3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to a compound of Formula

,

where Y represents a group of formula -(CR9R10)-; X is selected from the group, consisting of -C(=O)-, -OC(=O)-, -NHC(=O)-, -(CR11R12)- and -S(-O)2-; Z represents a group of formula -(CR13R14)q-; R1 is selected from the group, consisting of C1-C12alkyl, optionally substituted with one substituent, selected from naphthyl, indole and biphenyl; C2-C12alkenyl, substituted with a substituent, selected from thienyl, naphthyl and phenyl, with the said phenyl being optionally substituted with 1-2 substituents; selected from halogen, trifluoroalkyl, C1-C6alkyl, methoxy and hydroxy; C3-C6cycloalkyl; C6-C10aryl, optionally substituted with 1-2 substituents, selected from halogen, phenyl, amino, phenoxy, C1-C6alkyl, methoxy, hydroxyl and carboxy; and C4-C9heteroaryl, selected from indole, quinoline, quinoxaline, benzofuranyl, benzothiophene, benzimidazole, benzotriazole, benzodioxin, benzothiasole, pyrazole, furyl and isoxazole, optionally substituted with a substituent, selected from C1-C6alkyl and phenyl; R2 and R3 each is independently selected from the group, consisting of H and C1-C12alkyl; R4a is selected from the group, consisting of H, C1-C12alkyl, optionally substituted with phenyl; C2-C12alkenyl, C3-C6cycloalkyl, C6aryl, C(=O)R15, C(=O)NR15R16, C(=O)OR15, SO2R15 and -C(=NR15)-NR16R17; R4d represents hydrogen or R4a and R4b, taken together with a nitrogen atom, which they are bound to, form an optionally substituted heterocyclic fragment, selected from piperidine, morpholine, pyrrolidine and azetidine, where the substituent is selected from C1-C12alkyl, hydroxy, halogen, carboxy and oxo; each R5a and R5b represents H, or R6, R7 and R8 each is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6-C10aryl, optionally substituted with halogen, or taken together with a carbon atom, which they are bound to, two or more of R6, R7 and R8 form a fragment, selected from the group, consisting of C2-C12alkenyl; C3-C6cycloalkyl, optionally substituted with C1-C6alkyl; C6aryl, optionally substituted with 2 substituents, selected from halogen; each R9 and R10 represents H or C1-C12alkyl, substituted with naphthyl; each R11 and R12 represents H; R13 and R14 represent H, or each R15, R16 and R17 is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6aryl, substituted with one substituent, selected from C1-C6alkyl; and C5-heteroaryl, additionally containing one nitrogen atom, with the said heteroaryl representing pyridyl; q represents an integer number, selected from the group, consisting of 2, 3 and 4; r represents 1; or its pharmaceutically acceptable salt. The invention also relates to particular compounds of 1,4-diazepan-2-one derivatives.

EFFECT: obtaining 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists.

21 cl, 7 tbl, 110 ex

 

The SCOPE of the INVENTION

This invention relates to antagonists of melanocortin-5 receptor. In particular this invention relates to the family of 1,4-diazepan-2-ones and derivatives thereof, which are antagonists of the melanocortin-5 receptor. This invention also relates to pharmaceutical compositions containing these compounds.

BACKGROUND of the INVENTION

Melanocortin-5 receptor (MC5R) is coupled with G-protein receptor (GPCR), belonging to the family of melanocortin receptors. There are five melanocortin receptors have been identified and cloned to date: MC1R, MC2R, MC3R, MC4R and MC5R. Melanocortin receptors are involved in various physiological functions, providing a number of opportunities for therapeutic intervention in physiological processes by changing (i.e. statistically significant increase or decrease) or modulation (e.g., increasing regulation or downward regulation) signal activity melanocortin receptor.

Published reviews of melanocortin receptors and their potential as targets for therapy (Wikberg 2001; Bohm 2006). The members of the family of melanocortin receptors are regulated peptide agonists such as ACTH (adrenocorticotropic hormone), and melanocyte-stimulating gormo the AMI (α, β-, γ-MSH)derived from proopiomelanocortin (O.G. ROMs), and peptide antagonists, such as Agouti-signaling protein (ASP) and Agouti-related protein (AGRP). MC1R is widely expressed and is associated with pigmentation in melanocytes and inflammatory responses in many cells involved in the immune system. MC2R is different from other melanocortin receptors because it connects only asthma, but not MSH ligands. He is highly expressed in the adrenal gland and regulates the synthesis of corticosteroids. MC3R is found in the brain but also in other places in the body and, as it turns out, plays a role in the regulation of energy homeostasis and possible sexual dysfunction. MC4R actually occurs only in the brain, according to some data there and in other places. It is closely related to power control, and is also associated with sexual desire. MC5R is widely expressed in peripheral tissues, especially in the exocrine glands, with a number of receptor is also expressed in the brain. Taking into account the coverage of the activity associated with melanocortin receptors, is necessary when aiming at the target of one of these receptors do it selectively avoid the side effects associated with antagonism or agonism other receptors in this family.

MC5R has cloned and expressed from a variety of species, including people who in 1993 (although called MC2 in this document) (Chhajlani 1993), rat in 1994 (Griffon 1994), mice in 1994 (Gantz 1994; Labbé 1994) and in 1995 (Fathi 1995), representative of the family dog (Houseknecht 2003), rhesus (Huang 2000), sheep (Barrett 1994), striped pertino (Ringholm 2002), silver carp (Cerdá-Reverter 2003), prickly shark (Klovins 2004), rainbow trout (Haitina 2004) and chicken (Ling 2004), using the MC5R gene, also identified in pigs (Kim 2000). Published patents covering MC5R sequence in humans (Wikberg 2002), mice (Yamada 1997), rhesus (Fong 2003) and dogs (Houseknecht 2003).

