CH αTrp), 6.72 (2H, m, H₂ и H₆ бензил), 6.86-6.93 (5H, m, H₃, H₄ и H₅ бензил, H₅ и H₆ Trp), 7.03 (1 H, s, H₂ Trp), 7.06-7.25 (СНаr фенил из CH(Phe)₂), 7.33 (1 H, d, J₀=8 Hz, H₄ Trp), 7.47(1 H, d, J₀=8 Hz, H₇ индол), 8.10 (3Н, brs, NH₂ Aib), 8.98 (1 H, d, J=8 Hz, NH амид), 10.94 (1 H, s, NH индол Trp).δ (ppm) 1.29 (3H, s, CH ₃ Aib), 1.34 (3H, s, CH ₃ Aib), 3.37 (4H, m, CH ₂ βTrp and CH ₂ benzyl), 3.74 (1 H, t, J = 7 Hz, CH ₂ -

(Phe) ₂ ), 4.21 (1 H, dd, J = 14 Hz and 8 Hz,

-CH (Phe) ₂ ), 4.51 (1 H, dd, J = 14 Hz and 8 Hz,

-CH (Phe) ₂ ), 5.08 (1 H, m, CH αTrp), 6.72 (2H, m, H ₂ and H ₆ benzyl), 6.86-6.93 (5H, m, H ₃ , H ₄ and H ₅ benzyl , H ₅ and H ₆ Trp), 7.03 (1 H, s, H ₂ Trp), 7.06-7.25 (CH-phenyl from CH (Phe) ₂ ), 7.33 (1 H, d, J ₀ = 8 Hz, H ₄ Trp), 7.47 (1 H, d, J ₀ = 8 Hz, H ₇ indole), 8.10 (3H, brs, NH ₂ Aib), 8.98 (1 H, d, J = 8 Hz, NH amide), 10.94 ( 1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-бензил), 46.0 (CH αTrp), 47.7 (

-CH(Phe)₂), 51.3 (

(Phe)₂), 56.8 (Cq Aib), 109.8 (C₃ Trp),112.0 (C₇ Trp), 118.5 (C₄ Trp), 119.0 (C₅ Trp), 121.5 (C₆ Trp), 124.8 (C₂ Trp),127.0 (C₄ фенил из CH(Phe)₂), 127.4 (C₉ Trp, C₂ и C₆ бензил), 128.3 (C₂ и C₆ фенил из CH(Phe)₂), 128.8-129.1 (C₃ и C₅ фенил из CH(Phe)₂, C₃, C₄ и C₅ бензил), 136.2 (С, бензил), 136.5 (C₈ Trp), 141.0 (С₁ фенил из СН(Phе)₂), 153.5 (Cq триазол), 155.1 (Cq триазол), 172.0 (СО Aib).α (ppm) 23.5 (CH ₃ Aib), 23.7 (CH ₃ Aib), 29.4 (CH ₂ βTrp), 30.1 (

-benzyl), 46.0 (CH αTrp), 47.7 (

-CH (Phe) ₂ ), 51.3 (

(Phe) ₂ ), 56.8 (Cq Aib), 109.8 (C ₃ Trp), 112.0 (C ₇ Trp), 118.5 (C ₄ Trp), 119.0 (C ₅ Trp), 121.5 (C ₆ Trp), 124.8 (C ₂ Trp), 127.0 (C ₄ phenyl from CH (Phe) ₂ ), 127.4 (C ₉ Trp, C ₂ and C ₆ benzyl), 128.3 (C ₂ and C ₆ phenyl from CH (Phe) ₂ ), 128.8-129.1 (C ₃ and C ₅ phenyl from CH (Phe) ₂ , C ₃ , C ₄ and C ₅ benzyl), 136.2 (C, benzyl), 136.5 (C ₈ Trp), 141.0 (C ₁ phenyl from CH (Phе) ₂ ), 153.5 (Cq triazole), 155.1 (Cq triazole), 172.0 (CO Aib).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,2-diphenylethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 107):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-индол), 2.30 (1 H, m, СН₂-

-индол), 2.78 (2Н, m,

-СН₂-индол), 3.35 (1 Н, dd, J=14 Hz и 7 Hz, CH₂ βTrp), 3.46 (1 H, dd, J=14 Hz и 9 Hz, CH₂ βTrp), 3.58 (1 H, t, J=7 Hz, СН₂-CH(Phe)₂), 4.14 (1 H, dd, J=14 Hz и 8 Hz,

-CH(Phe)₂), 4.39 (1 H, dd, J=14 Hz и 7 Hz,

-CH(Phe)₂), 5.12 (1 H, m, CH αTrp), 6.50 (2H, m, H₅ индол и H₅ Trp), 6.76 (2H, m, H₆ индол и Н₆ Trp), 6.87 (2Н, m, Н₂ индол и Н₂ Trp), 6.89-6.96 (2Н, m, Н₄ фенил), 7.03-7,15 (8Н, m, Н₂, Н₃, Н₅ и Н₆ фенил), 7.33 (3Н, m, Н₄ индол, Н₄ и Н₇ Trp), 7.47 (1 Н, d, J=8 Hz, Н₇ индол), 8.11 (3Н, brs, NH₂ Aib), 9.04 (1 Н, d, J=8 Hz, NH амид), 10.76 (1 H, s, NH индол), 10.96 (1 H, s, NH индол Trp).δ (ppm) 1.34 (3H, s, CH ₃ Aib), 1.38 (3H, s, CH ₃ Aib), 2.06 (1 H, m, CH ₂ -

-indole), 2.30 (1 H, m, CH ₂ -

-indole), 2.78 (2H, m,

-CH ₂ -indole), 3.35 (1 H, dd, J = 14 Hz and 7 Hz, CH ₂ βTrp), 3.46 (1 H, dd, J = 14 Hz and 9 Hz, CH ₂ βTrp), 3.58 (1 H, t, J = 7 Hz, CH ₂ -C H (Phe) ₂ ), 4.14 (1 H, dd, J = 14 Hz and 8 Hz,

-CH (Phe) ₂ ), 4.39 (1 H, dd, J = 14 Hz and 7 Hz,

-CH (Phe) ₂ ), 5.12 (1 H, m, CH αTrp), 6.50 (2H, m, H ₅ indole and H ₅ Trp), 6.76 (2H, m, H ₆ indole and H ₆ Trp), 6.87 (2H, m, H ₂ indole and H ₂ Trp), 6.89-6.96 (2H, m, H ₄ phenyl), 7.03-7.15 (8H, m, H ₂ , H ₃ , H ₅ and H ₆ phenyl) 7.33 (3H, m, H ₄ indole, H ₄ and H ₇ Trp), 7.47 (1 H, d, J = 8 Hz, H ₇ indole), 8.11 (3H, brs, NH ₂ Aib), 9.04 (1 H, d, J = 8 Hz, NH amide), 10.76 (1 H, s, NH indole), 10.96 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-индол), 23.6 (CH₃ Aib), 23.8 (CH₃ Aib), 24.9 (

-СН₂-индол), 29.6 (CH₂ βTrp), 46.1 (CH αTrp)), 47.5 (

-CH(Phe)₂), 51.5 (CH₂-

(Phe)₂), 56.8 (Cq Aib), 109.8 (C₃Trp), 111.8 (C₇ Trp), 112.1 (C₇ индол), 113.5 (C₃ индол), 118.4 (C₄ Trp), 118.7 (C₄ и C₅ индол), 119.0 (C₅ Trp), 121.4 (C₆ индол и C₆ Trp), 122.8 (C₂ индол), 125.0 (C₂ Trp), 127.2 (C₉ индол и C₉ Trp), 127.3 (C₄ фенил), 128.2 (C₂ и C₆ фенил), 128.7 (C₃ и C₅ фенил), 136.6 (C₈ индол и C₈ Trp), 141.0 (С₁ фенил), 154.6 (2 Cq триазол), 172.0 (CO Aib).δ (ppm) 22.4 (CH ₂ -

-indole), 23.6 (CH ₃ Aib), 23.8 (CH ₃ Aib), 24.9 (

-CH ₂ -indole), 29.6 (CH ₂ βTrp), 46.1 (CH αTrp)), 47.5 (

-CH (Phe) ₂ ), 51.5 (CH ₂ -

(Phe) ₂ ), 56.8 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 112.1 (C ₇ indole), 113.5 (C ₃ indole), 118.4 (C ₄ Trp), 118.7 (C ₄ and C ₅ indole), 119.0 (C ₅ Trp), 121.4 (C ₆ indole and C ₆ Trp), 122.8 (C ₂ indole), 125.0 (C ₂ Trp), 127.2 (C ₉ indole and C ₉ Trp), 127.3 (C ₄ phenyl), 128.2 (C ₂ and C ₆ phenyl), 128.7 (C ₃ and C ₅ phenyl), 136.6 (C ₈ indole and C ₈ Trp), 141.0 (C ₁ phenyl), 154.6 (2 Cq triazole ), 172.0 (CO Aib).

(R) -N- (1- (4,5-dibenzyl-4H-1,2,4-thiazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2 methylpropanamide (Compound 109):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-фенил), 5.10 (3Н, m, N-

-фенил и CH αTrp), 6.77 (3Н, m, H₅ Trp, H₂ и Н₆ фенил из N-СН₂-фенил), 6.99 (2Н, m, Н₂ и Н₆ Trp), 7.01-7.07 (3Н, m, Н₄ Trp, Н₂ и Н₆ из С-СН₂-фенил), 7.15-7.23 (6Н, m, Н₃, Н₄ и Н₅ фенил из N-СН₂-фенила и из С-СН₂-фенила), 7.25 (1Н, d, J=8 Hz, Н₇ Trp), 8.01 (3Н, brs, NH₂ Aib), 8,91 (1 H, d, J=8 Hz, NH амид), 10.78 (1 H, s, NH индол Trp).α (ppm) 1.23 (3H, s, CH ₃ Aib), 1.26 (3H, s, CH ₃ Aib), 3.23 (1 H, dd, J = 14 Hz and 6 Hz, CH ₂ βTrp), 3.35 (1 H , dd, J = 14 Hz and 9 Hz, CH ₂ βTrp), 3.99 (2H, s, С-

-phenyl), 5.10 (3H, m, N-

phenyl and CH αTrp), 6.77 (3H, m, H ₅ Trp, H ₂ and H ₆ phenyl from N-CH ₂ phenyl), 6.99 (2H, m, H ₂ and H ₆ Trp), 7.01-7.07 ( 3H, m, H ₄ Trp, H ₂ and H ₆ from C-CH ₂ -phenyl), 7.15-7.23 (6H, m, H ₃ , H ₄ and H ₅ phenyl from N-CH ₂ -phenyl and from C- CH ₂ -phenyl), 7.25 (1H, d, J = 8 Hz, H ₇ Trp), 8.01 (3H, brs, NH ₂ Aib), 8.91 (1 H, d, J = 8 Hz, NH amide) 10.78 (1 H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-фенил), 45.7 (СН αTrp), 46.1 (N-CH₂-фeнил), 56.7 (Cq Aib), 109.8 (C₃ Trp), 111.7 (C₇ Trp), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.2 (C₆ Trp), 124.8 (C₂ Trp), 126.3 (C₂ и C₆ фенил из N-СН₂-фенила), 127.0 (C₂ и C₆ фенил из С-СН₂-фенила), 127.2 (С₉ Trp), 128.0 (С₄ фенил из N-СН₂-фенила), 128.8 (С₃, С₄ и С₅ фенил из С-СН₂-фенила), 128.9 (С₃ и С₅ фенил из N-СН₂-фенила), 135.8 (С₁ фенил из N-СН₂-фенила), 136.2 (С₁ фенил из С-СН₂-фенила), 136.4 (С₈ Trp), 153.9 (Cq триазол), 155.3 (Cq триазол), 171.9 (СО Aib).δ (ppm) 23.5 (CH ₃ Aib), 23.7 (CH ₃ Aib), 29.0 (CH ₂ βTrp), 30.6 (C-

phenyl), 45.7 (CH αTrp), 46.1 (N-CH ₂ phenyl), 56.7 (Cq Aib), 109.8 (C ₃ Trp), 111.7 (C ₇ Trp), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.2 (C ₆ Trp), 124.8 (C ₂ Trp), 126.3 (C ₂ and C ₆ phenyl from N-CH ₂ phenyl), 127.0 (C ₂ and C ₆ phenyl from C-CH ₂ phenyl ), 127.2 (C ₉ Trp), 128.0 (C ₄ phenyl from N-CH ₂ phenyl), 128.8 (C ₃ , C ₄ and C ₅ phenyl from C-CH ₂ phenyl), 128.9 (C ₃ and C ₅ phenyl from N-CH ₂ phenyl), 135.8 (C ₁ phenyl from N-CH ₂ phenyl), 136.2 (C ₁ phenyl from C-CH ₂ phenyl), 136.4 (C ₈ Trp), 153.9 (Cq triazole) 155.3 (Cq triazole), 171.9 (CO Aib).

(R) -N- (1- (5-benzyl-4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide (Compound 110):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

), 0.87 (4H, m, 2CH₂), 0.95 (2H, m, СН ₂-CH₃), 1.00 (2H, m, N-CH₂-CH ₂), 1.36 (6H, s, CH₃ Aib), 3.36 (1H, dd, ³J=14 Hz и 7 Hz, CH₂ βTrp), 3.41 (1H, dd, ³J=14 Hz и 7 Hz, CH βTrp), 3.50 (1H, m, N-CH ₂), 3.65 (1 H, m, N-

), 4.11 (2H, s,

-бензил), 5.14 (1H, m, СН αTrp), 6.90 (1H, t, J₀=7 Hz, H₅ Trp), 7.01 (1 H, t, J₀=7 Hz, H₆ Trp), 7.04 (1 H, s, H₂ Trp), 7.09 (2H, m, H₂ и H₆ бензил), 7.17-7.29 (4H, m, H₄ Trp, H₃, H₄ и H₅ бензил), 7.47 (1 H, d, J₀=8 Hz, H₇ Trp), 8.10 (3H, brs, NH₂ Aib), 9.05 (1 H, d, J=7 Hz, NH амид), 10.84 (1 H, s, NH индол Trp).δ (ppm) 0.71 (3H, t, ³ J = 7 Hz, (CH ₂ ) ₅ -

), 0.87 (4H, m, 2CH ₂ ), 0.95 (2H, m, C H ₂ -CH ₃ ), 1.00 (2H, m, N-CH ₂ -C H ₂ ), 1.36 (6H, s, CH ₃ Aib), 3.36 (1H, dd, ³ J = 14 Hz and 7 Hz, CH ₂ βTrp), 3.41 (1H, dd, ³ J = 14 Hz and 7 Hz, CH βTrp), 3.50 (1H, m, NC H ₂ ), 3.65 (1 H, m, N-

), 4.11 (2H, s,

-benzyl), 5.14 (1H, m, CH αTrp), 6.90 (1H, t, J ₀ = 7 Hz, H ₅ Trp), 7.01 (1 H, t, J ₀ = 7 Hz, H ₆ Trp), 7.04 (1 H, s, H ₂ Trp), 7.09 (2H, m, H ₂ and H ₆ benzyl), 7.17-7.29 (4H, m, H ₄ Trp, H ₃ , H ₄ and H ₅ benzyl), 7.47 ( 1 H, d, J ₀ = 8 Hz, H ₇ Trp), 8.10 (3H, brs, NH ₂ Aib), 9.05 (1 H, d, J = 7 Hz, NH amide), 10.84 (1 H, s, NH Indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

), 22.1 (CH₂-CH₃), 23.8 (CH₃ Aib), 23.5 (CH₃ Aib), 25.8 (CH₃-CH₂-CH₂-CH₂), 29.5 (CH₂ βTrp), 30.3 (N-CH₂-

), 30.8 (

-бензил и CH₃-CH₂-CH₂), 43.3 (N-CH₂-CH₂), 46.1 (СН αTrp), 56.8 (Cq Aib), 109.6 (C₃ Trp), 111.9 (C₇ Trp), 118.2 (C₄ Trp), 118.8 (C₅ Trp), 121.4 (C₆ Trp), 124.7 (C₂ Trp), 127.2 (C₂ и C₆ бензил), 127.3 (C₉ Trp), 128.8 (C₃, C₄ и C₅ бензил), 136.2 (С₁ бензил), 136.5 (C₈ Trp), 153.1 (Cq триазол), 155.1 (Cq триазол), 171.9 (CO Aib).δ (ppm) 14.1 ((CH ₂ ) ₅ -

), 22.1 ( C H ₂ -CH ₃ ), 23.8 (CH ₃ Aib), 23.5 (CH ₃ Aib), 25.8 (CH ₃ -CH ₂ -CH ₂ - C H ₂ ), 29.5 (CH ₂ βTrp), 30.3 (N-CH ₂ -

), 30.8 (

-benzyl and CH ₃ -CH ₂ - C H ₂ ), 43.3 (N- C H ₂ -CH ₂ ), 46.1 (CH αTrp), 56.8 (Cq Aib), 109.6 (C ₃ Trp), 111.9 (C ₇ Trp ), 118.2 (C ₄ Trp), 118.8 (C ₅ Trp), 121.4 (C ₆ Trp), 124.7 (C ₂ Trp), 127.2 (C ₂ and C ₆ benzyl), 127.3 (C ₉ Trp), 128.8 (C ₃ , C ₄ and C ₅ benzyl), 136.2 (C ₁ benzyl), 136.5 (C ₈ Trp), 153.1 (Cq triazole), 155.1 (Cq triazole), 171.9 (CO Aib).

(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 111):

¹ N NMR (400 MHz, DMSO-d ⁶ , 300 K):

-индол), 3.37 (2Н, m, СН₂ βTrp), 3.76-3.90 (4Н, m,

-бензил и

-СН₂-индол), 5.25 (1 Н, m, СН αTrp), 6.88 (2Н, t, J₀=7 hz, Н₅ индол и Н₅Trp), 6.95 (2Н, t, J₀=7 Hz, Н₆ индол и Н₆Trp), 7.03 (4Н, m, Н₂Trp, Н₂ индол, Н₂ и Н₆ бензил), 7.16 (2Н, d, J₀=8 Hz, Н₄ индол и Н₄ Trp), 7.20-7,30 (4Н, 3, Н₇ индол, Н₃, Н₄ и Н₅ бензил), 7.47 (1 Н, d, J₀=8 Hz, Н₇ Trp), 8.05 (3Н, brs, NH₂ Aib), 9.05 (1 H, d, J=8 Hz, NH амид), 10.83 (1 H, s, NH индол), 10.88 (1 H, s, NH индол Trp).δ (ppm) 1.31 (3H, s, CH ₃ Aib), 1.35 (3H, s, CH ₃ Aib), 2.51 (2H, m, CH ₂ -

-indole), 3.37 (2H, m, CH ₂ βTrp), 3.76-3.90 (4H, m,

benzyl and

-CH ₂ -indole), 5.25 (1 Н, m, СН αTrp), 6.88 (2Н, t, J ₀ = 7 hz, Н ₅ indole and Н ₅ Trp), 6.95 (2Н, t, J ₀ = 7 Hz , H ₆ indole and H ₆ Trp), 7.03 (4H, m, H ₂ Trp, H ₂ indole, H ₂ and H ₆ benzyl), 7.16 (2H, d, J ₀ = 8 Hz, H ₄ indole and H ₄ Trp), 7.20-7.30 (4Н, 3, Н ₇ indole, Н ₃ , Н ₄ and Н ₅ benzyl), 7.47 (1 Н, d, J ₀ = 8 Hz, Н ₇ Trp), 8.05 (3Н, brs, NH ₂ Aib), 9.05 (1 H, d, J = 8 Hz, NH amide), 10.83 (1 H, s, NH indole), 10.88 (1 H, s, NH indole Trp).

¹³ C NMR (100 MHz, DMSO-d ⁶ , 300 K):

-бензил и СН₂-

-индол), 44.1 (

-СН₂-индол), 46.1 (СН αTrp), 56.8 (Cq Aib), 109.8 (С₃ Trp), 109.9 (С₃ индол), 111.9 (С₇ индол и С₇ Trp), 118.3 (С₄ Trp), 118.4 (С₄ индол), 118.9 (С₅ индол и С₅ Trp), 121.3 (С₆ Trp), 121.5 (С₆ индол), 123.7 (С₂ индол), 124.7 (С₂ Trp), 127.0 (С₉ индол), 127.2 (С₂ и С₆ бензил), 127.4 (С₉ Trp), 128.8 (С₃ и С₅ бензил), 129.0 (С₄ бензил), 136.3 (С₁ бензил), 136.4 (С₈ индол и C₈Trp), 153.1 (Cq триазол), 155.3 (Cq триазол), 171.8 (CO Aib).δ (ppm) 23.5 (CH ₃ Aib), 23.7 (CH ₃ Aib), 29.6 (CH ₂ βTrp), 30.3 (

-benzyl and CH ₂ -

-indole), 44.1 (

-CH ₂ -indole), 46.1 (СН αTrp), 56.8 (Cq Aib), 109.8 (С ₃ Trp), 109.9 (С ₃ indole), 111.9 (С ₇ indole and С ₇ Trp), 118.3 (С ₄ Trp) , 118.4 (C ₄ indole), 118.9 (C ₅ indole and C ₅ Trp), 121.3 (C ₆ Trp), 121.5 (C ₆ indole), 123.7 (C ₂ indole), 124.7 (C ₂ Trp), 127.0 (C ₉ indole), 127.2 _(C2 and _C6 benzyl), 127.4 _(C9 Trp), 128.8 _(C3 and _C5 benzyl), 129.0 _(C4 benzyl), 136.3 _(C1 benzyl), 136.4 _(C8 indole and C ₈ Trp), 153.1 (Cq triazole), 155.3 (Cq triazole), 171.8 (CO Aib).

(S) -N- (1- (4- (2,4-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 112):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.26 (3H, s, CH ₃ Aib), 1.29 (3H, s, CH ₃ Aib), 3.24 (1 H, dd, J = 14 Hz and 6 Hz, CH ₂ βTrp), 3.33 (1 H , dd, J = 14 Hz and 9 Hz, CH ₂ βTrp), 3.64 (3H, s, OCH ₃ ), 3.68 (3H, s, OCH ₃ ), 3.99 (2H, s, CH ₂ phenyl), 4.84 (1 H, d, J = 17 Hz, CH ₂ -o, para-dimethoxybenzyl), 5.05 (1H, d, J = 17 Hz, CH ₂ -o, para-dimethoxybenzyl), 5.13 (1 H, m, CH αTrp) , 6.24 (2H, m, H ₅ and H ₆ about, para-dimethoxybenzyl), 6.52 (1 H, d, J _m = 2 Hz, H ₃ about, para-dimethoxybenzyl), 6.83 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 7.01 (1 H, t, J ₀ = 8 Hz, H ₆ Trp), 7.04 (1 H, s, H ₂ Trp), 7.05-7.23 (6H, m, H ₄ Trp and CH-phenyl), 7.27 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 8.01 (3H, brs, NH ₂ Aib), 8.90 (1 H, d, J = 8 Hz, NH amide), 10.77 (1 H, d, J = 2 Hz, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.6 (CH ₃ Aib), 29.1 (CH ₂ βTrp), 30.6 (CH ₂ -phenyl), 41.9 (CH ₂ -o, para-dimethoxybenzyl), 45.7 (CH αTrp), 55.7 (OCH ₃ ), 55.9 (OCH ₃ ), 56.7 (Cq Aib), 99.9 (C ₃ o, para-dimethoxybenzyl), 105.1 (C ₅ o, para-dimethoxybenzyl), 109.9 (C ₃ Trp), 111.7 (C ₇ Trp), 115.5 ( C, o, p-dimethoxybenzyl), 118.3 (C ₄ Trp), 118.6 (C ₅ Trp), 121.3 (C ₆ Trp), 124.2 (C ₂ Trp), 127.0 (C ₆ o, p-dimethoxybenzyl), 127.3 ( C ₉ Trp), 127.8 (C ₄ phenyl), 128.8 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 136.2 (C ₈ Trp), 136.4 (C ₁ phenyl), 153.9 (Cq triazole), 155.5 ( Cq triazole), 157.6 (C ₂ about, para-dimethoxybenzyl), 160.8 (C4 about, para-dimethoxybenzyl), 171.8 (CO amide).

(R) -N- (1- (4- (3,5-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 113):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.32 (2Н, m, СН₂ βTrp), 3.61 (6Н, s, ОСН₃), 5.02 (2Н, m, СН₂-мета-диметоксибензил), 5.18 (1 Н, m, CH αTrp), 6.07 (2Н, d, J_m=2 Hz, Н₂ и Н₆ мета-диметоксибензил), 6.42 (1 Н, brs, Н₄ мета-диметоксибензил), 6.83 (1 Н, t, J₀=7 Hz, Н₅ Trp), 6.99 (1 Н, t, J₀=8 Hz, H₆ Trp), 7.08 (1H, d, J=2 Hz, H₂ Trp), 7.13 (3H, t, J₀=8 Hz, H₃, H₄ и H₅ фенил), 7.20 (3Н, d, J₀=7 Hz, H₂ и H₆ фенил, H₄ Trp), 7.28 (1H, d, J₀=8 Hz, H₇ Trp), 7.99 (3H, brs, NH₂ Aib), 8.92 (1 H, d, J=8 Hz, NH амид), 10.77 (1 H, s, NH индол).δ (ppm) 1.24 (3H, s, CH ₃ Aib), 1.27 (3H, s, CH ₃ Aib), 2.83 (4H, s,

-

phenyl), 3.32 (2H, m, CH ₂ βTrp), 3.61 (6H, s, OCH ₃ ), 5.02 (2H, m, CH ₂ metha-dimethoxybenzyl), 5.18 (1 H, m, CH αTrp), 6.07 (2H, d, J _m = 2 Hz, H ₂ and H ₆ meta-dimethoxybenzyl), 6.42 (1 N, brs, H ₄ meta-dimethoxybenzyl), 6.83 (1 N, t, J ₀ = 7 Hz, N ₅ Trp), 6.99 (1 H, t, J ₀ = 8 Hz, H ₆ Trp), 7.08 (1H, d, J = 2 Hz, H ₂ Trp), 7.13 (3H, t, J ₀ = 8 Hz, H ₃ , H ₄ and H ₅ phenyl), 7.20 (3H, d, J ₀ = 7 Hz, H ₂ and H ₆ phenyl, H ₄ Trp), 7.28 (1H, d, J ₀ = 8 Hz, H ₇ Trp ), 7.99 (3H, brs, NH ₂ Aib), 8.92 (1 H, d, J = 8 Hz, NH amide), 10.77 (1 H, s, NH indole).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 29.2 (CH₂ βTrp), 32.7 (СН₂-

-фенил), 45.6 (CH αTrp), 45.8 (СН₂-мета-диметоксибензил), 55.6 (OCH₃), 56.8 (Cq Aib), 99.6 (C₄ мета-диметоксибензил), 104.6 (C₂ и C₆ мета-диметоксибензил), 109.9 (C₃Trp), 111.8 (C₇Trp), 118.2 (C₄Trp), 118.7(C₅ Trp), 121.3 (C₆Trp), 124.8 (C₂Trp), 126.5 (C₄ фенил), 127.3 (C₉ Trp), 128.7 (C₂, C₃, С₅ и С₆ фенил), 136.4 (C₈ Trp), 138.6 (C₄ мета-диметоксибензил), 140.9(0, фенил), 154.6 (Cq триазол), 154.8 (Cq триазол), 161.4 (C₃ и C₅ мета-диметоксибензил), 171.8 (CO амид).δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.5 (

-CH ₂ -phenyl), 29.2 (CH ₂ βTrp), 32.7 (CH ₂ -

phenyl), 45.6 (CH αTrp), 45.8 (CH ₂ metha-dimethoxybenzyl), 55.6 (OCH ₃ ), 56.8 (Cq Aib), 99.6 (C ₄ meta-dimethoxybenzyl), 104.6 (C ₂ and C ₆ meta dimethoxybenzyl), 109.9 (C ₃ Trp), 111.8 (C ₇ Trp), 118.2 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.8 (C ₂ Trp), 126.5 (C ₄ phenyl ), 127.3 (C ₉ Trp), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 136.4 (C ₈ Trp), 138.6 (C ₄ meta-dimethoxybenzyl), 140.9 (0, phenyl), 154.6 ( Cq triazole), 154.8 (Cq triazole), 161.4 (C ₃ and C ₅ meta-dimethoxybenzyl), 171.8 (CO amide).

(R) -N- (1- (4- (4-bromobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 114):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.23 (3H, s, CH ₃ Aib), 1.25 (3H, s, CH ₃ Aib), 3.26 (1 H, dd, ³ J = 14 Hz and 6 Hz, CH ₂ Trp), 3.34 (1 H, dd, ³ J = 14 Hz and 9 Hz, CH ₂ βTrp), 4.01 (2H, m, СН ₂ -benzyl), 5.01 (1 H, m, СН αTrp), 5.08 (2H, s, СН ₂ - para-bromobenzyl), 6.59 (2H, d, J ₀ = 8 Hz, H ₂ and H ₆ para-bromobenzyl), 6.81 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 6.94 (1 H, s, H ₂ Trp), 6.98 (1H, t, J ₀ = 7 Hz, H ₆ Trp), 7.06 (2H, m, H ₂ and H ₆ benzyl), 7.12 (1 H, d, J ₀ = 7 Hz , H ₄ Trp), 7.16-7.20 (3H, m, H ₃ , H ₄ and H ₅ benzyl), 7.26 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 7.29 (2H, d, J ₀ = 8 Hz, H ₃ and H ₅ benzyl), 8.00 (3H, brs, NH ₂ Aib), 8.92 (1H, d, J = 8 Hz, NH amide), 10.78 (1H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-парабромобензил), 45.7 (CH αTrp), 56.7 (Cq Aib), 109.7 (C₃ Trp), 111.8 (C₇ Trp), 118.2 (C₄ триптофан), 118.7 (C₅ Trp), 121.2 (C₄ пара-бромобензил),121.3 (C₆ Trp), 124.9 (C₂ триптофан), 127.0 (C₂ и C₆ бензил), 127.2 (C₉ Trp),128.3 (C₂ и C₆ пара-бромобензил), 128.9 (C₃, C₄ и C₅ бензил), 131.9 (C₃ и C₅ пара-бромобензил), 135.2 (C₁ пара-бромобензил), 136.2 (C₈ Trp), 136.4 (C₁ бензил), 153.9 (Cq триазол), 155,3 (Cq триазол), 171.9 (CO Aib).δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 29.0 (CH ₂ βTrp), 30.5 (CH ₂ -benzyl), 45.6 (

-parabromobenzyl), 45.7 (CH αTrp), 56.7 (Cq Aib), 109.7 (C ₃ Trp), 111.8 (C ₇ Trp), 118.2 (C ₄ tryptophan), 118.7 (C ₅ Trp), 121.2 (C ₄ para- bromobenzyl), 121.3 (C ₆ Trp), 124.9 (C ₂ tryptophan), 127.0 (C ₂ and C ₆ benzyl), 127.2 (C ₉ Trp), 128.3 (C ₂ and C ₆ para-bromobenzyl), 128.9 (C ₃ , C ₄ and C ₅ benzyl), 131.9 (C ₃ and C ₅ para-bromobenzyl), 135.2 (C ₁ para-bromobenzyl), 136.2 (C ₈ Trp), 136.4 (C ₁ benzyl), 153.9 (Cq triazole), 155.3 (Cq triazole), 171.9 (CO Aib).

(R) -N- (1- (4- (2-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 115):

¹ H NMR (300 MHz, DMSO-d ⁶ , 300K):

δ (ppm) 1.24 (3H, s, CH ₃ Aib), 1.27 (3H, s, CH ₃ Aib), 3.20 (1 H, dd, J = 14 Hz and 5 Hz, CH ₂ βTrp), 3.33 (1 H , dd, J = 14 Hz and 9 Hz, CH ₂ βTrp), 3.68 (3H, s, OCH ₃ ), 4.00 (2H, s, CH ₂ phenyl), 4.95 (1H, d, J = 17 Hz, CH _2- O-methoxybenzyl), 5.07 (1 H, m, CH αTrp), 5.18 (1 H, d, J = 17 Hz, CH ₂ -O-methoxybenzyl). 6.27 (1 H, d, J ₀ = 8 Hz, H ₃ o-methoxybenzyl), 6.67 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 6.77 (1 H, t, J ₀ = 6 Hz , H ₆ Trp), 6.92-7.05 (6H, m, H ₂ Trp, H ₂ and H ₆ phenyl, H ₄ , H ₅ and H ₆ o-methoxybenzyl), 7.14-7.26 (5H, m, H ₄ and H ₇ Trp, H ₃ , H ₄ and H ₅ phenyl), 8.03 (3H, brs, NH ₂ Aib), 8.91 (1 H, d, J = 8 Hz, NH amide), 10.78 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.5 (CH ₃ Aib), 23.6 (CH ₃ Aib), 29.1 (CH ₂ βTrp), 30.5 ( C H ₂ -phenyl), 42.1 (CH ₂ -omethoxybenzyl), 45.7 (CH αTrp), 55.9 (OCH ₃ ), 56.7 (Cq Aib), 109.8 (C ₃ Trp), 111.3 (C ₃ o-methoxybenzyl), 111.7 (C ₇ Trp), 118.2 (C ₄ Trp), 118.7 (C ₅ Trp), 120.9 (C ₅ O-methoxybenzyl), 121.2 (C ₆ Trp), 123.3 (C ₁ o-methoxybenzyl), 124.8 (C ₂ Trp), 126.6 (C ₂ and C ₆ phenyl), 127.1 (C ₄ o-methoxybenzyl), 127.2 (C ₉ Trp), 128.8 (C ₃ , C ₄ and C ₅ phenyl), 129.5 (C ₆ o-methoxybenzyl), 136.0 (C ₁ phenyl), 136.4 (C ₈ Trp), 154.0 (Cq triazole), 155.6 (Cq triazole), 156.5 (C ₂ o-methoxybenzyl), 171.8 (CO Aib).

(S) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 116):

¹ H NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.30 (2H, t, CH₂ βTrp), 3.61 (3H, s, OCH₃), 3.69 (3H, s, OCH₃), 4.87 (1 H, d, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.03 (1 H, d, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.20 (1H, m, СН αTrp), 6.29 (1 H, dd, J₀=8 Hz и J_m=2 Hz, H₅ о,пара-диметоксибензил), 6.43 (1H, d, J₀=8 Hz, H₆ о,пара-диметоксибензил), 6.55(1 H,d, J_m=2Hz, H₃о,пара-диметоксибензил), 6.83 (1 H, t, J₀=8 Hz, H₅ Trp), 6.99 (1 H, t, J₀=8 Hz, H₆ Trp), 7.06 (1H, d, J=2 Hz, H₂ Trp), 7.09-7.25 (6H, m, H₄ Trp и CHar фенил), 7.28 (1H, d, J₀=8 Hz, H₇ Trp), 8.04 (3H, brs, NH₂ Aib), 8.92 (1H, d, J=8 Hz, NH амид), 10.79 (1 H, s, NH индол Trp).δ (ppm) 1.28 (3H, s, CH ₃ Aib), 1.32 (3H, s, CH ₃ Aib), 2.81 (4H, m,

-

phenyl), 3.30 (2H, t, CH ₂ βTrp), 3.61 (3H, s, OCH ₃ ), 3.69 (3H, s, OCH ₃ ), 4.87 (1 H, d, J = 17 Hz, CH ₂ - o, para-dimethoxybenzyl), 5.03 (1 H, d, J = 17 Hz, СН ₂ , para-dimethoxybenzyl), 5.20 (1H, m, СН αTrp), 6.29 (1 H, dd, J ₀ = 8 Hz and J _m = 2 Hz, H _{5 °} , para-dimethoxybenzyl), 6.43 (1H, d, J ₀ = 8 Hz, H _{6 °} , para-dimethoxybenzyl), 6.55 (1 H, d, J _m = 2Hz, H ₃ о, para-dimethoxybenzyl), 6.83 (1 H, t, J ₀ = 8 Hz, H ₅ Trp), 6.99 (1 H, t, J ₀ = 8 Hz, H ₆ Trp), 7.06 (1H, d , J = 2 Hz, H ₂ Trp), 7.09-7.25 (6H, m, H ₄ Trp and CHar phenyl), 7.28 (1H, d, J ₀ = 8 Hz, H ₇ Trp), 8.04 (3H, brs, NH ₂ Aib), 8.92 (1H, d, J = 8 Hz, NH amide), 10.79 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-CН₂-фенил), 29.1 (CH₂ βTrp), 32.7 (СН₂-

-фенил), 41.8 (СН₂-о,пара-диметоксибензил), 45.7 (CH αTrp), 55.7 (OCH₃), 55.9 (OCH₃), 56.8 (Cq Aib), 99.1 (C₃ о,пара-диметоксибензил), 105.2 (C₅ о,пара-диметоксибензил), 109.9 (C₃ Trp), 111.8 (C₇ Trp), 115.6 (C₁ о,пара-диметоксибензил), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.4 (C₂Trp), 126.6 (C₄ фенил), 127.3 (C₉ Trp), 128.2 (C₆ о,пара-диметоксибензил), 128.7 (C₂, C₃, C₅ и C₆ фенил), 136.4 (C₈ Trp), 140.9 (С₁ фенил), 154.6 (Cq триазол), 155.0 (Cq триазол), 157.8 (C₂ о,пара-диметоксибензил), 160.9 (C₄ о,пара-диметоксибензил), 171.8 (CO Aib).δ (ppm) 23.6 (CH ₃ Aib), 23.7 (CH ₃ Aib), 26.5 (

-CH ₂ phenyl), 29.1 (CH ₂ βTrp), 32.7 (CH ₂ -

phenyl), 41.8 (CH ₂ -o, para-dimethoxybenzyl), 45.7 (CH αTrp), 55.7 (OCH ₃ ), 55.9 (OCH ₃ ), 56.8 (Cq Aib), 99.1 (C ₃ about, para-dimethoxybenzyl) , 105.2 (C ₅ about, para-dimethoxybenzyl), 109.9 (C ₃ Trp), 111.8 (C ₇ Trp), 115.6 (C ₁ about, para-dimethoxybenzyl), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp) , 121.3 (C ₆ Trp), 124.4 (C ₂ Trp), 126.6 (C ₄ phenyl), 127.3 (C ₉ Trp), 128.2 (C ₆ about, para-dimethoxybenzyl), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 136.4 (C ₈ Trp), 140.9 (C ₁ phenyl), 154.6 (Cq triazole), 155.0 (Cq triazole), 157.8 (C ₂ about, para-dimethoxybenzyl), 160.9 (C ₄ about, couple -dimethoxybenzyl), 171.8 (CO Aib).