A number of studies link MC5R regulating oil secretions, as summarised in 2006 (Zhang 2006). Mice that lack MC5R, have a reduced sebum production, as evidenced by a marked inability to discharge the water from their fur and reduced the amount of sebum extracted from their wool. Largely these mice the rest were generally healthy, with no visible abnormalities (appearance, behavior, growth, muscle mass, fat mass, reproduction, levels of basal and stress-induced corticosterone, glucose and insulin) (Chen 1997). Further research has identified the reduction of pheromones, causing changes in aggressive behavior between mice (Caldwell 2002; Morgan, 2004; Morgan 2004b; Morgan 2006). A mouse whose O.G. ROMs-derived peptide of the native ligands MC5R "knocked out", show a similar phenotype (Yaswen 1999). Rats injected is-MSH, had increased by 30-37% of normal sebum production, while removing the intermediate lobe of the hypophysis (source MSH) caused a reduction in oil secretion by 35%, which was restored after administration of α-MSH (Thody 1973). A synergistic effect between α-MSH and testosterone was observed in rats, while testosterone increases sebaceous gland and cell volumes (probably through increased proliferation), α-MSH increases groovetune skin, and the combination increases the excretion of fat (Thody 1975a; Thody 1975 b).

By detecting MC5R transcripts in microarcsecond sebaceous glands (Thiboutot 2000), detection of MC5R in human facial sebaceous glands staining using immune labels (Hatta 2001), detection MC5R mRNA and MC5R in human sebaceous glands, cultured human sebocyti and rat prepucialna cells (Thiboutot 2000) and detection of MC5R in the form punctate particles in the sebaceous glands staining of polyclonal antibodies, it was shown that at the cellular level of the human sebocyti Express MC5R, which can be seen in differentiated, but not undifferentiated sebocyti (Zhang 2006). MC5R mRNA is also found in the sebaceous glands of the skin of wild-type mice, but not in the skin section "MC5R-knocked out mice (Chen 1997). Treatment of human sebocyti by cholera toxin (ChT), an extract of the pituitary bull is (TIME), α-MSH or NDP-MSH increases the formation of lipid droplets, the synthesis of squalene and the expression of MC5R (Zhang 2003; Zhang 2006). While and MC1R and MC5R found in fat cells, the processing of the primary sebocyte cell culture human NDP-MSH or TIME aroused considerable increase in expression of MC5R compared to serum-free conditions, correlating with the differentiation of sebocyti. An immortalized line of fat cells (SZ-95, TSS-1 and SEB-1) also demonstrate the expression of MC5R (Jeong 2007; Smith 2007a; Phan 2007). These studies suggest that MC5R antagonists can be used to reduce the oil secretion in mammals and, therefore, in the treatment of conditions associated with excessive excretion of fat.

It was found that the family 1,2,4-thiadiazoline derivatives with antagonistic activity of MC5R (138-320 nm) reduces saloobrazovanie as in cultures of human cells sebocyti, and when applied topically to human skin transplanted onto immunodeficient mice (Eisinger 2003a-d; 2006a, b).

Excessive excretion of fat, or seborrhea, is a common ailment. Sebaceous glands are found in most parts of the body with dense concentrations of large glands on the face, scalp scalp and upper body (Simpson and Cunliffe p43.1). Excretion of fat depends in part on androgenic hormones, possibly partially mediates the I 5α-reductase, which converts testosterone to 5α-DHT (dihydrotestosterone). Sebum consists of species-specific mixtures of lipids. In humans it consists of approximately 58% of glycerides, 26% of complex wax esters, 12% squalene and 4% cholesterol/esters of cholesterol (Simpson and Cunliffe p43.5). The presence of squalene is almost exclusive feature of human sebum. The function of sebum is not clearly defined, but it is believed that it has fungistatic properties and plays a role in the loss of moisture from the epidermis and its waterproof abilities (Simpson and Cunliffe p43.6; Danby 2005; Porter 2001; Shuster 1976; Kligman 1963).

Excessive excretion of fat associated with the development of common acne. Common acne are a common disease, affecting approximately 80% of the world population at some stage of life. A person more likely to develop acne than any other disease, although the severity varies considerably (Simpson and Cunliffe p43.16). Acne peaks in prevalence and severity in adolescents aged 14-19 years, with approximately 35-40% of the affected, but a significant number of patients (7-24%) it manifests itself after the age of 25 (Simpson and Cunliffe p43.15). Patients suffering from acne, one study found that 80% still had symptoms at 30-40 years of age (Simpson and Cunliffe p43.16). Despite the fact that acne is not dangerous for the LM is no disease, it can greatly affect the quality of life of patients (Follador 2006), while one study of patients with severe acne demonstrates the effect similar to more serious chronic medical conditions such as asthma, epilepsy, diabetes, back pain or arthritis (Mallon 1999).

It is believed that four main factors cause the pathogenesis of acne: (i) increased production of sebum (seborrhea), (ii) hyperuricaemia/blockage of the duct that are related to hair and sebaceous glands (acne), (iii) infection of a duct of P. acnes, and (iv) the duct inflammation related to hair and sebaceous gland (Simpson and Cunliffe p43.15; Williams 2006). A number of studies have shown a clear link between increased production of sebum and the presence and severity of acne (Simpson and Cunliffe p43.17; Youn 2005; Pierard 1987; Harris 1983; Cotterill 1981; Thody 1975; Pochi 1964). A study in 2007 he established the relationship between sebum excretion and the development of acne in children in prepod sprout age (Mourelatos 2007). Sebum is the main nutrient P. acnes, thus reducing sebum will reduce subsequent bacterial infection and inflammatory response.

Androgenic sex hormones, seems to play a role in the development of acne, with a strong correlation with the production of sebum (Makrantonaki 2007). Pills two oral contraceptives approved by the FDA (Commission on the counter is Liu for drugs and nutrients) for the treatment of common acne (Harper 2005), and these compounds apparently act by reducing the androgen-mediated saloobrazovanie. Diet (Cordain 2005; Smith 2007b), stress (Zouboulis, 2004) and genetic factors (Goulden 1999; Bataille 2006) also may play a role in the appearance of acne, again potentially through increased production of sebum.