(R) -N- (1- (4,5-diphenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2 methylpropanamide (Compound 117):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 2.83 (2H, t, J=8 Hz, N-СН₂-

-фенил), 3.38 (2H, m, N-

-СН₂-фенил), 3.84 (1H, m, СН₂ βTrp), 3.94 (1H, m, CH₂ βTrp), 5.23 (1H, m, CH αTrp), 6.84 (2H, m, H₄ фенил из С-СН₂-СН₂-фенил и Н₄ фенил из N-СН₂-СН₂-фенил), 6.93 (1Н, t, J₀=8 Hz, Н₅ Trp), 7.00 (1Н, 1, J₀=8 Hz, H₆ Trp), 7.07 (1H, d, J=2 Hz, H₂ Trp), 7.11-7.27 (9H, m, H₂, H₃, H₅ и H₆ фенил из С-СН₂-СН₂-фенил, H₂, Н₃, Н₅ и Н₆ фенил из N-CH₂-CH₂-фeнил и Н₄ Trp), 7.50 (1Н, d, J₀=8 Hz, Н₇ Trp), 8.07 (3Н, brs, NH₂ Aib), 9.04 (1 H, d, J=8 Hz, NH амид), 10.85 (1H, s, NH индол Trp).δ (ppm) 1.32 (3H, s, CH ₃ Aib), 1.37 (3H, s, CH ₃ Aib), 2.59 (4H, m, C-

-

phenyl), 2.83 (2H, t, J = 8 Hz, N-CH ₂ -

phenyl), 3.38 (2H, m, N-

-CH ₂ -phenyl), 3.84 (1H, m, CH ₂ βTrp), 3.94 (1H, m, CH ₂ βTrp), 5.23 (1H, m, CH αTrp), 6.84 (2H, m, H ₄ phenyl from С -CH ₂ -CH ₂ phenyl and H ₄ phenyl from N-CH ₂ -CH ₂ phenyl), 6.93 (1H, t, J ₀ = 8 Hz, H ₅ Trp), 7.00 (1H, 1, J ₀ = 8 Hz, H ₆ Trp), 7.07 (1H, d, J = 2 Hz, H ₂ Trp), 7.11-7.27 (9H, m, H ₂ , H ₃ , H ₅ and H ₆ phenyl from C-CH ₂ - CH ₂ phenyl, H ₂ , H ₃ , H ₅ and H ₆ phenyl from N-CH ₂ -CH ₂ phenyl and H ₄ Trp), 7.50 (1H, d, J ₀ = 8 Hz, H ₇ Trp), 8.07 (3H, brs, NH ₂ Aib), 9.04 (1 H, d, J = 8 Hz, NH amide), 10.85 (1H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 29.5 (CH₂ βTrp), 32.4 (С-СН₂-

-фенил), 35.8 N-СН₂-

-фенил), 44.2 (N-

-СН₂-фенил), 45.9 (СН αTrp), 56.8 (Cq Aib), 109.7 (С₃ Trp), 111.9 (С₇ Trp), 118.4 (С₄ Trp), 118.9 (С₅ Trp), 121.4 (С₆ Trp), 124.8 (С₂ Trp), 126.6 (С₄ фенил из С-СН₂-СН₂-фенил), 127.2 (С₄ фенил из N-СН₂-СН₂-фенил), 127.4 (С₉ Trp), 128.7 (С₂ и С₆ фенил из С-СН₂-СН₂-фенил, С₂ и С₆ фенил из 1N-СН₂-СН₂-фенил), 128.8 (С₃ и С₅ фенил из С-СН₂-СН₂-фенил, С₃ и С₅ фенил из N-СН₂-СН₂-фенил), 136.5 (С₁ фенил из N-СН₂-СН₂-фенил), 137.5 (С₁ фенил из С-СН₂-СН₂-фенил), 140.8 (С₈ Trp), 154.1 (Cq триазол), 154.7 (Cq триазол), 171.9 (СО Aib).δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 25.9 (C-

-CH ₂ -phenyl), 29.5 (CH ₂ βTrp), 32.4 (С-СН ₂ -

phenyl), 35.8 N-CH ₂ -

phenyl), 44.2 (N-

-CH ₂ -phenyl), 45.9 (СН αTrp), 56.8 (Cq Aib), 109.7 (С ₃ Trp), 111.9 (С ₇ Trp), 118.4 (С ₄ Trp), 118.9 (С ₅ Trp), 121.4 (С ₆ Trp), 124.8 (C ₂ Trp), 126.6 (C ₄ phenyl from C-CH ₂ -CH ₂ phenyl), 127.2 (C ₄ phenyl from N-CH ₂ -CH ₂ phenyl), 127.4 (C ₉ Trp ), 128.7 (C ₂ and C ₆ phenyl from C-CH ₂ -CH ₂ phenyl, C ₂ and C ₆ phenyl from 1N-CH ₂ -CH ₂ phenyl), 128.8 (C ₃ and C ₅ phenyl from C- CH ₂ -CH ₂ phenyl, C ₃ and C ₅ phenyl from N-CH ₂ -CH ₂ phenyl), 136.5 (C ₁ phenyl from N-CH ₂ -CH ₂ phenyl), 137.5 (C ₁ phenyl from C -CH ₂ -CH ₂ -phenyl), 140.8 (C ₈ Trp), 154.1 (Cq triazole), 154.7 (Cq triazole), 171.9 (CO Aib).

(R) -N- (1- (4- (3,4-dichlorobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) - 2-amino-2-methylpropanamide (Compound 118):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.24 (3H, s, CH ₃ Aib), 1.25 (3H, s, CH ₃ Aib), 3.33 (2H, m, CH ₂ βTrp), 4.04 (2H, s, CH ₂ -benzyl), 5.05 (1Н, m, СН αTrp), 5.12 (2Н, s, СН ₂ -meta, para-dichlorobenzyl), 6.49 (1 Н, dd, J ₀ = 8 Hz and J _m = 2 Hz, H ₆ meta, para- dichlorobenzyl), 6.80 (1 H, t, J ₀ = 8 Hz, H ₅ Trp), 6.87 (1H, d, J _m = 2 Hz, H ₂ Trp), 6.98 (1 H, t, J ₀ = 7 Hz , H ₆ Trp), 7.02-7.10 (3H, m, H ₂ and H ₆ benzyl, H ₅ meta, para-dichlorobenzyl), 7.18 (3H, m, H ₃ , H ₄ and H ₅ benzyl), 7.26 (2H , m, H ₄ and H ₇ Trp), 8.04 (3H, brs, NH ₂ Aib), 8.94 (1 H, d, J = 9 Hz, NH amide), 10.81 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-бензил), 45.1(

-мета,пара-дихлоробензил), 45.6 (CH αTrp), 56.7 (Cq Aib), 109.6 (C₃ Trp), 126.4 (С₆ мета,пара-дихлоробензил), 127.0 (С₂ мета,пара-дихлоробензил), 127.2 (С₉ Trp), 128.4 (С₂ и С₆ бензил), 130.7 (С₄ и С₅ мета,пара-дихлоробензил), 131.8 (С₃ мета,пара-дихлоробензил), 136.0 (С₁ бензил), 136.4 (С₈ Trp), 136.7 (С₁ мета,пара-дихлоробензил), 154.1 (Cq триазол), 155.2 (Cq триазол), 172.0 (СО Aib).δ (ppm) 23.4 (CH ₃ Aib), 23.8 (CH ₃ Aib), 29.0 (CH ₂ βTrp), 30.4 (

-benzyl), 45.1 (

metha, para-dichlorobenzyl), 45.6 (CH αTrp), 56.7 (Cq Aib), 109.6 (C ₃ Trp), 126.4 (C ₆ meta, para-dichlorobenzyl), 127.0 (C ₂ meta, para-dichlorobenzyl), 127.2 (C ₉ Trp), 128.4 (C ₂ and C ₆ benzyl), 130.7 (C ₄ and C ₅ meta, para-dichlorobenzyl), 131.8 (C ₃ meta, para-dichlorobenzyl), 136.0 (C ₁ benzyl), 136.4 ( C ₈ Trp), 136.7 (C ₁ meta, para-dichlorobenzyl), 154.1 (Cq triazole), 155.2 (Cq triazole), 172.0 (CO Aib).

(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide ( Compound 120):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.18 (3H, s, CH ₃ Aib), 1.26 (3H, s, CH ₃ Aib), 3.09 (1 H, dd, J = 14 Hz and 6 Hz, CH ₂ βPhe), 3.18 (1H, dd, J = 14 Hz and 9 Hz, CH ₂ βPhe), 3.99 (2H, d, J = 4 Hz, CH ₂ phenyl), 4.95 (1 H, d, J = 16 Hz, CH ₂ para-methoxybenzyl ), 5.06 (1 H, d, J = 16 Hz, CH ₂ -para-methoxybenzyl), 5.13 (1H, m, CH βPhe), 6.78 (4H, s, CHar p-methoxybenzyl), 7.02-7.08 (4H, m, H ₂ and H ₆ phenyl, H ₂ and H ₆ Phe), 7.12-7.25 (6H, m, H ₃ , H ₄ and H ₅ phenyl, H ₃ , H ₄ and H ₅ Phe), 7.99 (3H, brs, NH ₂ Aib), 8.92 (1 H, d, J = 8 Hz, NH amide).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.4 (CH ₃ Aib), 23.8 (CH ₃ Aib), 30.7 (CH ₂ -phenyl), 38.7 (CH ₂ βPhe), 45.9 (CH ₂ -paramethoxybenzyl), 46.4 (CH αPhe), 55.6 (OCH ₃ ), 56.7 (Cq Aib), 114.6 (C ₃ and C ₅ p-methoxybenzyl), 126.9 and 127.1 (C ₄ phenyl and C ₄ Phe), 127.7 (C, p-methoxybenzyl), 128.2 (C ₂ and C ₆ Phe), 128.5 (C ₃ and C ₅ Phe), 128.9 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 129.7 (C ₂ and C ₆ para-methoxybenzyl), 136.3 (C ₁ phenyl), 137.6 (C ₁ Phe), 154.0 (Cq triazole), 154.9 (Cq triazole), 159.2 (C ₄ para-methoxybenzyl), 171.7 (CO amide).

(R) -N- (1- (4- (4-fluorobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 121):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.34 (2Н, m, СН₂ βTrp), 5.06 (2Н, s, СН₂-пара-фторобензил), 5.16 (1 Н, m, CH αTrp), 6.85 (3Н, m, Н₅ Trp, Н₃ и Н₅ пapa-фторобензил), 6.98-7.04 (4Н, m, Н₂ и Н₆ Trp, Н₂ и Н₆ фенил), 7.09-7.11 (2Н, m, Н₂ и Н₆ пapa-фторобензил), 7.15 (1 Н, d, J₀=6 Hz, Н₄ Trp), 7.19 (3Н, t, J₀=8 Hz, H₃, H₄ и H₅ фенил), 7.29 (1 H, d, J₀=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib), 8.94 (1 H, d, J=8 Hz, NH амид), 10.78 (1 H, s, NH индол Trp).δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.28 (3H, s, CH ₃ Aib), 2.82 (4H, m,

-

phenyl), 3.34 (2H, m, CH ₂ βTrp), 5.06 (2H, s, CH ₂ -parafluorobenzyl), 5.16 (1 H, m, CH αTrp), 6.85 (3H, m, H ₅ Trp, H ₃ and H ₅ papa-fluorobenzyl), 6.98-7.04 (4H, m, H ₂ and H ₆ Trp, H ₂ and H ₆ phenyl), 7.09-7.11 (2H, m, H ₂ and H ₆ papa-fluorobenzyl) 7.15 (1 H, d, J ₀ = 6 Hz, H ₄ Trp), 7.19 (3H, t, J ₀ = 8 Hz, H ₃ , H ₄ and H ₅ phenyl), 7.29 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 8.01 (3H, brs, NH ₂ Aib), 8.94 (1 H, d, J = 8 Hz, NH amide), 10.78 (1 H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 29.2 (CH₂ βTrp), 32.7 (СН₂-

-фенил), 45.4 (СН₂-пара-фторобензил), 45.7 (CH αTrp)), 56.8 (Cq Aib), 109.8 (C₃ Trp), 111.8 (C₇ Trp), 115.9 и 116.2 (C₃ и C₅ пара-фторобензил), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.8 (C₂ Trp), 126.5 (C₄ фенил), 127.3 (C₉ Trp), 128.5 (C₂ и C₆ пара-фторобензил), 128.7 (C₂, C₃, C₅ и C₆ фенил), 132.2 (С₁ пара-фторобензил), 136.4 (C₈Trp), 140.9 (С, фенил), 154.5 (Cq триазол), 154.7 (Cq триазол), 160.3 (С₄ пара-фторобензил), 171.9 (СО амид).δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.5 (

-CH ₂ -phenyl), 29.2 (CH ₂ βTrp), 32.7 (CH ₂ -

phenyl), 45.4 (CH ₂ -para-fluorobenzyl), 45.7 (CH αTrp)), 56.8 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 115.9 and 116.2 (C ₃ and C ₅ para-fluorobenzyl), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.8 (C ₂ Trp), 126.5 (C ₄ phenyl), 127.3 (C ₉ Trp), 128.5 (C ₂ and C ₆ para-fluorobenzyl), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 132.2 (C ₁ para-fluorobenzyl), 136.4 (C ₈ Trp), 140.9 (C, phenyl), 154.5 ( Cq triazole), 154.7 (Cq triazole), 160.3 (C ₄ para-fluorobenzyl), 171.9 (CO amide).

NMR ¹⁹ F (282 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) -114.9 (1F, m, para-fluorobenzyl).

(R) -N- (1 - (4- (3,4-dichlorobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 122):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.34 (2Н, d, J=7 Hz, СН₂ βTrp), 5.1 1 (3Н, m, CH αTrp) и СН₂-мета,пара-дихлоробензил), 6.63 (1Н, dd, J₀=8 Hz и J_m=2 Hz, H₆ мета,пара-дихлоробензил), 6.83 (1 H, t, J₀=8 Hz, H₅Trp), 6.99 (1 H, t, J₀=8 Hz, H₆ Trp), 7.05 (1 H, d, J=2 Hz, H₂ Trp), 7.12 (5H, m, СНаr фенил), 7.17 (1 H, d, J₀=8 Hz, H₄Trp), 7.21 (1 H, s, H₂ мета,пара-дихлоробензил), 7.27 (1 H, d, J₀=8 Hz, H₅ мета,пара-дихлоробензил), 7.39 (1H, d, J₀=8 Hz, H₇Trp), 8.02 (3H, brs, NH₂ Aib), 8.94 (1 H, d, J=8 Hz, NH амид), 10.78 (1 H, s, NH индол Trp).δ (ppm) 1.25 (3H, s, CH ₃ Aib), 1.26 (3H, s, CH ₃ Aib), 2.84 (4H, m,

-

-phenyl), 3.34 (2Н, d, J = 7 Hz, СН ₂ βTrp), 5.1 1 (3Н, m, CH αTrp) and СН ₂ -meta, para-dichlorobenzyl), 6.63 (1Н, dd, J ₀ = 8 Hz and J _m = 2 Hz, H ₆ meta, para-dichlorobenzyl), 6.83 (1 H, t, J ₀ = 8 Hz, H ₅ Trp), 6.99 (1 H, t, J ₀ = 8 Hz, H ₆ Trp), 7.05 (1 H, d, J = 2 Hz, H ₂ Trp), 7.12 (5H, m, CH-phenyl), 7.17 (1 H, d, J ₀ = 8 Hz, H ₄ Trp), 7.21 (1 H, s, H ₂ meta, para-dichlorobenzyl), 7.27 (1 H, d, J ₀ = 8 Hz, H ₅ meta, para-dichlorobenzyl), 7.39 (1H, d, J ₀ = 8 Hz, H ₇ Trp), 8.02 (3H, brs, NH ₂ Aib), 8.94 (1 H, d, J = 8 Hz, NH amide), 10.78 (1 H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-фенил), 29.1 (CH₂ βTrp), 32.6 (

-СН₂-фенил), 44.7 (СН₂-мета,пара-дихлоробензил), 45.6 (CH αTrp),56.6 (CqAib), 109.7 (C₃ Trp), 111.8 (C₇ Trp), 118.1 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.9 (C₂ Trp), 126.5 (C₄ фенил и C₆ мета,пара-дихлоробензил), 127.2 (C₉ Trp), 128.7 (C₂, C₃, C₅ и C₆ фенил, C₂ мета,пара-дихлоробензил), 130.9 (C₄ мета,пара-дихлоробензил), 131.4 (C₅ мета,пара-дихлоробензил), 132.0 (C₃ мета,пара-дихлоробензил), 136.4 (C₈ Trp), 137.2 (C₁ мета,пара-дихлоробензил), 140.8 (С₁ фенил), 154.5 (Cq триазол), 154.7 (Cq триазол), 171.9 (CO амид).δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.4 (CH ₂ -

phenyl), 29.1 (CH ₂ βTrp), 32.6 (

-CH ₂ -phenyl), 44.7 (CH ₂ -metha, para-dichlorobenzyl), 45.6 (CH αTrp), 56.6 (CqAib), 109.7 (C ₃ Trp), 111.8 (C ₇ Trp), 118.1 (C ₄ Trp) , 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.9 (C ₂ Trp), 126.5 (C ₄ phenyl and C ₆ meta, para-dichlorobenzyl), 127.2 (C ₉ Trp), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ phenyl, C ₂ meta, para-dichlorobenzyl), 130.9 (C ₄ meta, para-dichlorobenzyl), 131.4 (C ₅ meta, para-dichlorobenzyl), 132.0 (C ₃ meta, para-dichlorobenzyl) 136.4 (C ₈ Trp), 137.2 (C ₁ meta, para-dichlorobenzyl), 140.8 (C ₁ phenyl), 154.5 (Cq triazole), 154.7 (Cq triazole), 171.9 (CO amide).

(R) -N- (1- (4- (4-methylbenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 124):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 1.22 (3Н, s, СН ₃ Aib), 1.27 (3Н, s, СН ₃ Aib), 2.22 (3Н, s, СН ₃ para-methylbenzyl), 3.22 (1 Н, dd, J = 14 Hz and 6 Hz, CH ₂ βTrp), 3.33 (1 H, dd, J = 14 Hz and 9 Hz, CH ₂ βTrp), 3.99 (2H, s, CH ₂ benzyl), 5.04 (2H, s, CH ₂ - para-methylbenzyl), 5.09 (1H, m, CH αTrp), 6.64 (2H, d, J ₀ = 8 Hz, H ₃ and H ₅ para-methylbenzyl), 6.78 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 6.98 (4H, t, J ₀ = 7 Hz, H ₆ Trp, H ₃ , H ₄ and H ₅ benzyl), 7.01 (1 H, d, J = 2 Hz, H ₂ Trp), 7.07 (2H, d, J ₀ = 7 Hz, H ₂ and H ₆ para-methylbenzyl), 7.20 (3H, m, H ₄ Trp, H ₂ and H ₆ benzyl), 7.26 (1H, d, J ₀ = 8 Hz , H ₇ Trp), 7.98 (3H, brs, NH ₂ Aib), 8.89 (1H, d. J = 8 Hz, NH amide), 10.74 (1 H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 21.0 (CH ₃ para-methylbenzyl), 23.5 (CH ₃ Aib), 23.7 (CH ₃ Aib), 29.1 (CH ₂ βTrp), 30.6 (CH ₂ -benzyl), 45.7 (CH αTrp), 46.0 ( CH ₂ -para-methylbenzyl), 56.7 (Cq Aib), 109.8 (C ₃ Trp), 111.7 (C ₇ Trp), 118.3 (C ₄ Trp), 118.6 (C ₅ Trp), 121.2 (C ₆ Trp), 124.8 (C ₂ Trp), 126.3 (C ₃ and C ₅ para-methylbenzyl), 127.0 (C ₄ benzyl), 127.2 (C ₉ Trp), 128.9 (C ₂ , C ₃ , C ₅ and C ₆ benzyl), 129.7 ( C ₂ and C ₆ para-methylbenzyl), 132.9 (C ₁ para-methylbenzyl), 136.3 (C ₄ para-methylbenzyl), 136.4 (C ₈ Trp), 137.4 (C ₁ benzyl), 153.9 (Cq triazole), 155.3 ( Cq triazole), 171.8 (CO amide).

(S) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-2-methylpropanamide (Compound 125):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 2.52 (4Н, t, J=7 Hz,

-СН₂-

-фенил), 3.35 (2Н, d, J=7 Hz, CH₂ βTrp), 3.68 (3Н, s, ОСН₃), 4.98 (2Н, s, СН₂-пара-метоксибензил), 5.20 (1 Н, m, СН αTrp), 6.75 (4Н, s, СНаr пара-метоксибензил), 6.83 (1 Н, t, J₀=8 Hz, Н₅ Trp), 6.99 (1 Н, t, J₀=7 Hz, H₆ Trp), 7.06 (3H, m, H₂ и H₆ фенил, H₂ Trp), 7.14 (1 H, d, J₀=7 Hz, H₄ Trp), 7.19 (3H, t, J₀=8 Hz, H₃, H₄ и H₅ фенил), 7.29 (1 H, d, J₀=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib), 8.94 (1 H, d, J=8 Hz, NH амид), 10.79 (1 H, d, J=2 Hz, NH индол Trp).δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.31 (3H, s, CH ₃ Aib), 1.74 (2H, m, (CH ₂ -

-CH ₂ -phenyl), 2.52 (4H, t, J = 7 Hz,

-CH ₂ -

phenyl), 3.35 (2H, d, J = 7 Hz, CH ₂ βTrp), 3.68 (3H, s, OCH ₃ ), 4.98 (2H, s, CH ₂ -paramethoxybenzyl), 5.20 (1 N, m , СН αTrp), 6.75 (4Н, s, СНа para-methoxybenzyl), 6.83 (1 Н, t, J ₀ = 8 Hz, Н ₅ Trp), 6.99 (1 Н, t, J ₀ = 7 Hz, H ₆ Trp), 7.06 (3H, m, H ₂ and H ₆ phenyl, H ₂ Trp), 7.14 (1 H, d, J ₀ = 7 Hz, H ₄ Trp), 7.19 (3H, t, J ₀ = 8 Hz , H ₃ , H ₄ and H ₅ phenyl), 7.29 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 8.01 (3H, brs, NH ₂ Aib), 8.94 (1 H, d, J = 8 Hz, NH amide), 10.79 (1 H, d, J = 2 Hz, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 28.5 (

-СН₂-СН₂-фенил), 29.2 (СН₂ βTrр), 34.7 (СН₂-СН₂-

-фенил), 45.5 (СН₂-пара-метоксибензил), 45.8 (CH αTrp), 55.5 (ОСН₃), 56.8 (Cq Aib), 109.8 (С₃ Trp), 111.8 (С₇ Trp), 114.6 (С₃ и С₅ пара-метоксибензил), 118.3 (С₄ Trp), 118.7 (С₅Trp), 121.3 (С₆ Trp), 124.9 (С₂ Trp), 126.2 (С₄ фенил), 127.3 (С₉ Trp), 127.8 (С₁ пара-метоксибензил), 127.9 (С₃, С₄ и С₅ фенил), 128.7 (С₂ и С₆ пара-метоксибензил), 136.4 (С₈ Trp), 141.7 (С₁ фенил), 154.7 (Cq триазол), 154.8 (Cq триазол), 159.2 (С₁ пара-метоксибензил), 171.9 (СО амид).δ (ppm) 23.6 (CH ₃ Aib), 23.8 (CH ₃ Aib), 24.1 (CH ₂ -

-CH ₂ -phenyl), 28.5 (

-CH ₂ -CH ₂ -phenyl), 29.2 (CH ₂ βTrp), 34.7 (CH ₂ -CH ₂ -

phenyl), 45.5 (CH ₂ -paramethoxybenzyl), 45.8 (CH αTrp), 55.5 (OCH ₃ ), 56.8 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 114.6 (C ₃ and C ₅ para-methoxybenzyl), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.9 (C ₂ Trp), 126.2 (C ₄ phenyl), 127.3 (C ₉ Trp), 127.8 (C ₁ para-methoxybenzyl), 127.9 (C ₃ , C ₄ and C ₅ phenyl), 128.7 (C ₂ and C ₆ para-methoxybenzyl), 136.4 (C ₈ Trp), 141.7 (C ₁ phenyl), 154.7 ( Cq triazole), 154.8 (Cq triazole), 159.2 (C ₁ para-methoxybenzyl), 171.9 (CO amide).

(S) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 126):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300K):

δ (ppm) 1.25 (3Н, s, СН ₃ Aib), 1.28 (3Н, s, СН ₃ Aib), 3.26 (1 Н, dd, J = 14 Hz and 6 Hz, СН ₂ βTrp), 3.34 (1 Н , dd, J = 14 Hz and 8 Hz, CH ₂ βTrp), 3.99 (2H, s, СН ₂ -phenyl), 4.98 (2H, s, СН ₂ -para-methoxybenzyl), 5.13 (1 H, m, CH αTrp)), 6.68 (4H, s, СНа para-methoxybenzyl), 6.80 (1 H, t, J ₀ = 8 Hz, H ₅ Trp), 6.99 (1H, t, J ₀ = 8 Hz, H ₆ Trp) 7.02-7.06 (4H, m, H ₂ and H ₄ Trp, H ₂ and H ₆ phenyl), 7.20 (3H, m, H ₃ , H ₄ and H ₅ phenyl), 7.27 (1H, d, J ₀ = 8 Hz, H ₇ Trp), 8.00 (3H, s, NH ₂ Aib), 8.91 (1 H, d, J = 8 Hz, NH amide), 10.76 (1H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

δ (ppm) 23.5 (CH ₃ Aib), 23.7 (CH ₃ Aib), 29.1 (CH ₂ βTrp), 30.6 ( С Н ₂ -phenyl), 45.7 (CH αTrp and С Н ₂ -paramethoxybenzyl), 55.5 ( OCH ₃ ), 56.7 (Cq Aib), 109.8 (C ₃ Trp), 111.7 (C ₇ Trp), 114.5 (C ₃ and C ₅ para-methoxybenzyl), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.8 (C ₂ Trp), 127.1 (C ₄ phenyl), 127.3 (C ₉ Trp), 127.6 (C ₁ para-methoxybenzyl), 127.8 (C ₂ and C ₆ para-methoxybenzyl), 128.8 (C ₂ and C ₆ phenyl), 128.9 (C ₃ and C ₅ phenyl), 136.3 (C ₈ Trp), 136.4 (C ₁ phenyl), 153.8 (Cq triazole), 155.2 (Cq triazole), 159.2 (C ₄ pair -methoxybenzyl), 171.9 (СО amide).

N - ((R) -1- (4- (4-nitrobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 128):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.28 (1 Н, dd, ³J=14 Hz и 8 Hz, CH₂ βTrp), 3.43 (1 H, dd, ³J=14 Hz и 7 Hz, CH₂ βTrp), 5.05 (1 H, m, СН αTrp), 5.25 (2H, d, J=7 Hz, СН₂-пара-нитробензил), 6.72 (1H, 1, J₀=7 Hz, H₅ Trp), 6.89 (2H, d, J₀=9 Hz, H₂ и H₆ пара-нитробензил), 6.92 (1H, t, J₀=7 Hz, H₆ Trp), 7.00 (1 H, d, J_m=2 Hz, H₂ Trp), 7.08-7.15 (4H, m, H₄ и H₇ Trp, H₂ и H₆ фенил), 7.17 (2H, J₀=7 Hz, H₃ и H₅ фенил), 7.24 (1 H, t, J₀=8 Hz, H₄ фенил), 7.92 (2H, d, J₀=9 Hz, H₃ и H₅ пара-нитробензил), 8.06 (3Н, brs, NH₂ Aib), 8.98 (1 H, d, J=8 Hz, NH амид), 10.79 (1 H, s, NH индол Trp).δ (ppm) 1.28 (3H, s, CH ₃ Aib), 1.29 (3H, s, CH ₃ Aib), 2.77-2.94 (4H, m,

-

phenyl), 3.28 (1 H, dd, ³ J = 14 Hz and 8 Hz, CH ₂ βTrp), 3.43 (1 H, dd, ³ J = 14 Hz and 7 Hz, CH ₂ βTrp), 5.05 (1 H , m, СН αTrp), 5.25 (2H, d, J = 7 Hz, СН ₂ -para-nitrobenzyl), 6.72 (1H, 1, J ₀ = 7 Hz, H ₅ Trp), 6.89 (2H, d, J ₀ = 9 Hz, H ₂ and H ₆ para-nitrobenzyl), 6.92 (1H, t, J ₀ = 7 Hz, H ₆ Trp), 7.00 (1 H, d, J _m = 2 Hz, H ₂ Trp), 7.08-7.15 (4H, m, H ₄ and H ₇ Trp, H ₂ and H ₆ phenyl), 7.17 (2H, J ₀ = 7 Hz, H ₃ and H ₅ phenyl), 7.24 (1 H, t, J ₀ = 8 Hz, H ₄ phenyl), 7.92 (2H, d, J ₀ = 9 Hz, H ₃ and H ₅ para-nitrobenzyl), 8.06 (3H, brs, NH ₂ Aib), 8.98 (1 H, d, J = 8 Hz, NH amide), 10.79 (1 H, s, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-фенил), 45.3 (

-пара-нитробензил), 45.7 (CH αTrp), 56.8 (Cq Aib), 109.6 (C₃ Trp), 111.8(C₇ Trp), 118.1 (C₄ Trp), 118.5 (C₅ Trp), 121.2 (C₆ Trp), 124.1 (С₂ и С₅ пара-нитробензил), 124.8 (C₂ Trp), 126.5 (C₂ и C₅ фенил), 127.2 (C₉ Trp, С₁ и C₆ пара-нитробензил), 128.7 (C₃, C₄ и C₅ фенил), 136.4 (C₈ Trp), 140.8 (С₁ фенил), 143.5 (С₁ пара-нитробензил), 154.5 (Cq триазол), 154.8 (Cq триазол), 172.0 (CO Aib).δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.4 ( C H ₂ -CH ₂ phenyl), 29.1 (CH ₂ βTrp), 32.6 (CH ₂ -

phenyl), 45.3 (

-para-nitrobenzyl), 45.7 (CH αTrp), 56.8 (Cq Aib), 109.6 (C ₃ Trp), 111.8 (C ₇ Trp), 118.1 (C ₄ Trp), 118.5 (C ₅ Trp), 121.2 (C ₆ Trp), 124.1 (C ₂ and C ₅ para-nitrobenzyl), 124.8 (C ₂ Trp), 126.5 (C ₂ and C ₅ phenyl), 127.2 (C ₉ Trp, C ₁ and C ₆ para-nitrobenzyl), 128.7 ( C ₃ , C ₄ and C ₅ phenyl), 136.4 (C ₈ Trp), 140.8 (C ₁ phenyl), 143.5 (C ₁ para-nitrobenzyl), 154.5 (Cq triazole), 154.8 (Cq triazole), 172.0 (CO Aib )

(S) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 129):

¹ H NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.34 (2H, d, J=7 Hz, CH₂ βTrp), 3.68 (3H, s, OCH₃), 4.99 (2H, s,

-пара-метоксибензил), 5.20 (1 H, m, CH αTrp), 6.75 (4H, m, СНаr пара-метоксибензил), 6.83 (1 H, t, J₀=7 Hz, H₅ Trp), 7.03 (1H, t, J₀=8 Hz, H₆ Trp), 7.04 (1 H, d, J=2 Hz, H₂ Trp), 7.10 (2H, d, J₀=7 Hz, H₂ и H₆ фенил), 7.13 (1H, d, J₀=8 Hz, H₄ Trp), 7.19 (3H, t, J₀=7 Hz, H₃, H₄ и H₅ фенил), 7.29 (1 H, d, J₀=8 Hz, H₇ Trp), 8.01 (3H, brs, NH₂ Aib), 8.94 (1 H, d, J=8 Hz, NH амид), 10.78 (1 H, d, J=2 Hz, NH индол Trp).δ (ppm) 1.27 (3H, s, CH ₃ Aib), 1.30 (3H, s, CH ₃ Aib), 2.81 (4H, m,

-

phenyl), 3.34 (2H, d, J = 7 Hz, CH ₂ βTrp), 3.68 (3H, s, OCH ₃ ), 4.99 (2H, s,

-para-methoxybenzyl), 5.20 (1 H, m, CH αTrp), 6.75 (4H, m, CHа-para-methoxybenzyl), 6.83 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 7.03 (1H , t, J ₀ = 8 Hz, H ₆ Trp), 7.04 (1 H, d, J = 2 Hz, H ₂ Trp), 7.10 (2H, d, J ₀ = 7 Hz, H ₂ and H ₆ phenyl) , 7.13 (1H, d, J ₀ = 8 Hz, H ₄ Trp), 7.19 (3H, t, J ₀ = 7 Hz, H ₃ , H ₄ and H ₅ phenyl), 7.29 (1 H, d, J ₀ = 8 Hz, H ₇ Trp), 8.01 (3H, brs, NH ₂ Aib), 8.94 (1 H, d, J = 8 Hz, NH amide), 10.78 (1 H, d, J = 2 Hz, NH indole Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 29.2 (CH₂ βTrp), 32.7 (СН₂-

-фенил), 45.3 (

-пара-метоксибензил), 45.7 (CH αTrp), 55.5 (OCH₃), 56.8 (Cq Aib), 109.9 (C₃ Trp), 111.8 (C₇ Trp), 114.6 (C₃ и C₅ пара-метоксибензил), 118.3 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆Trp), 124.8 (C₂ Trp), 126.5 (C₄ фенил), 127.3 (C₉ Trp и С₁ пара-метоксибензил), 127.9 (C₂ и C₆ пара-метоксибензил), 128.7 (C₂, C₃, C₅ и C₆ пара-метоксибензил), 136.5 (C₈ Trp), 140.9 (С₁ фенил), 154.4 (Cq триазол), 154.7 (Cq триазол), 159.2 (C₄ пара-метоксибензил), 171.9 (CO амид).δ (ppm) 23.6 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.6 (

-CH ₂ -phenyl), 29.2 (CH ₂ βTrp), 32.7 (CH ₂ -

phenyl), 45.3 (

-para-methoxybenzyl), 45.7 (CH αTrp), 55.5 (OCH ₃ ), 56.8 (Cq Aib), 109.9 (C ₃ Trp), 111.8 (C ₇ Trp), 114.6 (C ₃ and C ₅ para-methoxybenzyl), 118.3 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.8 (C ₂ Trp), 126.5 (C ₄ phenyl), 127.3 (C ₉ Trp and C ₁ para-methoxybenzyl), 127.9 ( C ₂ and C ₆ para-methoxybenzyl), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ para-methoxybenzyl), 136.5 (C ₈ Trp), 140.9 (C ₁ phenyl), 154.4 (Cq triazole), 154.7 ( Cq triazole), 159.2 (C ₄ para-methoxybenzyl), 171.9 (CO amide).