Current methods of treatment of common acne primarily focused on the treatment of infections and inflammatory stages of the disease with the help of a large number of different compositions methodistic antibiotics (for example, benzoyl peroxide, tetracycline, erythromycin, clindamycin) and retinoids (e.g., retinoic acid, isotretinoin, adapalene, tazarotene)used single or in combination; some also have anti-inflammatory action (Simpson and Cunliffe p43.36-43.38). Many of these treatments have limited effectiveness, especially in severe cases of acne. A growing problem is the development of antibiotic-resistant strains of P. acnes (Simpson and Cunliffe p43.37, 43.46; Williams 2006). As Metodista retinoids and benzoyl peroxide cause skin irritation, and retinoids can cause photosensitivity (Williams 2006). Oral treatments include isotretinoin, antibiotics, hormones and steroids. It has been shown that the females antiandrogens reduce sebum sa is a (approximately 40-80%, although no placebo control group) and reduce acne (Simpson and Cunliffe p43.44; Burke 1984; Goodfellow 1984). Laser and based on UV therapy are common, and are expected to act by heating of sebaceous glands with subsequent reduction saloobrazovanie; with reduction as saloobrazovanie and measured acne lesions (Jih 2006; Bhardwaj 2005). Of the many therapies that are suitable for acne, only oral isotretinoin and hormonal therapy act by regulating the sebaceous glands to reduce oil secretions (Clarke 2007).

The most effective treatment of acne, oral isotretinoin (13-CIS-retinoic acid, Roaccutane, Accutane, was introduced in 1983 and still remains the most clinically effective treatment against acne. This is the only known treatment with strong suppressive activity on the production of fat, reduce sebum excretion up to 90% after 8-12 weeks of therapy (60-70% after 2 weeks) (Simpson and Cunliffe p43.47; Jones 1983; Goldstein 1982; King 1982). Metodista retinoids, in contrast, no effect on sebum production. Oral isotretinoin is also anti-inflammatory, reduces the appearance of acne and reduces infection of P. acnes. The mechanism of action is still unclear, and, apparently, an important role is played by the metabolites of isotretinoin. Isotretinoin induces apoptosis and termination CL is the exact cycle in human immortalizing SEB-1 sebocytes cell culture (Nelson 2006). Unfortunately, oral isotretinoin has serious side effects; largely it is teratogens and it needs a registration program for use in the United States. The FDA has issued a warning against online purchase of isotretinoin. During treatment also recommend blood testing for lipids, hold on an empty stomach, and the liver (Williams 2006). Isotretinoin was associated (though not significantly) with adverse psychological effects, including suicide and depression (Marqueling 2005).

Other forms of acne, such as nodular acne or fulminant acne, may also be reacting to a substance that reduces the secretion of sebum. Seborrhea, or excessive production of sebum is often associated with severe acne condition. Seborrheic dermatitis (SD) is a skin disease associated with rich skin fat areas of the scalp, face and trunk, scaly, flaky, itchy redness of the skin, affecting 3-5% of the population; dandruff is a mild form of dermatitis that affects 15-20% of the population. Seborrhea and diabetes occur more frequently in patients with Parkinson's disease or affective disorders (paralysis of the facial nerve, supraorbital damage, polio, syringomyelia, quadriplegia, unilateral damage in Gusarova ganglia and those with HIV/AIDS) (Plewig 1999). the surveys showed that seborrheic dermatitis is also associated with chronic alcoholic pancreatitis, hepatitis C virus, and various cancers. It also commonly occurs in patients with genetic disorders such as down syndrome, a disease Hailey-Hailey and cardio-Faccio-cutaneous syndrome (Gupta 2004). To treat these symptoms MC5R antagonists can be used.

Although few in number, but described in different tumors affecting the sebaceous glands or fat cells (for example, Ide, 1999; Mariappan 2004; Kruse 2003). Syndrome Muir-Torre includes adenoma sebaceous glands associated with the internal adenocarcinoma (usually the colon, breast, ovarian or prostate). Preventing the differentiation of fat cells can provide an effective treatment for relief of tumor growth. With this purpose used oral isotretinoin (Graefe 2000). The sebaceous gland hyperplasia is a benign hyperplasia of the sebaceous glands, forming a small yellowish papules on the surface of the skin, usually the face. The disease is associated with excessive proliferation of undifferentiated sebocyti, but not with excessive samoobrazovaniem. Ectopic sebaceous glands (granules, Fordyce) are similar to yellow papules detected in the mouth or on the body of the penis. And those, and others respond to oral isotretinoin. Effective treatment of magleby be a connection, which reduces the proliferation of sebocyti.

α-MSH demonstrates immunosuppressive effect by inhibiting the number of inflammatory responses, and MC5R are involved in these immunomodulatory activity. It was found that MC5R mRNA is expressed at high levels in human CD4+ T-helper (Th) cells and at moderate levels in other human peripheral blood leukocytes (Andersen 2005). In mice MC5R found in lymphoid organs (Labbé, 1994), and MC5R found on the surface of murine Pro-B-limfozitah cells, where he, as it turned out, mediates α-MSH activation of JAK2 signaling pathway, enhancing cell proliferation (Buggy 1998). The induction of CD25+ CD4+ regulatory T cells with α-MSH also, as it turned out, through MC5R (Taylor 2001).

Due to the above reasons it would be desirable to provide MC5R antagonists that could be applied in a number of therapeutic areas. Therapeutic regulation of biological signal transduction comprises modulation MSR-mediated cellular events, including, inter alia, inhibition or potentiation of the interaction among MSR-binding and activating or deactivating molecules or other substances that regulate the activity of MC5R. Increased capacity for such regulation MC5R can contribute to the development way is to modulate the sebaceous excretions or other biological processes and treating conditions associated with such paths, such as acne, as described above.

Applicants have identified a family of 1,4-diazepan-2-ones, which show the activity of MC5R antagonist, which will be useful in the treatment of conditions associated with MC5R.