(R) -N- (1- (4- (4-methoxyphenethyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 130):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-фенил и СН₂-

-пара-метоксибензил), 2.83 (2Н, t, J=8 Hz, СН₂-

-фенил), 3.37 (2Н, m,

-СН₂-пара-метоксибензил), 3.65 (3Н, s, ОСН₃), 3.77 (1 Н, m, СН₂ βTrp), 3.89 (1 Н, m, СН₂ βTrp), 5.20 (1 Н, m, СН αTrp), 6.72 (4Н, s, СНar пара-метоксибензил), 6.94 (1 Н, t, J₀=7 Hz, Н₅ Trp), 7.02 (1 Н, t, J₀=8 Hz, H₆ Trp), 7.05 (1H, d, J=2 Hz, H₂ Trp), 7.11 (2H, d, J₀=7 Hz, H₂ и H₆ фенил), 7.16 (1 H, d, J₀=7 Hz, H₄ Trp), 7.25 (3H m, H₃, H₄, H₅ фенил), 7.50 (1H, d, J₀=8 Hz, H₇ Trp), 8.05 (3H, brs, NH₂ Aib), 9.02 (1 H, d, J=8 hz, NH амид), 10.83 (1 H, d, J=2 Hz, NH индол Trp).δ (ppm) 1.30 (3H, s, CH ₃ Aib), 1.35 (3H, s, CH ₃ Aib), 2.55 (4H, m, CH ₂ -

phenyl and CH ₂ -

-para-methoxybenzyl), 2.83 (2H, t, J = 8 Hz, CH ₂ -

-phenyl) 3.37 (2H, m,

-CH ₂ -para-methoxybenzyl), 3.65 (3Н, s, OCH ₃ ), 3.77 (1 Н, m, СН ₂ βTrp), 3.89 (1 Н, m, СН ₂ βTrp), 5.20 (1 Н, m, СН αTrp), 6.72 (4Н, s, СНar para-methoxybenzyl), 6.94 (1 Н, t, J ₀ = 7 Hz, Н ₅ Trp), 7.02 (1 Н, t, J ₀ = 8 Hz, H ₆ Trp ), 7.05 (1H, d, J = 2 Hz, H ₂ Trp), 7.11 (2H, d, J ₀ = 7 Hz, H ₂ and H ₆ phenyl), 7.16 (1 H, d, J ₀ = 7 Hz , H ₄ Trp), 7.25 (3H m, H ₃ , H ₄ , H ₅ phenyl), 7.50 (1H, d, J ₀ = 8 Hz, H ₇ Trp), 8.05 (3H, brs, NH ₂ Aib), 9.02 (1 H, d, J = 8 hz, NH amide); 10.83 (1 H, d, J = 2 Hz, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 29.5 (CH₂ βTrp), 32.5 (СН₂-

-фенил), 35.0 (СН₂-CH₂-пара-метоксибензил), 44.4 (СН₂-CH₂-пара-метоксибензил), 45.8 (СН αTrp), 55.4 (OCH₃), 56.8 (Cq Aib), 109.9 (C₃ Trp), 111.9 (C₇ Trp), 114.2 (C₃ и C₅ пара-метоксибензил), 118.4 (C₄ Trp), 118.9 (C₅ Trp), 121.4 (C₆Trp), 124.7 (C₂ Trp), 126.5 (C₄ фенил), 127.4 (C₉ Trp), 128.7 (C₂, C₃, C₅ и C₆ фенил), 129.4 (С₁ пара-метоксибензил), 130.3 (C₂ и C₆ пара-метоксибензил), 136.5 (C₈ Trp), 141.0 (C₁ фенил), 154.0 (Cq триазол), 154.5 (Cq триазол), 158.6 (C₄ пара-метоксибензил), 171.8 (CO амид).δ (ppm) 23.5 (CH ₃ Aib), 23.8 (CH ₃ Aib), 26.0 (

-CH ₂ -phenyl), 29.5 (CH ₂ βTrp), 32.5 (CH ₂ -

-phenyl), 35.0 (CH ₂ - C H ₂ -para-methoxybenzyl), 44.4 ( C H ₂ -CH ₂ -para-methoxybenzyl), 45.8 (CH αTrp), 55.4 (OCH ₃ ), 56.8 (Cq Aib), 109.9 (C ₃ Trp), 111.9 (C ₇ Trp), 114.2 (C ₃ and C ₅ para-methoxybenzyl), 118.4 (C ₄ Trp), 118.9 (C ₅ Trp), 121.4 (C ₆ Trp), 124.7 (C ₂ Trp), 126.5 (C ₄ phenyl), 127.4 (C ₉ Trp), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 129.4 (C ₁ para-methoxybenzyl), 130.3 (C ₂ and C ₆ para-methoxybenzyl), 136.5 (C ₈ Trp), 141.0 (C ₁ phenyl), 154.0 (Cq triazole), 154.5 (Cq triazole), 158.6 (C ₄ para-methoxybenzyl), 171.8 (CO amide).

(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 132):

¹ N NMR (300 MHz, DMSO-d ⁶ , 300 K):

-

-фенил), 3.40 (2H, m, CH₂ βTrp), 5.26 (1 H, m, СН αTrp), 5.37 (2H, s, СН₂-о-пиридил), 6.83 (1 H, t, J₀=7 Hz, H₅ Trp), 6.98 (1H, t, J₀=8 Hz, H₆ Trp), 7.11-7.30 (10H, m, H₂, H₄ и H₇ Trp, СНаr фенил, H₃ и H₅ о-пиридил), 7.71 (1 H, t, J₀=7 Hz, H₄ о-пиридил), 8.22 (3Н, brs, NH₂ Aib), 8.42 (1 H, d, Jαβ=4 Hz, H₆ о-пиридил), 9.05 (1 H, d, J=8 Hz, NH амид), 10.87 (1 H, s, NH индол Trp).δ (ppm) 1.26 (3H, s, CH ₃ Aib), 1.29 (3H, s, CH ₃ Aib), 2.95 (4H, m,

-

phenyl), 3.40 (2H, m, CH ₂ βTrp), 5.26 (1 H, m, CH αTrp), 5.37 (2H, s, CH ₂ -o-pyridyl), 6.83 (1 H, t, J ₀ = 7 Hz, H ₅ Trp), 6.98 (1H, t, J ₀ = 8 Hz, H ₆ Trp), 7.11-7.30 (10H, m, H ₂ , H ₄ and H ₇ Trp, CH-phenyl, H ₃ and H ₅ o-pyridyl), 7.71 (1 H, t, J ₀ = 7 Hz, H ₄ o-pyridyl), 8.22 (3H, brs, NH ₂ Aib), 8.42 (1 H, d, Jαβ = 4 Hz, H ₆ o-pyridyl), 9.05 (1 H, d, J = 8 Hz, NH amide), 10.87 (1 H, s, NH indol Trp).

¹³ C NMR (75 MHz, DMSO-d ⁶ , 300 K):

-СН₂-фенил), 28.6 (CH₂ βTrp), 32.5 (СН₂-

-фенил), 45.7 (СН αTrp), 47.6 (CH₂ о-пиридил), 56.8 (Cq Aib), 109.8 (C₃Trp), 111.8 (C₇ Trp), 118.3 (C₄ Trp), 118.6 (C₅ Trp), 121.2 (C₆ Trp), 122.0 (C₃ о-пиридил), 123.6 (C₅ о-пиридил), 126.3 (C₂ Trp), 126.6 (C₄ фенил), 127.3 (C₉ Trp), 128.7 (C₂, C₃, C₅ и C₆ фенил), 136.4 (C₈ триптофан), 137.7 (C₄ о-пиридил), 140.7 (С₁ фенил), 150.1 (C₆ о-пиридил), 154.9 (Cq триазол), 155.2 (Cq триазол), 158.7 (C₂ о-пиридил), 172.0 (CO амид).δ (ppm) 23.4 (CH ₃ Aib), 23.7 (CH ₃ Aib), 26.4 (

-CH ₂ -phenyl), 28.6 (CH ₂ βTrp), 32.5 (CH ₂ -

phenyl), 45.7 (CH αTrp), 47.6 (CH ₂ o-pyridyl), 56.8 (Cq Aib), 109.8 (C ₃ Trp), 111.8 (C ₇ Trp), 118.3 (C ₄ Trp), 118.6 (C ₅ Trp), 121.2 (C ₆ Trp), 122.0 (C ₃ o-pyridyl), 123.6 (C ₅ o-pyridyl), 126.3 (C ₂ Trp), 126.6 (C ₄ phenyl), 127.3 (C ₉ Trp), 128.7 (C ₂ , C ₃ , C ₅ and C ₆ phenyl), 136.4 (C ₈ tryptophan), 137.7 (C ₄ o-pyridyl), 140.7 (C ₁ phenyl), 150.1 (C ₆ o-pyridyl), 154.9 (Cq triazole), 155.2 (Cq triazole), 158.7 (C ₂ o-pyridyl), 172.0 (CO amide).

N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 179):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-фенил), 3.29 (t, 2Н, J=8 Hz, СН₂ βTrp), 3.61 (s, 3Н, OCH₃), 3.68 (s, 3Н, ОСН₃), 4.85 (d, 1 Н, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.02 (d, 1 Н, J=17 Hz, СН₂-о,пара-диметоксибензил), 5.18 (m, 1H, CH аTrp), 6.29 (dd, 1H, J₀=8 Hz и J_m=2 Hz, H₅ о,пара-диметоксибензил), 6.40 (d, 1 H, J₀=8 Hz, H₆ о,пара-диметоксибензил), 6.55 (d, 1H, J_m=2 Hz, H₃ о,пара-диметоксибензил), 6.82 (t, 1H, J₀=8 Hz, H₅ Trp), 6.99 (t, 1 H, J₀=8 Hz, H₆ Trp), 7.05 (s, 1H, H₂ Trp), 7.09-7.24 (m, 6H, H₄ Trp и СНаr фенил), 7.27 (d, 1 H, J₀=8 Hz, H₇ Trp), 7.99 (s, 3Н, большой, NH₂ Aib TFA соль), 8.89 (d, 1 H, J=8 Hz, NH амид), 10.77 (s, 1H, NH индол Trp).δ (ppm) 1.26 (s, 3H, CH ₃ Aib), 1.30 (s, 3H, CH ₃ Aib), 2.82 (m, 4H,

-

phenyl), 3.29 (t, 2H, J = 8 Hz, CH ₂ βTrp), 3.61 (s, 3H, OCH ₃ ), 3.68 (s, 3H, OCH ₃ ), 4.85 (d, 1 H, J = 17 Hz, СН ₂ -о, para-dimethoxybenzyl), 5.02 (d, 1 Н, J = 17 Hz, СН ₂ -о, para-dimethoxybenzyl), 5.18 (m, 1H, CH аTrp), 6.29 (dd, 1H, J ₀ = 8 Hz and J _m = 2 Hz, H ₅ about, para-dimethoxybenzyl), 6.40 (d, 1 H, J ₀ = 8 Hz, H ₆ about, para-dimethoxybenzyl), 6.55 (d, 1H, J _m = 2 Hz, H ₃ about, para-dimethoxybenzyl), 6.82 (t, 1H, J ₀ = 8 Hz, H ₅ Trp), 6.99 (t, 1 H, J ₀ = 8 Hz, H ₆ Trp), 7.05 (s, 1H, H ₂ Trp), 7.09-7.24 (m, 6H, H ₄ Trp and CH-phenyl), 7.27 (d, 1 H, J ₀ = 8 Hz, H ₇ Trp), 7.99 (s, 3H, large, NH ₂ Aib TFA salt), 8.89 (d, 1 H, J = 8 Hz, NH amide), 10.77 (s, 1H, NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-СН₂-фенил), 29.2 (CH₂ βTrp), 32.7 (СН₂-

-фенил), 41.6 (СН₂-о,пара-диметоксибензил), 45.7 (CH αTrp), 55.7 (ОСН₃), 55.9 (ОСН₃), 56.7 (Cq Aib), 99.1 (С₃ о,пара-диметоксибензил), 105.2 (С₅ о,пара-диметоксибензил). 110.0 (С₃ Trp), 111.8 (С₇ Trp), 115.7 (С₁ о,пара-диметоксибензил), 118.3 (С₄ Trp), 118.7 (С₅ Trp), 121.3 (С₆ Trp), 126.5 (С₂ Trp и С₆ о,пара-диметоксибензил), 127.3 (С₉ Trp), 128.1 (С₄ фенил), 128.7 (С₂, С₃, С₅ и С₆ фенил), 136.4 (С₈ Trp), 140.9 (С₁ фенил), 154.5 (Cq триазол), 155.0 (Cq триазол), 157.8 (С₂ о,пара-диметоксибензил), 160.9 (С₄ о,пара-диметоксибензил), 171.7 (СО амид).δ (ppm) 23.6 (CH ₃ Aib), 23.7 (CH ₃ Aib), 26.5 (

-CH ₂ -phenyl), 29.2 (CH ₂ βTrp), 32.7 (CH ₂ -

phenyl), 41.6 (CH ₂ -o, para-dimethoxybenzyl), 45.7 (CH αTrp), 55.7 (OCH ₃ ), 55.9 (OCH ₃ ), 56.7 (Cq Aib), 99.1 (C ₃ o, para-dimethoxybenzyl) 105.2 (C ₅ o, para-dimethoxybenzyl). 110.0 (С ₃ Trp), 111.8 (С ₇ Trp), 115.7 (С ₁ о, para-dimethoxybenzyl), 118.3 (С ₄ Trp), 118.7 (С ₅ Trp), 121.3 (С ₆ Trp), 126.5 (С ₂ Trp and С ₆ о, para-dimethoxybenzyl), 127.3 (С ₉ Trp), 128.1 (С ₄ phenyl), 128.7 (С ₂ , С ₃ , С ₅ and С ₆ phenyl), 136.4 (С ₈ Trp), 140.9 ( С ₁ phenyl), 154.5 (Cq triazole), 155.0 (Cq triazole), 157.8 (С ₂ о, para-dimethoxybenzyl), 160.9 (С ₄ о, para-dimethoxybenzyl), 171.7 (СО amide).

N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) Tetrahydro-2H-pyran-4-carboxamide (Compound 184):

¹ N NMR (300 MHz, DMSO d ⁶ , 300 K):

-

-фенил), 3.16 (m, 2Н, Н₂ и Н₆ тетрагидропиран), 3.31 (dd, 1 Н, J=14 Hz и 8 Hz, СН₂ βTrp), 3.35 (dd, 1Н, J=14 Hz и 7 Hz, СН₂ βTrp), 3.66 (s, 3Н, ОСН₃), 3.72 (m, 2Н, Н₂ и Н₆ тетрагидропиран), 5.08 (m, 2Н, СН₂-пара-метоксибензил), 5.26 (m, 1 Н, CH αTrp), 6.73 (s, 4Н, СНаr пара-метоксибензил), 6.87 (t, 1 Н, J₀=8 Hz, Н₅ Trp), 7.02 (m, 2Н, Н₂ и Н₆ Trp), 7.07 (d, 2Н, J₀=7 Hz, Н₂ и Н₆ фенил), 7.18 (m, 3Н, Н₃, Н₄ и Н₅ фенил), 7.30 (m, 2Н, Н₄ и Н₇ Trp), 8.52 (d, 1 Н, J=8 Hz, NH амид), 10.77 (s, 1Н, NH индол Trp).δ (ppm) 1.20 (m, 1 H, H ₅ tetrahydropyran), 1.30 (m, 3H, H ₃ and H ₅ tetrahydropyran), 2.17 (m, 1 H, H ₄ tetrahydropyran), 2.82 (m, 4H,

-

phenyl), 3.16 (m, 2H, H ₂ and H ₆ tetrahydropyran), 3.31 (dd, 1 H, J = 14 Hz and 8 Hz, CH ₂ βTrp), 3.35 (dd, 1H, J = 14 Hz and 7 Hz, CH ₂ βTrp), 3.66 (s, 3H, OCH ₃ ), 3.72 (m, 2H, H ₂ and H ₆ tetrahydropyran), 5.08 (m, 2H, CH ₂ -paramethoxybenzyl), 5.26 (m, 1 H, CH αTrp), 6.73 (s, 4H, СНаpara-methoxybenzyl), 6.87 (t, 1 Н, J ₀ = 8 Hz, Н ₅ Trp), 7.02 (m, 2Н, Н ₂ and Н ₆ Trp), 7.07 (d, 2H, J ₀ = 7 Hz, H ₂ and H ₆ phenyl), 7.18 (m, 3H, H ₃ , H ₄ and H ₅ phenyl), 7.30 (m, 2H, H ₄ and H ₇ Trp) 8.52 (d, 1 H, J = 8 Hz, NH amide); 10.77 (s, 1H, NH indol Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

-СН₂-фенил), 28.8 (C₃ и C₅ тетрагидропиран), 29.2 (CH₂ βTrp), 32.2 (СН₂-

-фенил), 40.7 (C₄ тетрагидропиран), 44.8 (CH αTrp), 45.9 (СН₂-пара-метоксибензил), 55.5 (OCH₃), 66.6 (C₂ и C₆ тетрагидропиран), 109.8 (C₃ Trp), 111.7 (C₇ Trp), 114.5 (C₃ и C₅ пара-метоксибензил), 118.4 (C₄ Trp), 118.7 (C₅ Trp), 121.3 (C₆ Trp), 124.5 (C₂ Trp), 126.7 (C₄ фенил), 127.2 (C₉ Trp), 127.5 (С₁ пара-метоксибензил), 128.8 (C₂ и C₆ фенил), 128.7 (C₃ и C₅ фенил), 127.9 (C₂ и C₆ пара-метоксибензил), 136.4 (C₈ Trp), 140.4 (С₁ фенил), 154.7 (Cq триазол), 155.7 (Cq триазол), 159.2 (C₄ пара-метоксибензил), 174.2 (CO амид).δ (ppm) 26.3 (

-CH ₂ -phenyl), 28.8 (C ₃ and C ₅ tetrahydropyran), 29.2 (CH ₂ βTrp), 32.2 (CH ₂ -

phenyl), 40.7 (C ₄ tetrahydropyran), 44.8 (CH αTrp), 45.9 (CH ₂ para-methoxybenzyl), 55.5 (OCH ₃ ), 66.6 (C ₂ and C ₆ tetrahydropyran), 109.8 (C ₃ Trp), 111.7 (C ₇ Trp), 114.5 (C ₃ and C ₅ para-methoxybenzyl), 118.4 (C ₄ Trp), 118.7 (C ₅ Trp), 121.3 (C ₆ Trp), 124.5 (C ₂ Trp), 126.7 (C ₄ phenyl), 127.2 (C ₉ Trp), 127.5 (C ₁ para-methoxybenzyl), 128.8 (C ₂ and C ₆ phenyl), 128.7 (C ₃ and C ₅ phenyl), 127.9 (C ₂ and C ₆ para-methoxybenzyl ), 136.4 (C ₈ Trp), 140.4 (C ₁ phenyl), 154.7 (Cq triazole), 155.7 (Cq triazole), 159.2 (C ₄ para-methoxybenzyl), 174.2 (CO amide).

N - ((R) -1- (5 - ((1H-indol-3-yl) methyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 185):

¹ H NMR (300 MHz, DMSO d ⁶ , 300 K):

-индол), 5.06 (m, 1 H, CH αTrp), 5.14 (m, 2H, СН₂-мета-метоксибензил), 6.31 (s, 1 H, H₂ мета-метоксибензил), 6.32 (d, 1 H, J₀=7 Hz, H₆ мета-метоксибензил), 6.77 (m, 3Н, H₅ индол, H₅ Trp и H₄ мета-метоксибензил), 6.92 (m, 2H, Н₆ индол и H₆ Trp), 7.02 (m, 2H, H₂ индол и Н₂ Trp), 7.26-7.30 (m, 3Н, Н₅ мета-метоксибензил, Н₄ и Н₇ индол, Н₄ Trp), 7.41 (d, 1 Н, J₀=8 Hz, Н₇ Trp), 7.94 (brs, 3Н, NH₂ Aib TFA соль), 8.87 (d, 1 H, J=8 Hz, NH амид), 10.73 (d, 1 H, J=2 Hz, NH индол), 10.85 (s, 1 H, NH индол Trp).δ (ppm) 1.19 (s, 3H, CH ₃ Aib), 1.23 (s, 3H, CH ₃ Aib), 3.14 (dd, 1H, J = 14 Hz and 5 Hz, CH ₂ βTrp), 3.34 (dd, 1 H, J = 14 Hz and 9 Hz, CH ₂ βTrp), 3.46 (s, 3H, OCH ₃ ), 3.72 (m, 2H,

-indole), 5.06 (m, 1 H, CH αTrp), 5.14 (m, 2H, СН ₂ -meta-methoxybenzyl), 6.31 (s, 1 H, H ₂ meta-methoxybenzyl), 6.32 (d, 1 H, J ₀ = 7 Hz, H ₆ meta-methoxybenzyl), 6.77 (m, 3H, H ₅ indole, H ₅ Trp and H ₄ meta-methoxybenzyl), 6.92 (m, 2H, H ₆ indole and H ₆ Trp), 7.02 (m, 2H, H ₂ indole and H ₂ Trp), 7.26-7.30 (m, 3H, H ₅ meta-methoxybenzyl, H ₄ and H ₇ indole, H ₄ Trp), 7.41 (d, 1 H, J ₀ = 8 Hz, H ₇ Trp), 7.94 (brs, 3H, NH ₂ Aib TFA salt), 8.87 (d, 1 H, J = 8 Hz, NH amide), 10.73 (d, 1 H, J = 2 Hz, NH indole), 10.85 (s, 1 H, NH indole Trp).