BRIEF description of the INVENTION

This invention provides compounds of formula (I):

,

where:

Y represents a group of formula -(CR9R10)n-;

X is selected from the group comprising-C(=O)-, -OC(=O)-, -NHC(=O)-, -(CR11R12)sand-S(=O)2-;

Z represents a group of formula -(CR13R14)q-;

R1selected from the group comprising H, optionally substituted C1-C12alkyl, optionally substituted C2-C12alkenyl, optionally substituted C2-C12quinil, optionally substituted C1-C12heteroalkyl, optionally substituted C3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl;

R2and R3each independently selected from the group comprising H, optionally substituted C1-C12alkyl, optionally substituted C2-C12alkenyl, optionally substituted C -C12quinil, optionally substituted C1-C12heteroalkyl, optionally substituted C3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl;

R4aselected from the group comprising H, optionally substituted C1-C12alkyl, optionally substituted C2-C12alkenyl, optionally substituted C2-C12quinil, optionally substituted C1-C12heteroalkyl, optionally substituted C3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optionally substituted C6-C18aryl, optionally substituted C1-C18heteroaryl, C(=O)R15With(=O)NR15R16C(=O)OR15, SO2R15With(=O)H, -C(=NR15)-NR16R17and OR15,

R4bselected from the group comprising H, optionally substituted C1-C12alkyl, optionally substituted C2-C12alkenyl, optionally substituted C2-C12quinil, optionally substituted C1-C12heteroalkyl, optionally substituted C3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optional samisen the th C 6-C18aryl, optionally substituted C1-C18heteroaryl, C(=O)R15C(=O)NR15R16C(=O)OR15or

R4aand R4btaken together with the nitrogen atom to which they are attached, form an optional substituted heterocyclic part, or

one of R4aand R4btaken together with any one of R13or R14forms optional substituted heterocyclic group;

each R5aand R5bindependently selected from the group including H, halogen, C1-C12alkyl, C1-C12hydroxyalkyl and C1-C12haloalkyl, or

one or more of R5aand Rbtaken together with one or more of R6, R7and R8and the atoms to which they are attached, form a part selected from the group including optional substituted With3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl;

R6, R7and R8each independently selected from the group including H, halogen, hydroxy, optionally substituted C1-C12alkyl, optionally substituted C2-C12alkenyl, optionally substituted C2-C12quinil, optionally substituted C1-C12 heteroalkyl, optionally substituted C1-C10heteroalkyl, optionally substituted C3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optionally substituted C6-C18aryl, optionally substituted C1-C18heteroaryl, optionally substituted amino, optionally substituted carboxy, C1-C12alkyloxy and optionally substituted thio, or

(a) taken together with the carbon atom to which they are attached, two or more of R6, R7and R8form part selected from the group including optional substituted With2-C12alkenyl, optionally substituted C3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl, or

(b) one or more of R6, R7and R8taken together with one or more of R5aand R5band the atoms to which they are attached, form a part selected from the group including optional substituted With3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl;

each R 9and R10independently selected from the group comprising N and optionally substituted C1-C12alkyl;

each R11and R12independently selected from the group comprising N and optionally substituted C1-C12alkyl;

each R13and R14independently selected from the group including H, halogen, HE1-C12alkyl, C6-C18aryl, C1-C12haloalkyl,1-C12hydroxyalkyl,1-C12alkyloxy and C1-C12haloalkoxy, or

taken together with the carbon atom to which they are attached, R13and R14form optional substituted With3-C12cycloalkyl, or optionally substituted C1-C12geterotsyklicescoe group, or

one of R13and R14taken together with one of R4aand R4bforms optional substituted heterocyclic group;

each R15, R16and R17independently selected from the group comprising H, optionally substituted C1-C12alkyl, optionally substituted C1-C12heteroalkyl, optionally substituted C3-C12cycloalkyl, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl, or

any two of R15, R16and R17taken together with the atoms which, to which they are attached, form an optional substituted cyclic group;

n is an integer selected from the group comprising 1, 2, 3, and 4;

q is an integer selected from the group comprising 0, 1, 2, 3, 4 and 5;

r is an integer selected from the group comprising 1, 2, 3, and 4;

s is an integer selected from the group comprising 1, 2, 3, and 4;

or its pharmaceutically acceptable salt or prodrug.

This invention also relates to pharmaceutical compositions comprising a compound of this invention with a pharmaceutically acceptable carrier, diluent or excipient.

A DETAILED DESCRIPTION of the INVENTION

In this description uses a number of expressions that are well known to the person skilled in the art. However, for the sake of clarity will be determined by the number of expressions.

As used here, the term "unsubstituted" means that there is no Deputy or that the only Deputy is hydrogen.

The expression "optional substituted", as used throughout the description, means that the group may or may not additionally be substituted or fused (so as to form a condensed polycyclic system), with one or more non-hydrogen replacing group. In certain embodiments of the implementation replaces the s group are one or more group independently selected from the group comprising halogen, =O, =S, -CN, -NO2, -CF3, -OCF3, alkyl, alkenyl, quinil, haloalkyl, haloalkyl, haloalkyl, heteroalkyl, cycloalkyl, cycloalkenyl, heteroseksualci, geteroseksualen, aryl, heteroaryl, cycloalkenyl, geterotsiklicheskikh, heteroallyl, arylalkyl, cycloalkenyl, geterotsiklicheskikh, arylalkyl, heteroaromatic, cycloalkylcarbonyl, geterotsiklicheskikh, arylheteroacetic, heterotrimetallic, hydroxy, hydroxyalkyl, alkyloxy, alkyloxyalkyl, alkyloxyalkyl, alkyloxyalkyl, alkyloxyaryl, alkyloxyalkyl, allyloxycarbonyl, alkylaminocarbonyl, alkenylacyl, alkyloxy, cycloalkane, cycloalkenyl, heterocyclizations, heterocyclizations, aryloxy, phenoxy, benzyloxy, heteroaromatic, arylalkyl, amino, alkylamino, acylamino, aminoalkyl arylamino, sulfonylamino, sulfonylamino, sulfonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, sulfinil, alkylsulfonyl, arylsulfonyl, aminosulphonylphenyl, -C(=O)HE, -C(=O)Ra, -C(=O)ORaC(=O)NRaRbC(=NOH)RaC(=NRa)NRbRc, NRaRb, NRaC(=O)Rb, NRaC(=O)ORb, NRaC(=O)NRbRc, NRaC(=NRb)NRcRd, NRaSO2Rb, -SR a, SO2NRaRb, -ORa, OC(=O)NRaRb, OC(=O)Raand acyl,

where Ra, Rb, Rcand Rdeach independently selected from the group including H, C1-C12alkyl, C1-C12haloalkyl, C2-C12alkenyl, C2-C12quinil,1-C10heteroalkyl,3-C12cycloalkyl,3-C12cycloalkenyl,1-C12heteroseksualci,1-C12geteroseksualen,6-C18aryl, C1-C18heteroaryl and acyl, or any two or more of Ra, Rb, Rcand Rdtaken together with the atoms to which they are attached, form a heterocyclic ring system with 3 to 12 ring atoms.

In one embodiment, each of the optional Deputy independently selected from the group comprising: halogen, =O, =S, -CN, -NO2, -CF3, -OCF3, alkyl, alkenyl, quinil, haloalkyl, haloalkyl, haloalkyl, heteroalkyl, cycloalkyl, cycloalkenyl, heteroseksualci, geteroseksualen, aryl, heteroaryl, hydroxy, hydroxyalkyl, alkyloxy, alkyloxyalkyl, alkyloxyaryl, alkyloxyalkyl, alkenylacyl, alkyloxy, cycloalkane, cycloalkenyl, heterocyclizations, heterocyclizations, aryloxy, heteroaromatic, arylalkyl, heteroallyl, arylalkyl, amino, alkylamino, and is ylamino, aminoalkyl, arylamino, sulfonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, aminoalkyl, -COOH, -SH and acyl.

Examples of particularly suitable optional substituents include F, Cl, Br, I, CH3CH2CH3HE co3, CF3, OCF3, NO2, NH2and CN.

In the definitions of a number of deputies below found that "the group may be a terminal group or a bridging group. It is assumed that this means that the use of the expression has to include the situation where the group is a connecting link between two other parts of the molecule, and where it is a terminal part. The use of an alkyl as an example, some publications use the term "alkylene for bridge group, and therefore, in these other publications there is a distinction between the expressions "alkyl" (terminal group) and alkylen" (bridge group). In this application not made such a distinction, and most groups can be either a bridge group or terminal group.

Multiple expressions begin with the index register, showing a number of carbon atoms present in the part. For example, the index register "C1-C6" before the expression "alkyl" indicates that the alkyl h is the terrain has 1-6 carbon atoms. In addition, the index register "C1-C18" before the expression "heteroaryl" shows that the heteroaromatic ring may have 1-18 carbon atoms in the composition of the total number of atoms in the ring system.

"Acyl" means R-C(=O)- group in which the R group can be an alkyl, cycloalkyl, geterotsyklicescoe, aryl or heteroaryl group, as defined here. Examples of acyl include acetyl and benzoyl. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via a carbonyl carbon.

"Acylamino" means R-C(=O)-NH-group in which the R group can be an alkyl, cycloalkyl, geterotsyklicescoe, aryl or heteroaryl group, as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via the nitrogen atom.

"Alkenyl" as a group or part of a group means an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and which may be straight or branched, preferably 2-14 carbon atoms, more preferably 2-12 carbon atoms, most preferably 2-6 the volume of carbon in the normal chain. A group can contain multiple double bonds in the normal chain and the orientation around each is independently E or Z. Approximate alkeneamine groups include, but are not limited to, ethynyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl and nonanal. The group may be a terminal group or a bridging group.

"Alkenylacyl" refers to alkenyl-O-group in which alkenyl is such as defined here. The preferred alkenylamine groups represent a1-C6alkenylamine group. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via an oxygen atom.

"Alkyl" as a group or part of a group refers to a straight or branched aliphatic hydrocarbon group, preferably C1-C14alkyl, more preferably C1-C10alkyl, most preferably C1-C6if not stated otherwise. Examples of suitable straight and branched C1-C6alkyl substituents include methyl, ethyl, n-propyl, 2-propyl, n-butyl, sec-butyl, tert-butyl, hexyl and the like. The group may be a terminal group or a bridging group.

"Alkylamino" includes, monoalkylamines, and the dial is ylamino, if not mentioned explicitly. "Monoalkylamines" means alkyl-NH-group in which alkyl is such as defined here. "Dialkylamino" means (alkyl)2N-group in which each alkyl may be the same or different, and each is such as defined here for alkyl. The alkyl group preferably represents C1-C6alkyl group. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via the nitrogen atom.

"Alkylaminocarbonyl" refers to a group of the formula (Alkyl)x(H)yNC(=O)-, in which x represents 1 or 2 and the sum of x+y=2. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via a carbonyl carbon.

"Alkyloxy" refers to alkyl-O-group in which alkyl is such as defined here. Preferably alkyloxy represents a C1-C6alkyloxy. Examples include, but are not limited to, methoxy, ethoxy. The group may be a terminal group or a bridging group.

"Alkyloxyalkyl" refers to alkyloxy-alkyl-group in which alkyloxy and alkyl parts are such that ka is defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through an alkyl group.

"Alkyloxyaryl" refers to alkyloxy-aryl group in which alkyloxy and aryl part are as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through an aryl group.

"Allyloxycarbonyl" refers to alkyl-O-C(=O)-group in which alkyl is such as defined here. The alkyl group preferably represents C1-C6alkyl group. Examples include, but are not limited to, methoxycarbonyl and etoxycarbonyl. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via a carbonyl carbon.

"Alkyloxyalkyl" refers to alkyloxy-cycloalkyl-group, in which alkyloxy and cycloalkyl parts are such as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through cycloalkyl gr the foam.

"Alkyloxyalkyl" refers to alkyloxy-heteroaryl-group, in which alkyloxy and heteroaryl part are as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through a heteroaryl group.

"Alkyloxyalkyl" refers to alkyloxy-heteroseksualci-group, in which alkyloxy and heterocytolysine parts are such as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through geterotsyklicescoe group.

"Alkylsulfonyl" means alkyl-S(=O)-group, which is such as defined here. The alkyl group preferably represents C1-C6alkyl group. Approximate alkylsulfonyl groups include, but are not limited to, methylsulfinyl and ethylsulfinyl. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through a sulfur atom.

"Alkylsulfonyl" refers to alkyl-S(=O)2-group in which alkyl is such as defined above. Alkyl g is the SCP preferably represents C 1-C6alkyl group. Examples include, but are not limited to, methylsulphonyl and ethylsulfonyl. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through a sulfur atom.