¹³ C NMR (75 MHz, DMSO d ⁶ , 300 K):

δ (ppm) 21.7 (CH ₂ -indole), 23.5 (CH ₃ Aib), 23.7 (CH ₃ Aib), 28.9 (CH ₂ βTrp), 45.5 (CH αTrp), 46.2 (CH ₂ -metha-methoxybenzyl), 55.2 (OCH ₃ ), 56.7 (Cq Aib), 108.2 (C ₃ Indole), 109.8 (C ₃ Trp), 111.7 (C ₇ Trp), 111.9 (C ₇ indole and C ₂ meta-methoxybenzyl), 113.7 (C ₄ meta -methoxybenzyl), 118.2 (C ₆ meta-methoxybenzyl), 118.4 (C ₄ Trp), 118.6 (C ₄ indole), 118.9 (C ₅ indole and C ₅ Trp), 121.2 (C ₆ indole), 121.6 (C ₆ Trp ), 127.1 (C ₉ indole), 127.2 (C ₉ Trp), 136.4 (C ₈ Trp), 136.7 (C ₈ indole), 137.5 (C ₁ meta-methoxybenzyl), 154.2 (Cq triazole), 155.3 (Cq triazole) 160.0 (C ₃ meta-methoxybenzyl); 171.8 (CO amide).

II) Analysis of the binding of ligands to GHS-R 1A receptors (membrane preparations from transfected cells LLC PK-1)

A study of the binding / affinity of ligands to GHS-R 1a receptors was carried out in accordance with Guerlavais et al. (J. Med. Chem. 2003, 46: 1191-1203).

LLC PK-1 cell line was originally obtained from pig kidneys (ECACC No. 86121112) (10 μg protein), after which the human GHS-R 1a DNA was transfected briefly (Guerlavais et al., J. Med. Chem. 2003, 46: 1191-1203). Isolated plasma cell membranes of this line were incubated in HB homogenization buffer [50 mM Tris (pH 7.3), 5 mM MgCl ₂ , 2.5 mM EDTA and 30 μg / ml bacitracin (bacitracin, Sigma)] for 60 minutes at 25 ° C (quasistationary conditions) together with 60 pM ¹²⁵ I-His ^9- ghrelin (Amersham) in the presence or absence of competitive inhibitors (compounds of the invention).

The binding affinity for each compound with respect to human GHS-R 1a was measured by determining the displacement of radioactively labeled ghrelin with increasing concentrations of the test compound (from 10 ^-11 to 10 ^-2 M) (each experiment was repeated three times). An excess of (10 ^-6 M) ghrelin was used to determine non-specific binding. The binding reaction was stopped by adding 4 ml of ice-cold HB followed by rapid filtration through Whatman GP / C filters previously soaked in a 0.5% solution of polyethyleneimine to prevent excessive binding of the radioligand to them. The filters were washed three times with 3 ml of ice-cold wash buffer [50 mM Tris (pH 7.3), 10 mM MgCl ₂ , 2.5 mM EDTA and 0.015% (w / v) X-100 Triton], after which the radioactivity bound to the membranes was measured on a gamma counter (Kontron Analytical Gamma Matic, Automatic gamma counting system).

The concentration of test compounds necessary to inhibit the binding of 50% radiolabeled ghrelin (IC ₅₀ ) was determined by processing the obtained competitive binding curves by non-linear regression (PRISM 3.0, Graph Pad San Diego, USA). The following Table 2 presents the results obtained for selected compounds of the invention, compared with examples from the literature. IC ₅₀ values represent the average of at least two independent experiments, each of which was performed in triplicate.

Figure 1-13 shows the measured graphs of competitive binding obtained in the analysis of the binding of the ligand to GHS-R 1A receptors using ¹²⁵ I-His ⁹ -hrelin and selected compounds 9, 31, 39, 45, 50, 62, 64, 71 , 73, 74, 79, 81, and 90.

III) Intracellular analysis of in vitro calcium excretion using CHO cells transfected with the human GHS-R 1a receptor

The potential of the compounds of the invention as modulators of activity of SSHR receptors was measured in an analysis of the release of intracellular calcium using CHO cells transfected with the human GHS-R 1a receptor.

Intracellular calcium release or inhibition was measured using a fluorescent calcium indicator assay (FLIPR) and Fluo-4 AM. CHO cells (CHO-KI Chinese Hamster Ovary cell line (Chinese hamster ovary cell line, ATCC No. CCL-61) were transiently transfected with human GHS-R 1a cDNA by electroporation, after which they were placed in 96-well black-bottom plates (Corning 3603) (80,000 cells / well). Short-term transfection was performed using the Easyject Optima Electroporator (Equibio), according to the manufacturer's instructions. Transfected cells were grown in Eagle Dulbecco-modified medium without phenol red, additionally containing 10% (v / v) non-essential amino acids, 2 nM glutam on penicillin and streptomycin (250 .mu.g / ml-250 u / ml) (all purchased from companies Cambrex) at 37 ° C, 5% CO ₂ in a humidified atmosphere for 24 hours.

After incubation, the transfected cells were washed with 150 μl of Buffer A [Hanks' balanced salt solution (Sigma H-6648), 0.5% (v / v) BSA (Sigma A-7906), 20 mM CaCl ₂ , 2.5 mM probenecid (pH 7.4, dissolved in 1 M NaOH) (Sigma P-8761), and then loaded with a fluorescent calcium indicator Fluo-4 AM (10 ^-6 M) (Interchim UP72972), prepared in Buffer A, additionally containing 0.06% pluronic acid (molecular probes P-6867) (Detergent of soft ionic strength, facilitating loading with Fluo-4AM ether). During this loading, 100 μl of Buffer A with 120 μl / ml pluronic acid and 1 μM Fluo-4AM were added to each well.

After loading Fluo-4AM, transfected cells were incubated for 1 hour in the dark at 37 ° C.

The test compounds in three replicates were dissolved in Buffer A at a concentration of 10 ^-6 M and transferred to another 96-well plate (Fisher Labosi A1210500).

Upon completion of the incubation, excess Fluo-4AM was removed, 100 μl of Buffer A was added to each well at room temperature, after which the buffer was immediately removed by suction. This procedure was repeated, after which 50 μl of Buffer A was added to each well.

Transfected cells were further incubated for 30 minutes at room temperature to ensure complete deesterification of Fluo-4AM esters inside the cell.

Then, both boards — a dark-bottom plate containing transfected cells and a microtiter plate with test compounds — were transferred to a temperature-controlled FlexStation (25 ° C, Benchtop Station Scanning Photometer Flex Station II, Molecular Devices, Sunnyvale, California, USA) for fluorescence measurements.

Since Fluo-4AM allows a large jump in fluorescence intensity upon binding to calcium, the fluorescence value can be used directly as a proportional characteristic of the release of intracellular calcium.

Basic fluorescence of transfected cells was measured for 15 seconds, after which 50 μl of the test compounds were automatically injected into the cells with transfected cells. The fluorescent signal was then recorded for another 45 seconds.

The excitation and emission wavelengths were 485 nm and 525 nm, respectively. The basic fluorescence intensity of Fluo-4AM-loaded transfected cells without test compounds ranged from 800 to 1200 arbitrary units, while the maximum fluorescence of such cells after incubation with the test compounds ranged from 5000 to 7000 arbitrary units and was equivalent to the intensity observed upon stimulation transfected cells with ghrelin dye at a concentration of 10 ^-6 M. For each compound studied, the change in fluorescence upon addition was determined and compared with basal fluorescence measured with a negative control, that is, when only 50 μl of buffer A is added to transfected cells, the ability of the test compounds to induce calcium release and the degree of such release was determined compared to the baseline (0%) and maximum level (100%) achieved with the introduction of 1 μm ghrelin.

For the test compounds identified as agonists of SSHR receptors, EC ₅₀ and K _{i were} determined from dose-response curves. If the compound was identified as an antagonist of SSHR receptors, then IC ₅₀ and K _b (antagonist dissociation constant) were determined using antagonist inhibition curves in the presence of 10 ^-7 M ghrelin (submaximal concentration). IC ₅₀ values are the molar concentration of the CCGR receptor antagonist, which reduces the maximum response when ghrelin is exposed by 50%. The values of K _{b were} determined from the Cheng-Prussoff equation (Lazareno S and Birdsall NJ, Trends Pharmacol SC1. 1993, 14 (6): 237-239).

On Fig-40 shows the calculated dose-response graphs obtained on the basis of in vitro analysis of intracellular calcium release in CHO cells transfected with human GHS-R 1a receptors using selected compounds 1, 9, 12, 20, 22, 31 , 39, 41, 42, 45, 46, 47, 48, 49, 50, 51, 55, 62, 64, 67, 71, 73, 74, 79, 81, 90 and ghrelin, as well as individual EU values of ₅₀ and K _i for agonists and IC ₅₀ and K _b for antagonists.

IV) In vivo plasma GH analysis of male rat pups

Plasma GH concentrations were determined in order to characterize the modulation effect (antagonistic or agonistic) exhibited by the compounds of the present invention, which are ligands of SSHR receptors.

In principle, in vivo analysis of rat plasma GH concentration was carried out in accordance with the work of Torsello et at. (Eur. J. Pharmacol. 1998, 360: 123-129). Sprague-Dawley male rat pups (Charles River, Calco, Italy) were separated from their mothers on the seventh day after birth and evenly randomly assigned to rat rats so that each raised 10 to 12 cubs. On the tenth day, the rat pups were again separated from their mothers. The studied compounds were dissolved in a solvent [DMSO (0.4% of the total volume), distilled water (4% of the total volume), bringing to the required volume was carried out with physiological saline]. One hour after separation from the mothers, the rat pups were injected with isoelectric amounts of the test compounds (160 μg / kg body weight subcutaneously) 10 minutes before the administration of hexarelin (80 μg / kg body weight subcutaneously) or solvent. 15 minutes after this last administration, the rat pups were killed by decapitation. Blood was collected from the main artery, immediately centrifuged, and plasma samples were stored at -20 ° C until the experiment to determine the content of GH.

To determine the plasma concentration of GH, a rat growth hormone immunoassay kit (SPIbio, France, cat. No. 589601) was used in accordance with the manufacturer's instructions. Values are expressed in terms of the NIDDK rat-GH-RP2 standard (activity 2 int / d / mg) in ng / ml plasma. The detection limit, calculated as the concentration leading to 15% replacement of the original label (tracer), was 0.5 ng / ml; intracellular and intercellular coefficients of variation were 4% (n = 24) and 14% (n = 9).

The following table 3 shows the results obtained for selected compounds of the present invention.

Table 3
The relative concentration of GH in plasma after treatment with selected compounds of the invention (160 μg / kg body weight sc) and / or hexarelin (80 μg / kg body weight sc), and / or a solvent Treatment method GH concentration (ng / ml) solvent 4.008 ± 0.469 hexarelin 162.839 ± 21.095 compound 1 there is no data compound 1 + hexarelin 80.22 ± 18.66 compound 12 4.0 ± 0.12 Compound 12 + Hexarelin 200.0 ± 19.7 compound 20 5.27 ± 0.59 compound 20 + hexarelin 220.51 ± 15.52 compound 22 4.88 ± 0.33 compound 22 + hexarelin 239.91 ± 19.75 compound 47 5.658 ± 1.192 Compound 47 + Hexarelin 160.857 ± 13.52 compound 39 5.509 ± 1.950 compound 39 + hexarelin 82.481 ± 11.530 compound 31 119.937 ± 33.054 compound 31 + hexarelin 103.528 ± 14.094 connection 48 6.096 ± 2.091 Compound 48 + Hexarelin 145.946 ± 12.159 compound 44 87.520 ± 15.066 Compound 44 + Hexarelin 100.52 ± 12.112 solvent 2.237 ± 0.073 hexarelin 170.101 ± 13.226 compound 9 13.016 ± 1.960 compound 9 + hexarelin 183.562 ± 16.729 compound 39 5.509 ± 1.95 compound 39 + hexarelin 82.481 ± 11.53 compound 50 9.852 ± 1.040 compound 50 + hexarelin 164.459 ± 4.443 connection 64 13.056 ± 2.169 Compound 64 + Hexarelin 138.394 ± 14.580 solvent 10.729 ± 2.027 hexarelin 253.820 ± 12.268 connection 71 15.326 ± 1.355 compound 71 + hexarelin 173.611 ± 18.444 compound 74 10.571 ± 0.791 compound 74 + hexarelin 194.564 ± 7.658 compound 81 18.634 ± 2.933 compound 81 + hexarelin 216.575 ± 19.734 compound 90 16.857 ± 2.152 Compound 90 + Hexarelin 218.844 ± 19.723

V) Analysis of the eating behavior (food intake) of young male rats

The effect of the compounds of the invention, which are ligands of the SSHR receptor, on eating behavior, that is, on food intake, of young but adult male rats, was analyzed. In general, this analysis was performed in accordance with the work of Torsello et al. (Eur. J. Pharmacol. 1998, 360: 123-129). For analysis, young male Sprague-Dawley rats (Charles River, Calco, Italy) weighing 200-250 g were used. These rats were acclimatized to individual cages and animal room conditions for one week (22 ± 2 ° C, 65% humidity, artificial lighting from 08.00 to 20.00 hours). Over the next week, they were trained daily, simulating the experiment procedure. During this time, rats were given free access to dry food and water. At the end of the training period, the test compounds (160 μg / kg body weight) and / or hexarelin (80 μg / kg body weight) and / or solvent [DMSO (0.4% of the total volume), distilled water (4% of the total volume), bringing to the required volume was carried out with physiological saline].

Hexarelin was used to study the effects of test compounds on stimulated eating behavior. Immediately after the injection, the animals were returned to their cages, where there was a measured amount of standard dry food and an unlimited amount of water. Every hour for the next six hours, the remaining food was carefully collected and weighed, rounded to the nearest 0.1 g. Food consumption was normalized to rat body weight and expressed in grams of food eaten per 100 g of body weight.

The following table 4 shows the results obtained for selected compounds of the invention.

Table 4
Cumulative food intake (g food / 100 g body weight) by young adult male rats 2 hours, 6 hours after treatment with selected compounds of the invention (160 μg / kg body weight sc) and / or hexarelin (80 μg / kg body weight sc ), and / or solvent Treatment method Cumulative food intake (2 hours) Cumulative food intake (over 6 hours) solvent 0.003 ± 0.0015 0.017 ± 0.0026 hexarelin 0.533 ± 0.194 1.0014 ± 0.1973 compound 1 0.02 ± 0.002 0.06 ± 0.03 compound 1 + hexarelin 0.06 ± 0.02 0.33 ± 0.21 compound 12 0.034 ± 0.011 0.06 ± 0.019 Compound 12 + Hexarelin 0.13 ± 0.07 0.48 ± 0.22 compound 20 0.01 0.2 ± 0.19 compound 20 + hexarelin 0.53 ± 0.21 0.63 ± 0.19 compound 22 0.01 0.44 ± 0.2 compound 22 + hexarelin 0.67 ± 0.12 0.86 ± 0.18 compound 47 0.006 ± 0.002 0.02 ± 0 Compound 47 + Hexarelin 0.35 ± 0.201 0.47 ± 0.1943 compound 44 0.43 ± 0.0721 0.7075 ± 0.1471 Compound 44 + Hexarelin 1.2667 ± 0.1319 1.4033 ± 0.1177 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.536 ± 0.176 0.594 ± 0.169 compound 9 0.01 ± 0 0.01 ± 0 compound 9 + hexarelin 0.0104 ± 0.0032 0.0231 ± 0.0032 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 1.060 ± 0.143 1.138 ± 0.114 compound 13 0.057 ± 0.057 0.167 ± 0.167 compound 13 + hexarelin 0.731 ± 0.318 0.792 + 0.337 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 1.060 ± 0.143 1.138 ± 0.114 compound 17 0.001 ± 0.001 0.2661 ± 0.166 Compound 17 + Hexarelin 0.0501 ± 0.049 0.846 ± 0.411 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.428 ± 0.192 0.588 ± 0.303 compound 24 0.008 ± 0.008 0.215 ± 0.200 Compound 24 + Hexarelin 0.586 ± 0.252 0.912 ± 0.359 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.627 ± 0.211 0.778 ± 0.218 compound 30 0.264 ± 0.244 0.277 ± 0.246 Compound 30 + Hexarelin 1.350 ± 0.177 1.449 ± 0.213 solvent 0.184 ± 0.018 0.399 ± 0.201 hexarelin 0.278 ± 0.078 0.883 ± 0.259 compound 38 0.001 ± 0 0.076 ± 0.096 Compound 38 + Hexarelin 0.002 ± 0.002 0.478 ± 0.141 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.26 ± 0.13 0.78 ± 0.25 compound 49 0.004 ± 0.004 0.004 ± 0.004 Compound 49 + Hexarelin 0.057 ± 0.037 0.558 ± 0.212 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.536 ± 0.176 0.594 ± 0.169 compound 50 0.012 ± 0.008 0.039 ± 0.011 compound 50 + hexarelin 0.003 ± 0.002 0.017 ± 0.001 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.427 ± 0.16 0.688 ± 0.203 Treatment method Cumulative food intake (2 hours) Cumulative food intake (over 6 hours) connection 64 0.012 ± 0.008 0.039 ± 0.011 Compound 64 + Hexarelin 0.012 ± 0.004 0.021 ± 0.007 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.696 ± 0.267 0.74 ± 0.27 connection 71 0.522 ± 0.283 0.53 ± 0.28 compound 71 + hexarelin 0.117 ± 0.074 0.20 ± 0.01 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.70 ± 0.116 1.221 ± 0.06 connection 72 0.008 ± 0.003 0.011 ± 0 compound 72 + hexarelin 0.634 ± 0.33 0.746 ± 0.31 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 1.031 ± 0.219 1.455 ± 0.192 connection 80 0.145 ± 0.143 0.346 ± 0.159 Compound 80 + Hexarelin 0.475 ± 0.196 0.733 ± 0.238 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.696 ± 0.267 0.74 ± 0.27 compound 81 0.017 ± 0.004 0.03 ± 0 compound 81 + hexarelin 0.024 ± 0.0101 0.116 ± 0.077 solvent 0.184 ± 0.111 0.497 ± 0.183 hexarelin 0.412 ± 0.173 0.68 ± 0.29 compound 81 0.034 ± 0.003 0.346 ± 0.179 compound 81 + hexarelin 1.4 ± 0.35 1.665 ± 0.345 solvent 0.184 ± 0.111 0.497 + 0.183 hexarelin 0.323 ± 0.131 0.45 ± 0.17 compound 90 0.014 ± 0.001 0.035 ± 0.003 Compound 90 + Hexarelin 0.054 ± 0.041 0.069 ± 0.041

VI) Analysis of binding to motilin receptors (using recombinant HEK-293 cells)

Motilin receptor binding / affinity experiments were performed as described by Feighner SD et al. (Science 1999, 284: 2184-2188). The analysis conditions were as follows:

Source: HEK-293 human recombinant cells [Motilin receptor 1a (MTL-R1a)]

Ligand: 0.1 nM [ ¹²⁵ I] Motilin (human, pig)

Carrier: 1% DMSO

Incubation time / temperature: 2.5 hours at 25 ° C.