"Quinil" as a group or part of a group means an aliphatic hydrocarbon group containing a carbon-carbon triple bond, and which may be straight or branched, preferably having 2-14 carbon atoms, more preferably 2-12 carbon atoms, more preferably 2-6 carbon atoms in the normal chain. Exemplary patterns include, but are not limited to, ethinyl and PROPYNYL. The group may be a terminal group or a bridging group.

"Alkyloxy" refers to quinil-O-group in which quinil is such as defined here. The preferred alkyloxy group represents a C1-C6alkyloxy group. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via an oxygen atom.

"Aminoalkyl" means the NH2-alkyl-group in which the alkyl group is as defined here. The group may be a terminal GRU is PU or bridge group. If the group is a terminal group, it is connected with the remainder of the molecule through an alkyl group.

"Aminosulfonyl" means the NH2-S(=O)2-group. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through a sulfur atom.

"Aryl" as a group or part of a group means (i) optional substituted monocyclic or fused polycyclic, aromatic carbon cycle (ring structure having ring atoms, all of which are carbon), preferably having 5 to 12 atoms in the ring. Examples of aryl groups include phenyl, naphthyl and the like; (ii) the optional substituted partially saturated bicyclic aromatic carbocyclic portion, in which phenyl and C5-7cycloalkyl or C5-7cycloalkenyl group merged together to form a cyclic structure, such as tetrahydronaphthyl, indenyl or indanyl. The group may be a terminal group or a bridging group. Basically aryl group represents a C6-C18aryl group.

"Arylalkyl" means aryl-alkenyl-group in which the aryl and alkenyl are as defined here. Approximate arylalkyl group include phenylalkyl. GRU is PA can be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through alkenylphenol group.

"Arylalkyl" means an aryl-alkyl-group in which the aryl and alkyl parts are such as defined here. Preferred arylalkyl groups contain C1-5alkyl part. Approximate arylalkyl groups include benzyl, phenethyl, 1-naphthalenethiol and 2-naphthalenethiol. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through an alkyl group.

"Arylalkyl" refers to aryl-alkyl-O-group in which alkyl and aryl are as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via an oxygen atom.

"Arylamino" includes, monoarylamino, diarylamino, if not mentioned explicitly. Monoarylamino means a group of the formula N-in which aryl is such as defined here. Diarylamino means a group of the formula (aryl)2N-, where each aryl may be the same or different, and each is such as defined here for aryl. The group may be a terminal group or a bridging group is at. If the group is a terminal group, it is connected with the remainder of the molecule via the nitrogen atom.

"Arylheteroacetic" means aryl-heteroalkyl-group, in which aryl and heteroalkyl parts are such as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through heteroalkyl group.

"Aryloxy" refers to aryl-O-group, in which aryl is such as defined here. Preferably aryloxy represents a C6-C18aryloxy, more preferably6-C10aryloxy. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via an oxygen atom.

"Arylsulfonyl" means an aryl-S(=O)2-the group in which the aryl group is as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through a sulfur atom.

"Connection" is a connection between atoms in a compound or molecule. Communication can be a single bond, double bond or triple bond.

"Cyclic group" refers to saturated, partially unsaturated, or fully unsaturated monocyclic, bicyclic or polycyclic ring system. Examples of cyclic groups include cycloalkyl, cycloalkenyl and aryl.

"Cycloalkenyl" means a non-aromatic monocyclic or cyclical ring system containing at least one carbon-carbon double bond and preferably having 5 to 10 carbon atoms in the ring. Exemplary monocyclic cycloalkenyl rings include cyclopentenyl, cyclohexenyl or cycloheptenyl. Cycloalkenyl group may be substituted by one or more groups of deputies. The group may be a terminal group or a bridging group.

"Cycloalkyl" refers to a saturated monocyclic or fused or Spiro polycyclic, carbon cycle, preferably containing 3-9 carbon in the ring, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like, unless otherwise specified. It includes monocyclic system, such as cyclopropyl and cyclohexyl, bicyclic system such as decalin, and polycyclic systems, such as adamantane. The group may be a terminal group or a bridging group.

"Cycloalkenyl" means cycloalkyl-alkyl-group in which cycloalkyl and the alkyl part ablauts is such, as defined here. Approximate monocyclohexyl group include cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl and cycloheptylmethyl. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through an alkyl group.

"Cycloalkylcarbonyl" means cycloalkyl-alkenyl-group, in which cycloalkyl and Alchemilla parts are such as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through alkenylphenol group.

"Cycloalkylcarbonyl" means cycloalkyl-heteroalkyl-group, in which cycloalkyl and heteroalkyl parts are such as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through heteroalkyl group.

"Cycloalkane" refers to cycloalkyl-O-group in which cycloalkyl is such as defined here. Preferably cycloalkane represents a C1-C6cycloalkane. Examples include, but are not limited to, cyclopropane, CYCLOBUTANE. Groupabout be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via an oxygen atom.

"Cycloalkenyl" refers to cycloalkenyl-O-group in which cycloalkenyl is such as defined here. Preferably cycloalkenyl represents a C1-C6cycloalkenyl. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via an oxygen atom.

"Haloalkyl" refers to an alkyl group, as defined here, in which one or more hydrogen atoms replaced with a halogen atom selected from the group comprising fluorine, chlorine, bromine and iodine. Haloalkaline group typically has the formula CnH(2n+1-m)Xmwhere each X is independently selected from the group comprising F, Cl, Br and I. In groups of this type n is usually 1-10, more preferably 1-6, most preferably 1-3. m usually is 1-6, preferably 1-3. Examples of haloalkyl include vermeil, deformity and trifluoromethyl.

"Haloalkyl" refers to alkenylphenol group, as defined here, in which one or more of the hydrogen atoms replaced by halogen atom, independently selected from the group comprising F, Cl, Br and I.

"Haloalkyl" refers to alkenylphenol group, as defined ZV is camping, in which one or more hydrogen atoms replaced with a halogen atom, independently selected from the group comprising F, Cl, Br and I.

"Halogen is chlorine, fluorine, bromine or iodine.

"Heteroalkyl" refers to an alkyl group with straight or branched chain, preferably having 2-14 carbon, more preferably 2-10 carbon chain, one or more of which is substituted by a heteroatom selected from S, O, P and N. the Approximate heteroalkyl include alkyl ethers, secondary and tertiary alkyl amines, amides, alkyl sulfides and the like. The group may be a terminal group or a bridging group.