Incubation buffer: 50 mM Tris, pH 7.4, 10 mM MgCl ₂ , 0.5% BSA.

Nonspecific ligand: 1 μM motilin (human, pig).

The compounds of the invention were tested at concentrations of 0.01 μM, 0.1 μM, 1 μM and 10 μM.

IC ₅₀ values were determined using non-linear least squares analysis using the Data Analysis Toolbox (MDL Information Systems, USA). The following table 5 presents the results for selected compounds of the invention.

Table 5
The results of the analysis of binding to the motilin receptor (IC ₅₀ values for selected as an example of compounds) No. MTL-R 1A IC ₅₀ [μM] Chemical name 44 1.61 (R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide 64 1.39 (R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide

VII) Investigation of antikachetic effects in adjuvant-induced arthritis models

The effectiveness of the compounds of the invention in the treatment of cachexia was studied by the method of Ibanez de Caceres I et al. (J Endocrinol. 2000, 165 (3): 537-544) using a cachexia model (Roubenoff R et al., Arthritis Rheum. 1997, 40 (3): 534-539).

Table 6 presents the anti-kinetic effect of compound 44 (0.1 μg / kg / day s.c.) in rat models with arthritis, compared with arthritis induced by adjuvant and without treatment.

Table 6
The change in body weight in grams (average for 6 animals in the group) Day 3 Day 6 Day 10 Day 13 Day 15 Day 17 Rats with arthritis caused by adjuvant administration + vehicle -3.02 2.95 11.97 9.32 -2.78 -8.27 Rats with arthritis + compound 44 treatment (0.1 mcg / kg / day s.c.) -5.32 2.98 14.92 08/19 7.05 1.47

VIII) Investigation of the anti-inhibitory effects of isoproterenol-induced lipolysis in adipocyte models

The efficacy of the compounds of the invention as inhibitors of non-acylated ghrelin-induced inhibition of isoproterenol-induced lipolysis has been investigated using an adipocyte model.

Isolation of primary mouse adipocytes

Mice, starting from the age of 4 weeks, were fed for 12 and 18 weeks with a diet rich in fats (60% lipids), inducing obesity in them.

White adipose tissue from epididymal fat was finely triturated and dissolved in a Hepes-based Krebs-Ringer buffer (Krebs-Ringer-Bicarbonate-Hepes (KRBH)) (20 mM Hepes pH 7.4, 120 mM NaCl, 4.7 mM KCl, 1.2 mM K ₂ HPO ₄ , 2.5 mM CaCl ₂ , 1.2 mM MgSO ₄ , 24 mM NaHCO ₃ ) saturated with CO ₂ and containing glucose (1 mg / ml), 1% BSA and collagenase (2 mg / g tissue). Dissolution was carried out with continuous shaking on a shaker (250 rpm) for 45 minutes at 37 ° C.

The cell suspension was filtered through a nylon sieve, separating adipocytes from tissue fragments, and washed three times with 3 ml of warm KRBH 1% BSA.

Cells were resuspended in KRBH 1% BSA and incubated on a shaker (75 rpm) for 30 minutes at 37 ° C.

Lipolysis assay

Primary adipocyte lipolysis was induced by 30 nM isoproterenol in KRBH 4% BSA for 90 minutes with continuous shaking on a shaker (125 rpm) at 37 ° C.

Differentiated cell lipolysis was induced with 30 nM isoproterenol in non-FBS DMEM for 90 minutes with shaking every 15 minutes.

The inhibitory effect of unacylated ghrelin on isoproterenol-induced lipolysis was measured with increasing concentrations of unacylated ghrelin from 10 ^-11 to 10 ^-6 M in the presence or absence of selected compounds of the invention at a concentration of 10 ^-7 M.

The lipolysis index was determined by measuring the release of glycerol after hydrolysis of triglycerides.

The antagonistic effect was determined as follows:

Where

Figures 41-46 show the effects of selected compounds 9, 38, 50, 64, 74, 81 on inhibition curves of isoproterenol-induced lipolysis of unacylated ghrelin in primary adipocytes obtained from obese mice induced by diet.

Claims (22)

1. A method of treating or preventing physiological and / or pathophysiological conditions mediated by growth hormone secretion receptors (SSHR receptors) and selected from the group including growth retardation, cachexia, short, medium and / or long-term energy balance regulation; short-term, medium-term and / or long-term regulation (stimulation and / or inhibition) of food intake; adipogenesis, obesity and / or obesity; an increase and / or decrease in body weight in mammals, which uses a drug containing a pharmacologically effective amount of a compound of formula (I):