"Heteroaryl" or individual, or as part of another group refers to groups containing an aromatic ring (preferably a 5 or 6 membered aromatic ring containing one or more heteroatoms as ring atoms in the aromatic ring with the remainder of the ring atoms constituting the carbon atoms. Suitable heteroatoms include nitrogen, oxygen and sulfur. Examples of heteroaryl include thiophene, benzothiophene, benzofuran, benzimidazole, benzoxazole, benzothiazole, benzisothiazole, oil[2,3-b]thiophene, furan, isoindolines, santolan, enoxacin, pyrrole, imidazole, pyrazole, pyridine, pyrazin, pyrimidine, pyridazine, tetrazole, indole, isoindole, 14-indazole, purine, quinoline, isoquinoline, phthalazine, afterid is h, cinoxacin, cinnoline, carbazole, phenanthridine, acridine, fenesin, thiazole, isothiazol, phenothiazines, oxazol, isooctanol, furazan, phenoxazine, 2-, 3 - or 4-pyridyl, 2-, 3-, 4-, 5 - or 8-chinolin, 1-, 3-, 4 - or 5-ethenolysis 1-, 2 - or 3-indolyl, and 2 - or 3-thienyl. The group may be a terminal group or a bridging group.

"Heteroaromatic" means heteroaryl-alkyl group in which the heteroaryl and alkyl parts are such as defined here. Preferred heteroallyl groups include the lower alkyl part. Approximate heteroallyl group include pyridylmethyl. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through an alkyl group.

"Heteroaromatic" means heteroaryl-alkenyl-group in which the heteroaryl and Alchemilla parts are such as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through alkenylphenol group.

"Heterotrimetallic" means heteroaryl-heteroalkyl-group in which the heteroaryl and heteroalkyl parts are such as defined here. The group may make with the terminal Oh group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through heteroalkyl group.

"Heteroaromatic" refers to heteroaryl-O-group in which heteroaryl is such as defined here. Preferably heteroaromatic represents a C1-C12heteroaromatic. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via an oxygen atom.

"Heterocyclic" refers to a saturated, partially unsaturated, or fully unsaturated monocyclic, bicyclic or polycyclic ring system containing at least one heteroatom selected from the group comprising nitrogen, sulfur and oxygen as ring atoms. Examples of heterocyclic parts include heteroseksualci, geteroseksualen and heteroaryl.

"Geteroseksualen" refers to heteroseksualci, as defined here, but containing at least one double bond. The group may be a terminal group or a bridging group.

"Heteroseksualci" refers to a saturated monocyclic, bicyclic or polycyclic ring containing at least one heteroatom selected from nitrogen, sulfur, oxygen, preferred is part 1-3 heteroatoms, at least one ring. Each ring represents preferably 3-10 membered, more preferably 4-7 membered. Examples of suitable geterotsiklicheskikh substituents include pyrrolidyl, tetrahydrofuryl, tetrahydrofuranyl, piperidyl, piperazin, tetrahydropyranyl, morpholino, 1,3-diazepan, 1,4-diazepan, 1,4-oxazepan and 1,4-Ossetian. The group may be a terminal group or a bridging group.

"Geterotsiklicheskikh" refers to heteroseksualci-alkyl-group in which heterocytolysine and alkyl parts are such as defined here. Approximate geterotsiklicheskikh groups include (2-tetrahydrofuryl)methyl, (2-tetrahydrofuranyl) methyl. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through an alkyl group.

"Geterotsiklicheskikh" refers to heteroseksualci-alkenyl-group, in which heterocytolysine and Alchemilla parts are such as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through alkenylphenol group.

"Geterotsiklicheskikh" means heteroseksualci-g is tetraalkyl group in which heterocytolysine and heteroalkyl parts are such as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through heteroalkyl group.

"Heterocyclizations" refers to heteroseksualci-O-group in which heteroseksualci is such as defined here. Preferably Heterocyclizations represents a C1-C6heterocyclizations. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via an oxygen atom.

"Heterocyclizations" refers to geteroseksualen-O-group in which geteroseksualen is such as defined here. Preferably Heterocyclizations represents a C1-C6heterocyclizations. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via an oxygen atom.

"Hydroxyalkyl" refers to an alkyl group, as defined here, in which one or more of the hydrogen atoms replaced IT with the group. Hydroxyalkyl group typically named the em formula C nH(2n+1-x)(OH)x. In groups of this type, n is typically 1-10, more preferably 1-6, most preferably 1-3. x typically is 1-6, preferably 1-3.

"Lower alkyl" as a group means, unless otherwise specified, an aliphatic hydrocarbon group which may be straight or branched with 1-6 carbon atoms in the chain, more preferably 1-4 carbons, such as methyl, ethyl, propyl (n-propyl or isopropyl) or butyl (n-butyl, isobutyl or tertiary-butyl). The group may be a terminal group or a bridging group.

"Sulfinil" means R-S(=O)-group in which the R group can be a HE, alkyl, cycloalkyl, geterotsyklicescoe; aryl or heteroaryl group, as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through a sulfur atom.

"Sulfonylamino" means R-S(=O)-NH-group in which the R group can be a HE, alkyl, cycloalkyl, geterotsyklicescoe; aryl or heteroaryl group, as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through tomasita.

"Sulfonyl" means R-S(=O)2-the group in which the R group can be a HE, alkyl, cycloalkyl, geterotsyklicescoe; aryl or heteroaryl group, as defined here. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule through a sulfur atom.

"Sulfonylamino" means R-S(=O)2-NH-group. The group may be a terminal group or a bridging group. If the group is a terminal group, it is connected with the remainder of the molecule via the nitrogen atom.

It is clear that is included in the family of compounds of formula (I) are isomeric forms including diastereoisomers, enantiomers, tautomers and geometric isomers in "E" or "Z" configuration isomer or a mixture of E and Z isomers. It is also clear that some isomeric forms, like the diastereomers, enantiomers and geometric isomers can be divided physical and/or chemical methods and experts in this technology.

Some of the compounds disclosed embodiments may exist as single stereoisomers, racemates, and/or mixtures of enantiomers and/or diastereomers. It is assumed that all such single stereoisomers, racemates and mixtures thereof nahodatsa is in the scope of the subject invention, described and claimed.