where R1 is selected from the group consisting of hydrogen atom, (C1-C12) alkyl phenyl, naphthyl, (C5-C14) phenyl (C1-C12) alkyl, indolylalkyl, which may contain up to 3 substituents independently selected from the group consisting of halogen, -F, -Cl, -Br, -I, -NO ₂ , (C1-C12) alkyl, phenyl, naphthyl, -O- (C1-C12) alkyl;
R2 is selected from the group consisting of (C1-C12) alkyl, phenyl, naphthyl, (C5-C14) phenyl (C1-C12) alkyl, indolylalkyl, which may contain up to 3 substituents independently selected from the group consisting of halogen, -F, -Cl, -Br, -I, -NO ₂ , (C1-C12) alkyl, phenyl, naphthyl, -O- (C1-C12) alkyl;
one of the radicals R3 and R4 represents a hydrogen atom, and the other radical is selected from the group comprising a hydrogen atom, phenyl, naphthyl, indolylalkyl;
R5 is selected from the group consisting of hydrogen atom, phenyl, naphthyl, -CO- (C3-C8) cycloalkyl, -CO-phenyl, -CO- (C5-C7) heteroaryl containing 1, 2 nitrogen atoms, -CO- (C3 -C7) heteroaryl (C1-C4) alkyl containing 1, 2 nitrogen atoms, -CO- (C5-C6) heterocyclyl containing 1, 2 nitrogen or oxygen atoms, -CO-C * (R9R10) -NH ₂ , - CO — CH ₂ —C * (R9R10) —NH ₂ , —CO — C * (R9R10) —CH ₂ —NH ₂ , phenylsulfonyl, which may contain up to 3 substituents independently selected from the group consisting of halogen, —F, - Cl, -Br, -I, -N ₃ , -CN, -NR7R8, -OH, -NO ₂ , (C1-C4) alkyl;
R6 represents a hydrogen atom;
R7 and R8 represent a hydrogen atom;
R9 and R10 are independently selected from the group consisting of a hydrogen atom and (C1-C4) alkyl;
m corresponds to 0, 1 or 2, and preferably 0; and
* means a carbon atom in the R or S configuration, if it is chiral, while the compounds are antagonists of SSHR receptors, and treatment is carried out by modulating SSHR receptors. 2. The method according to claim 1, in which R3 is selected from the group consisting of phenyl, naphthyl, indolylalkyl. 3. The method according to claim 1, in which R4 represents a hydrogen atom;
R5 is selected from the group consisting of hydrogen atom, phenyl, naphthyl, -CO- (C3-C8) cycloalkyl, -CO-phenyl, -CO- (C5-C7) heteroaryl containing 1.2 nitrogen atoms, -CO- (C5 -C7) heteroaryl (C1-C4) alkyl, -CO- (C5-6) heterocyclyl containing 1, 2 nitrogen or oxygen atoms,
moreover, if R5 is —CO- (C5-C7) heteroaryl (C1-C4) alkyl, then heteroaryl is not imidazole;
and, if R5 is —CO- (C5-C6) heterocyclyl, said heterocyclyl contains only nitrogen atoms as heteroatoms, and at least two nitrogen atoms are included in said heterocyclyl;
and where phenyl, naphthyl, - CO- (C3-C8) cycloalkyl, -CO-phenyl, -CO- (C5-C7) heteroaryl, -CO- (C3-C8) heteroaryl (C1-C4) alkyl, -CO- (C5-C6) heterocyclyl may contain up to 3 substituents independently selected from the group consisting of halogen, —F, —Cl, —Br, —I, —N ₃ , —CN, —NR7R8, —OH, —NO ₂ , ( C1-C4) alkyl;
moreover, if R5 is —CO— (C3-C8) cycloalkyl, then R5 is not substituted with NR7R8 at position 1 of cycloalkyl in which the C atom directly bonds (C3-C8) cycloalkyl to the carbonyl group —CO—; and
if R5 is —CO-phenyl and contains only one substituent, then this substituent cannot be —NR7R8;
R6 represents a hydrogen atom;
R7 and R8 represent a hydrogen atom; and
m = 0.1 or 2, more preferably 0. 4. The method according to claim 1, in which R1 is selected from the group comprising hydrogen, methyl, (2-methoxyphenyl) methyl, (3-methoxyphenyl) methyl, (4-methoxyphenyl) methyl, (3-methoxyphenyl) - ethyl, (4-methoxyphenyl) ethyl, phenyl, phenyl methyl, phenyl ethyl, (4-ethyl phenyl) methyl, (4-methyl phenyl) methyl, (4-fluorophenyl) methyl, (4-bromophenyl) - methyl, (2,4-dimethoxyphenyl) methyl, (3,5-dimethoxyphenyl) methyl, 2,2-diphenyl-ethyl, naphthalen-1-yl-methyl, 1H-indol-3-yl-methyl, 2- (1H-indol-3-yl) ethyl, 3- (1H-indol-3-yl) propyl, 4-methyl-phenyl, 4-ethyl-phenyl, n-hexyl, (3,4-dichlorophenyl) - methyl, (4-nitrophenyl) methyl, (pyridin-2-yl) methyl, (pyridin-3- il) methyl, (pyridin-4-yl) methyl, (thiophen-2-yl) methyl, (thiophen-3-yl) methyl, (furan-2-yl) methyl, (furan-3- silt) methyl;
R2 is selected from the group consisting of methyl, 1H-indol-3-yl-methyl, 2- (1H-indol-3-yl) ethyl, 3- (1H-indol-3-yl) propyl, 2-phenyl- ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 2-methoxy-phenylmethyl, 3-methoxy-phenylmethyl, 4-methoxy-phenylmethyl, 2-methoxy-phenylethyl, 3-methoxy-phenylethyl, 4-methoxy-phenylethyl;
R3 is selected from the group consisting of hydrogen, methyl, propan-2-yl, 2-methyl-propan-1-yl, butan-2-yl, butan-1-yl, -CH ₂ -CH, - (CH ₂ ) _2- S-CH ₂ , 1H-indol-3-yl-methyl, phenyl-methyl, 2-phenyl-ethyl, -CH ₂ -O-CH ₂ -phenyl, -CH ₂ -CO-CH ₂ -phenyl, - (CH ₂ ) ₂ -CO-CH ₂ -phenyl, -CH ₂ -C (O) O-phenyl, - (CH ₂ ) ₂ -C (O) O-phenyl, hydroxymethyl, 1-hydroxyethan-1-yl, -CH ₂ -CO-NH ₂ , - (CH ₂ ) ₂ -CO-NH ₂ , (1-hydroxy-benzene-4-yl) methyl, -CH ₂ -CO-OH, - (CH ₂ ) ₂ - CO-OH, - (CH ₂ ) ₄ -NH ₂ , (1H-imidazol-5-yl) methyl, - (CH ₂ ) ₃ -NH-C (NH) -NH ₂ , - (CH ₂ ) ₂ - NH ₂ , - (CH ₂ ) ₃ —NH — CO — NH ₂ , and is preferably selected from the group consisting of 1H-indol-3-yl-methyl, —CH ₂ —CO — CH ₂ phenyl, - (CH ₂ ) -CO-CH ₂ -phenyl, -CH ₂ -C ( O) O-phenyl, - (CH ₂ ) ₂ -C (O) O-phenyl;
R4 represents a hydrogen atom;
R5 is selected from the group consisting of a hydrogen atom, —CO — CH ₂ —NH ₂ (residue Gly), —CO — CH ₂ —CH ₂ —NH ₂ (beta-Ala residue), —CO-CHCH ₃ —NH ₂ (residue D-and / or L-alpha-Ala), -CO- (pyrrolidin-2-yl) (residue D-and / or L-Pro), 2-amino-2-carbonyl-propane (residue 2-amino-isobutyric acids / Alb), 4-carbonyl-1H-piperidine, 3-carbonyl-1H-piperidine, R- (3-carbonyl-1H-piperidine), S- (3-carbonyl-1H-piperidine), 2-carbonyl-1H -piperidine, R- (2-carbonyl-1H-piperidine), S- (2-carbonyl-1H-piperidine), 1-amino-2-carbonyl-benzene, carbonyl-cyclohexane, 2-acetyl-pyridine, 3-acetyl -pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine, 3-propionyl-pyridine, 4-p opionyl pyridine, (R-1-amino) -2-carbonyl-cyclohexane, (S-1-amino) -2-carbonyl-cyclohexane, 2-carbonyl-1H-imidazole, 2-carbonyl-pyridine, 3-carbonyl- pyridine, 4-carbonyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-pyrazine, 2-carbonyl-4-hydroxy-1H-pyrrolidine, 4-carbonyl-1H, 3H-diazacyclohexane, methyl sulfonyl, phenylsulfonyl, 1-carbonyl-1-amino-2-phenylethane, phenylmethyl, 1-carbonyl-4-azide-benzene, 2-carbonyl-2,5-dihydro-1H-pyrrole, 2-carbonyl-piperazine, 2-carbonyl- 1H-pyrrolidine, 2-aminoethane, carbonyl-benzene, 2-carbonyl-pyrazine, 3-carbonyl-pyrazine, 4-carbonyl-oxacyclohexane, 4-methyl-phenylsulfonyl, phenylmethyl-sulfonyl;
R6 represents a hydrogen atom; and
m = 0. 5. The method according to claim 3, in which the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors is carried out by means of a drug obtained from an agonist of SSHR receptors, said treatment or prophylaxis being carried out by modulating SSHR receptors . 6. The method according to claim 4, in which the treatment or prophylaxis of physiological and / or pathophysiological conditions in mammals mediated by SSHR receptors is carried out by means of a drug obtained from an agonist of SSHR receptors, said treatment or prophylaxis being carried out by modulating SSHR receptors . 7. The method according to claim 4, in which R3 is selected from the group consisting of —CH ₂ —CO — CH ₂ phenyl, - (CH ₂ ) ₂ —CO — CH ₂ phenyl, —CH ₂ —CO — NH ₂ , - (CH ₂ ) ₂ —CO — NH ₂ , —CH ₂ —CO — OH, - (CH ₂ ) ₂ —CO — OH, - (CH ₂ ) ₃ —NH — C (NH) —NH ₂ , —CH ₂ -SH, - (CH ₂ ) ₂ -S-CH ₃ . 8. The method according to claim 4, in which R5 is selected from the group comprising a hydrogen atom, methylsulfonyl, phenylsulfonyl, carbonyl-cyclohexane, (R-1-amino) -2-carbonyl-cyclohexane, (S-1-amino) -2 -carbonyl-cyclohexane, 2-carbonyl-pyridine, 3-carbonyl-pyridine, 4-carbonyl-pyridine, 2-acetyl-pyridine, 3-acetyl-pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine, 3-propionyl -pyridine, 4-propionyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-1H-imidazole, 2-carbonyl-pyrazine, 4-carbonyl-1H, 3H-diazacyclohexane. 9. The method according to claim 1, in which the compound is selected from the group including Compound 1
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 2
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 3
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 4
(R) -N- (1- (5-benzyl-4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 5
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 6
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 7
(R) -N- (1- (4- (3-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 8
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 9
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 10
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 11
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 12
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 13
(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 14
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-bromobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 15
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 16
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 17
(R) -N- (1- (4,5-bis (2- (1H-indol-3-yl) ethyl) -4H-1,2,4-triazol-3-yl) -2- (1H- indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 18
(S) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 19
(R) -N- (1- (4- (3-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 20
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 21
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3,5-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 22
(R) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-2-methylpropanamide,
Compound 23
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 24
(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5- (3- (1H-indol-3-yl) propyl) -4H-1,2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 25
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2-methoxy) benzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 26
(R) -N- (1- (4- (2-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 27
(R) -N- (2- (1H-indol-3-yl) -1- (4- (naphthalen-1-ylmethyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 28
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3,4-dichlorobenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 29
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-fluorobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 30
(R) -N- (1- (4- (4-fluorobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 31
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) piperidin-4-carboxamide,
Compound 32
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) piperidin-3-carboxamide,
Compound 33
(R) -N- (1- (4- (4-methylbenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-amino-2-methylpropanamide,
Compound 34
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methylbenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 36
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) piperidin-2-carboxamide,
Compound 37
(R) -N- (1- (4- (4-methylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 38
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide,
Compound 39
(R) -N- (1- (5-benzyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 40
(2S, 4R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole- 3-yl) ethyl) -4-hydroxypyrrolidin-2-carboxamide,
Compound 41
(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-3-carboxamide,
Compound 42
(R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-3-carboxamide,
Compound 43
(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 44
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 45
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) piperidin-4-carboxamide,
Compound 46
(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) pyrrolidin-2-carboxamide,
Compound 47
(R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) pyrrolidin-2-carboxamide,
Compound 48
(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-2-carboxamide,
Compound 49
(R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-2-carboxamide,
Compound 50
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 51
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 52
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-4-yl) acetamide,
Compound 53
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) cyclohexanecarboxamide,
Compound 54
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) piperidin-4-carboxamide,
Compound 55
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) piperidin-3-carboxamide,
Compound 56
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3-aminopropanamide,
Compound 57
(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-aminopropanamide,
Compound 58
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide,
Compound 59
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3- (pyridin-3-yl) propanamide,
Compound 60
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 61
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 62
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 63
(R) -N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole- 3-yl) ethyl) piperidin-2-carboxamide,
Compound 64
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,
Compound 65
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,
Compound 66
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,
Compound 67
(R) -N- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine -2-carboxamide,
Compound 68
(S) -N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole- 3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 69
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 70
(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazole -3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 71
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) pyrazin-2-carboxamide,
Compound 72
(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide,
Compound 73
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) picolinamide,
Compound 74
(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) ethanamine,
Compound 75
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 76
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,
Compound 77
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,
Compound 78
(R) -N-1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine -2-carboxamide,
Compound 79
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
Compound 80
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) picolinamide,
Compound 81
(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) ethyl) piperazin-2-carboxamide,
Compound 82
(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 83
(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 84
(R) -N-1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine -2-carboxamide,
Compound 85
(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,
Compound 86
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-cis-aminocyclohexanecarboxamide,
Compound 87
(R) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) piperidin-3-carboxamide,
Compound 88
(R) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide,
Compound 89
(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 90
(R) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 91
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 92
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-bromobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 93
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2-phenylethyl) -2-amino-2-methylpropanamide,
Compound 94
(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (thiophen-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 95
(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,
Compound 96
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4-methyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole -3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 97
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-methyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 98
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl ) ethyl) -2-amino-2-methylpropanamide,
Compound 99
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 100
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-methyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 101
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 102
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 103
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 104
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole -3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 105
(R) -N- (1- (5-benzyl-4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide,
Compound 106
(R) -N- (1- (5-benzyl-4- (2,2-diphenylethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 107
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,2-diphenylethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 108
(R) -N- (1- (4- (3,5-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 109
(R) -N- (1- (4,5-dibenzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2 methylpropanamide
Compound 110
(R) -N- (1- (5-benzyl-4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide,
Compound 111
(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 112
(S) -N- (1- (4- (2,4-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 113
(R) -N- (1- (4- (3,5-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 114
(R) -N- (1- (4- (4-bromobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 115
(R) -N- (1- (4- (2-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 116
(S) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 117
(R) -N- (1- (4,5-diphenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2 methylpropanamide
Compound 118
(R) -N - [- (1- (4- (3,4-dichlorobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-amino-2-methylpropanamide,
Compound 119
(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) ethanamine,
Compound 120
(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide,
Compound 121
(R) -N- (1- (4- (4-fluorobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 122
(R) -N- (1- (4- (3,4-dichlorobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 124
(R) -N- (1- (4- (4-methylbenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 125
(S) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-2-methylpropanamide,
Compound 126
(S) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 128
N - ((R) -1- (4- (4-nitrobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 129
(S) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 130
(R) -N- (1- (4- (4-methoxyphenethyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 131
(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (thiophen-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 132
(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 133
(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) piperidine-3-carboxamide,
Compound 134
(S) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) pyrrolidin-2-carboxamide,
Compound 135
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 136
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2- (pyridn-4-yl) acetamide,
Compound 137
(2R) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-2-carboxamide,
Compound 138
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
Compound 139
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminopyridine-3-carboxamide,
Compound 140
(2S) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-aminopropanamide,
Compound 141
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,
Compound 142
N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) piperidin-4- carboxamide
Compound 143
(2S) -N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) pyrrolidine-2-carboxamide,
Compound 144
N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) -2-aminoacetamide ,
Compound 145
N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) -2- ( pyridin-2-yl) acetamide,
Compound 146
N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) picolinamide,
Compound 147
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) picolinamide,
Compound 148
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 149
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 150
(2S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 152
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 153
N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-trans-aminocyclohexanecarboxamide,
Compound 154
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide,
Compound 155
(3S) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-3-carboxamide,
Compound 156
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide,
Compound 157
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) picolinamide,
Compound 158
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) piperidin-4-carboxamide,
Compound 159
N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) picolinamide,
Compound 160
N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 161
N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) pyrazine-2-carboxamide,
Compound 162
N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) -2-aminoacetamide,
Compound 163
N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 164
N - ((R) -1- (5-benzyl-4 - ((pyridin-2-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) picolinamide,
Compound 165
N - ((R) -1- (5-benzyl-4 - ((pyridin-2-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-acetamide,
Compound 166
N - ((R) -1- (5-benzyl-4 - ((pyridin-2-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) piperidine-4-carboxamide,
Compound 167
N - ((R) -1- (5-benzyl-4 - ((pyridin-4-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,
Compound 168
N - ((R) -1- (5- (4-methoxybenzyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 169
N - ((R) -1- (5-benzyl-4 - ((pyridin-4-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) picolinamide,
Compound 170
N - ((R) -1- (5-benzyl-4 - ((pyridin-4-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) 2-amino-acetamide,
Compound 171
(R) -benzyl-3- (2-aminoisobutyramido) -3- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4- triazol-3-yl) propanoate,
Compound 172
N - ((R) -1- (5-benzyl-4 - ((pyridin-3-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,
Compound 173
N - ((R) -1- (4-benzyl-5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide,
Compound 174
N - ((R) -2- (1H-indol-3-yl) -1- (4-methyl-5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) picolinamide,
Compound 175
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 176
N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) benzamide,
Compound 177
(R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) -N- phenylmethanesulfonylamine,
Compound 178
(R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) -N- tosilethanamine,
Compound 179
N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 180
N-1 - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) ethane-1,2-diamine,
Compound 181
N - ((R) -1- (4 - ((furan-2-yl) methyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,
Compound 182
N - ((R) -1- (4 - ((furan-2-yl) methyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) picolinamide,
Compound 183
N - ((R) -1- (4 - ((furan-2-yl) methyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) piperidine-4-carboxamide,
Compound 184
N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) tetrahydro-2H-pyran-4-carboxamide,
Compound 185
N - ((R) -1- (5 - ((1H-indol-3-yl) methyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 186
(2S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-3-phenylpropanamide,
Compound 187
(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) -N-tosilethanamine,
Compound 188
N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -4-azidobenzamide,
Compound 189
N-benzyl- (R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl ) ethanamine,
Compound 190
(2S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) -2,5-dihydro-1H-pyrrole-2-carboxamide. 10. The method according to claim 1, in which the antagonist of SSHR receptors is selected from the group of compounds comprising compound 1,3, 12, 13, 14, 18, 20, 22, 23, 33, 36, 37, 38, 41, 46 , 47, 48, 49, 50, 51, 52, 53, 57, 58, 59, 60, 61, 63, 64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 76 , 77, 79, 80, 82, 85, 86, 87, 88, 89, 90, 91, 93, 101, 102, 109, 114, 116, 119, 134, 135, 136, 137, 138, 139, 140 , 145, 146, 147, 148, 150, 152, 153, 154, 156, 157, 159, 160, 161, 164, 171, 174, 176, 178, 179, 182, 184, 186, 188 and / or the compound 190. 11. The method according to claim 5, in which the agonist of SSHR receptors is selected from the group comprising compound 2, 4, 5, 6, 7, 8, 9, 10, 11, 15, 16, 17, 19, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 39, 40, 42, 43, 44, 45, 54, 55, 56, 62, 67, 78, 81, 83, 84, 87, 92, 94, 99, 103, 104, 105, 106, 107, 108, 110, 111, 115, 117, 118, 121, 122, 124, 130, 131, 142, 155, 158, 163, 173, 175, 180, 181, 183, 185 and / or compound 187. 12. The method according to claim 1, in which the SSHR receptors are selected from the group comprising GHS receptors type 1, GHS-R1a, GHS-R1b, motilin receptor, motilin receptor 1a, neurotensin receptor, TRH receptor, GPR38 (FM1) , GPR39 (FM2), FM3, subtype GHS-R, SSHR-binding site, heart muscle GHS-R, breast GHS-R, preferably selected from the group including type 1 GHS receptors, GHS-R1a, GHS-R1b, and most preferably GHS-R1a. 13. The method according to claim 1, in which the drug contains at least one additional pharmacologically active substance compatible with the compound specified in paragraph 1 of the formula, by its effect on the body in the composition of the drug. 14. The method according to item 13, in which the additional pharmacologically active substance is a CCG receptor antagonist and an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant [1H-pyrazole-3-carboxamide, 5- (4- chlorophenyl) -1- (2,4-dichlorophenyl) -4-methyl-N-1-piperidinyl-, monohydrochloride]. 15. The method according to claim 1, in which the drug is used before, during and / or after treatment with at least one additional pharmacologically active substance compatible with the compound specified in claim 1 of the formula, according to its effect on the body. 16. The method according to clause 15, in which the drug contains a CCGR receptor antagonist, and the additional pharmacologically active substance is an endocannabinoid receptor antagonist, preferably a CB 1 receptor antagonist, most preferably rimonabant [1H-pyrazole-3-carboxamide, 5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methyl-N-1-piperidinyl-, monohydrochloride]. 17. Triazoles selected from the group including
Compound 1
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 2
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 3
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 4
(R) -N- (1- (5-benzyl-4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 5
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 6
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 7
(R) -N- (1- (4- (3-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 8
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 9
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 10
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 11
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (naphthalen-1-ylmethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 12
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 13
(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 14
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-bromobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 15
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 16
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 17
(R) -N- (1- (4,5-bis (2- (1H-indol-3-yl) ethyl) -4H-1,2,4-triazol-3-yl) -2- (1H- indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 18
(S) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 19
(R) -N- (1- (4- (3-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 20
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 21
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3,5-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 22
(R) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-2-methylpropanamide,
Compound 23
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 24
(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5- (3- (1H-indol-3-yl) propyl) -4H-1,2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 25
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2-methoxy) benzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 26
(R) -N- (1- (4- (2-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 27
(R) -N- (2- (1H-indol-3-yl) -1- (4- (naphthalen-1-ylmethyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 28
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3,4-dichlorobenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 29
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-fluorobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 30
(R) -N- (1- (4- (4-fluorobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 31
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) piperidin-4-carboxamide,
Compound 32
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) piperidin-3-carboxamide,
Compound 33
(R) -N- (1- (4- (4-methylbenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-amino-2-methylpropanamide,
Compound 34
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methylbenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 36
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) piperidin-2-carboxamide,
Compound 37
(R) -N- (1- (4- (4-methylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 38
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide,
Compound 39
(R) -N- (1- (5-benzyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 40
(2S, 4R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole- 3-yl) ethyl) -4-hydroxypyrrolidin-2-carboxamide,
Compound 41
(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-3-carboxamide,
Compound 42
(R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-3-carboxamide,
Compound 43
(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 44
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 45
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) piperidin-4-carboxamide,
Compound 46
(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) pyrrolidin-2-carboxamide,
Compound 47
(R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) pyrrolidin-2-carboxamide,
Compound 48
(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-2-carboxamide,
Compound 49
(R) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-2-carboxamide,
Compound 50
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 51
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 52
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-4-yl) acetamide,
Compound 53
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) cyclohexanecarboxamide,
Compound 54
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) piperidin-4-carboxamide,
Compound 55
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) piperidin-3-carboxamide,
Compound 56
(R) -N - [- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3-aminopropanamide,
Compound 57
(S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-aminopropanamide,
Compound 58
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide,
Compound 59
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3- (pyridin-3-yl) propanamide,
Compound 60
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 61
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 62
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 63
(R) -N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole- 3-yl) ethyl) piperidin-2-carboxamide,
Compound 64
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,
Compound 65
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,
Compound 66
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,
Compound 67
(R) -N-1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl ) piperazine-2-carboxamide,
Compound 68
(S) -N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole- 3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 69
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 70
(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazole -3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 71
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) pyrazin-2-carboxamide,
Compound 72
(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide,
Compound 73
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) picolinamide,
Compound 74
(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) ethanamine,
Compound 75
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 76
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,
Compound 77
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,
Compound 78
(R) -N-1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine -2-carboxamide,
Compound 79
(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
Compound 80
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) picolinamide,
Compound 81
(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H indol-3-yl) ethyl) piperazin-2-carboxamide,
Compound 82
(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 83
(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 84
(R) -N-1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine -2-carboxamide,
Compound 85
(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,
Compound 86
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-cis-aminocyclohexanecarboxamide,
Compound 87
(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) piperidin-3-carboxamide,
Compound 88
(R) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide,
Compound 89
(S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 90
(R) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 91
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 92
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-bromobenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 93
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2-phenylethyl) -2-amino-2-methylpropanamide,
Compound 94
(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (thiophen-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 95
(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,
Compound 96
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4-methyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole -3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 97
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-methyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 98
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl ) ethyl) -2-amino-2-methylpropanamide,
Compound 99
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 100
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-methyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 101
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 102
(R) -N- (1- (4- (2,4-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 103
(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 104
(R) -N- (1- (5 - ((1H-indol-3-yl) methyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole -3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 105
(R) -N- (1- (5-benzyl-4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide,
Compound 106
(R) -N- (1- (5-benzyl-4- (2,2-diphenylethyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 107
(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,2-diphenylethyl) -4H-1,2,4-triazol-3-yl ) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 108
(R) -N- (1- (4- (3,5-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 109
- (R) -N- (1- (4,5-dibenzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino 2-methylpropanamide,
Compound 110
(R) -N- (1- (5-benzyl-4-hexyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide,
Compound 111
(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 112
(S) -N- (1- (4- (2,4-dimethoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 113
(R) -N- (1- (4- (3,5-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 114
(R) -N- (1- (4- (4-bromobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 115
(R) -N- (1- (4- (2-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 116
(S) -N- (1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 117
(R) -N- (1- (4,5-diphenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2 methylpropanamide
Compound 118
(R) -N- (1- (4- (3,4-dichlorobenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 119
(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) ethanamine,
Compound 120
(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide,
Compound 121
(R) -N- (1- (4- (4-fluorobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 122
(R) -N- (1- (4- (3,4-dichlorobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 124
(R) -N- (1- (4- (4-methylbenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 125
(S) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-2-methylpropanamide,
Compound 126
(S) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 128
N - ((R) -1- (4- (4-nitrobenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 129
(S) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 130
(R) -N- (1- (4- (4-methoxyphenethyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 131
(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (thiophen-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 132
(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 133
(R) -N- (2- (lH-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1,2,4-triazol-3-yl) ethyl) piperidine-3-carboxamide,
Compound 134
(S) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) pyrrolidin-2-carboxamide,
Compound 135
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 136
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2- (pyridin-4-yl) acetamide,
Compound 137
(2R) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-2-carboxamide,
Compound 138
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
Compound 139
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminopyridine-3-carboxamide,
Compound 140
(2S) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) -2-aminopropanamide,
Compound 141
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,
Compound 142
N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) piperidin-4- carboxamide
Compound 143
(2S) -N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) pyrrolidine-2-carboxamide,
Compound 144
N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) -2-aminoacetamide ,
Compound 145
N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) -2- ( pyridin-2-yl) acetamide,
Compound 146
N - ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1,2,4-triazol-3-yl) ethyl) picolinamide,
Compound 147
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) picolinamide,
Compound 148
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 149
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 150
(2S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) pyrrolidin-2-carboxamide,
Compound 152
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3-yl) - 2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,
Compound 153
N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-trans-aminocyclohexanecarboxamide,
Compound 154
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide,
Compound 155
(3S) -N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3- il) ethyl) piperidine-3-carboxamide,
Compound 156
N - ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide,
Compound 157
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) picolinamide,
Compound 158
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) piperidin-4-carboxamide,
Compound 159
N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) picolinamide,
Compound 160
N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,
Compound 161
N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) pyrazine-2-carboxamide,
Compound 162
-N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl ) ethyl) -2-aminoacetamide,
Compound 163
N - ((R) -2- (1H-indol-3-yl) -1- (4- (2,4-dimethoxyphenyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) piperidine-4-carboxamide,
Compound 164
N - ((R) -1- (5-benzyl-4 - ((pyridin-2-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) picolinamide,
Compound 165
N - ((R) -1- (5-benzyl-4 - ((pyridin-2-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-acetamide,
Compound 166
N - ((R) -1- (5-benzyl-4 - ((pyridin-2-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) piperidine-4-carboxamide,
Compound 167
N - ((R) -1- (5-benzyl-4 - ((pyridin-4-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,
Compound 168
N - ((R) -1- (5- (4-methoxybenzyl) -4-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 169
N - ((R) -1- (5-benzyl-4 - ((pyridin-4-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) picolinamide,
Compound 170
N - ((R) -1- (5-benzyl-4 - ((pyridin-4-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-acetamide,
Compound 171
(R) -benzyl-3- (2-aminoisobutyramido) -3- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4- triazol-3-yl) propanoate,
Compound 172
N - ((R) -1- (5-benzyl-4 - ((pyridin-3-yl) methyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,
Compound 173
N - ((R) -1- (4-benzyl-5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino -2-methylpropanamide,
Compound 174
N - ((R) -2- (1H-indol-3-yl) -1- (4-methyl-5-phenethyl-4H-1,2,4-triazol-3-yl) ethyl) picolinamide,
Compound 175
N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1,2,4-triazol-3-yl) -2- (1H -indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 176
N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) benzamide,
Compound 177
(R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) -11- phenylmethanesulfonylamine,
Compound 178
(R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) -N- tosilethanamine,
Compound 179
N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 180
N-1 - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) ethane-1,2-diamine,
Compound 181
N - ((R) -1- (4 - ((furan-2-yl) methyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) -2-amino-2-methylpropanamide,
Compound 182
N - ((R) -1- (4 - ((furan-2-yl) methyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) picolinamide,
Compound 183
N - ((R) -1- (4 - ((furan-2-yl) methyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3 -yl) ethyl) piperidine-4-carboxamide,
Compound 184
N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) tetrahydro-2H-pyran-4-carboxamide,
Compound 185
N - ((R) -1- (5 - ((1H-indol-3-yl) methyl) -4- (3-methoxybenzyl) -4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,
Compound 186
(2S) -N - ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indole-3- il) ethyl) -2-amino-3-phenylpropanamide,
Compound 187
(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2,4-dimethoxybenzyl) -4H-1,2,4-triazol-3-yl) -2 - (1H-indol-3-yl) -N-tosilethanamine,
Compound 188
N - ((R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -4-azidobenzamide,
Compound 189
N-benzyl- (R) -1- (4- (2,4-dimethoxybenzyl) -5-phenethyl-4H-1,2,4-triazol-3-yl) -2- (1H-indol-3-yl ) ethanamine,
Compound 190
(2S) -N - ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1,2,4-triazol-3 -yl) -2- (1H-indol-3-yl) ethyl) -2,5-dihydro-1H-pyrrole-2-carboxamide. 18. A pharmaceutical composition for treating or preventing physiological and / or pathophysiological conditions mediated by growth hormone secretion receptors (SSHR receptors) and selected from the group including growth retardation, cachexia, short-term, medium-term and / or long-term regulation of energy balance; short-term, medium-term and / or long-term regulation (stimulation and / or inhibition) of food intake; adipogenesis, obesity and / or obesity; an increase and / or decrease in body weight in mammals, characterized in that it contains at least one compound according to claim 17 in a pharmacologically effective amount. 19. The pharmaceutical composition according to p. 18, characterized in that the active ingredient is present in a single dose, comprising from 0.001 to 100 mg per kg of body weight of the patient. 20. The pharmaceutical composition according to p. 18, characterized in that it further comprises at least one pharmaceutically acceptable carrier and / or excipient. 21. The pharmaceutical composition according to claim 18, characterized in that it contains at least one additional pharmacologically active substance compatible with the compound indicated in claim 19 in its effect on the body in the composition of the drug. 22. The pharmaceutical composition according to item 21, wherein the additional pharmacologically active substance is an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant [1H-pyrazole-3-carboxamide, 5- (4-chlorophenyl) -1- (2,4-dichlorophenyl) -4-methyl-N-1-piperidinyl-, monohydrochloride].

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