This invention includes all pharmaceutically acceptable isotopically-labeled compounds of formula (I)where one or more atoms have the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number usually found in nature.

Examples of isotopes suitable for inclusion in the compounds of this invention include isotopes of hydrogen, such as2H and3H carbon, such as11C,13C and14With chlorine, such as36Cl, fluorine, such as18F, iodine, such as123I and125I, of nitrogen, such as13N and15N, oxygen, such as15Oh,17O and18Oh, phosphorus, such as32P and sulfur, such as35S.

Certain isotopically-labeled compounds of formula (I), for example, those that include a radioactive isotope, applicable when studying the distribution of drugs and/or substrate tissue. Radioactive isotopes tritium, i.e3H, and carbon-14, i.e14With, especially applicable for this purpose due to their ease of incorporation and rapid means of detection.

Replacement of heavier isotopes such as deuterium, i.e2N may provide certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo in EMA half-life or reduced dosage requirements, and, therefore, may be preferred in some circumstances.

Replacement positron emitting isotopes, such as11C,18F,15O and13N, may be applicable in studies of Positron Emission Tomography (PET) to verify the employment of the receptor substrate.

Isotopically labeled compounds of formula (I) can generally be prepared by standard methods known to the person skilled in the art or by processes analogous to those described in the accompanying Examples and Preparations using appropriate isotopically-labeled reagents instead of unlabeled reagent used previously.

Additionally, the Formula (I) is intended to cover, if necessary, solvated and nonsolvated form compounds. Thus, each formula includes compounds having the structure, including hydrated and UN-hydrated form.

The expression "pharmaceutically acceptable salts" refers to salts that retain the desired biological activity of the above-identified compounds, and include pharmaceutically acceptable salts of accession of the acid and the salt of the attaching base. Suitable pharmaceutically acceptable salts of accession of the acid compounds of formula (I) can be prepared from an inorganic acid or from an organic KIS is the notes. Examples of such inorganic acids are hydrochloric, sulfuric and phosphoric acid. Suitable organic acids can be selected from aliphatic, cycloaliphatic, aromatic, heterocyclic carboxylic and sulfonic classes of organic acids, examples of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, fumaric, maleic, alkylsulfonate, arylsulfonate. For more information pharmaceutically acceptable salts can be found in Remington''s Pharmaceutical Sciences, 19th Edition, Mack Publishing Co., Easton, PA 1995. In the case of substances that are solids, the person skilled in the art it is clear that patentable compounds, substances, and salts may exist in different crystal or polymorphic forms, all of which must be in the scope of the present invention and provided formulas.

"Prodrug" means a compound which is converted into the compound of formula (I) in a biological system, usually metabolic means (e.g. by hydrolysis, recovery or oxidation). For example, the ester Prodrug of compounds of formula (I)containing a hydroxyl group, can be transformed by hydrolysis in vivo to the original molecule. Suitable esters is of soedinenii formula (I), containing a hydroxyl group, are for example acetates, citrates, lactates, tartratami, malonate, oxalates, salicylates, propionate, succinate, fumarate, maleate, methylene-bis-β-hydroxynaphthoate, gentisate, isethionate, di-p-toluoyltartaric, methansulfonate, econsultancy, bansilalpet, p-toluensulfonate, cyclohexylsulfamate and salt Hinn acid. As another example, the ester Prodrug of compounds of formula (I)containing carboxypropyl, can be converted by hydrolysis in vivo to the original molecule. (Examples of ester prodrugs are those as described F.J.Leinweber, Drug Metab. Res., 18:379, 1987). Similarly, acyl prodrug compounds of formula (I)containing an amino group can be converted by hydrolysis in vivo to the original molecule (most of the examples of prodrugs for these and other functional groups, including amines described in Prodrugs: Challenges and Rewards (Parts 1 and 2); Ed V.Stella, R.Borchardt, M.Hageman, R.Oliyai, H.Maag and J Tilley; Springer, 2007).

As with any group of structurally related compounds, which have a certain usefulness, certain embodiments of the variables of the compounds of formula (I)are particularly suitable for the final application.

In the compounds of this invention Y is a group of the formula -(CR9R10)n-. In one embodiment, the done by the means of the invention n is 1 and Y is-CR 9R10-. In another embodiment of the invention n is 2 and Y is-CR9R10CR9R10-.

In one embodiment, compounds of the present invention, each R9and R10independently selected from N and CH3. In one particular embodiment, R9and R10both are N. Accordingly, in one embodiment of this invention Y is CH2-. In another embodiment of this invention Y is-CH2CH2-. In another embodiment of this invention Y is-C(CH3)2-.

In one embodiment of this invention R2represents N or C1-C6alkyl. In a particular embodiment, R2represents N.

In one embodiment, compounds of this invention R3represents N or C1-C6alkyl. In a particular embodiment, R3represents N.

In one embodiment, compounds of the present invention X is chosen from the group comprising-C(=O)- and -(CR11R12)s-. In one particular embodiment, X represents-C(=O)-. In one embodiment of the present invention, where X is present is employed, a -(CR 11R12)s-, s represents 1. In another embodiment of the present invention, where X represents a -(CR11R12)s-, s represents 2. In one form of each of these embodiments, R11and R12each independently selected from the group comprising N and C1-C6alkyl. In a specific embodiment, both R11and R12represent H, and s represents 1 so that X represents-CH2-.

In one embodiment, compounds of this invention Y is CH2, R2represents H, R3represents H, X represents-C(=O)-. This provides the compounds of formula (II).

,

where R1, R4a, R4b, R5a, R5b, R6, R7, R8, Z and r are as defined for formula (I).

In one embodiment, compounds of the present invention and in particular the compounds of formula (I) and formula (II) r is chosen from the group comprising 1, 2, 3 and 4. In one particular embodiment, r represents 1. In another particular embodiment, r is 2. In another particular embodiment, r is a 3. In another specific embodiment, g is a 4.

In one embodiment, compounds of the present invention and in particular the compounds of formula (I) and formula (II) R5aand R5bindependently selected from N and C1-C6the alkyl. In one embodiment, R5aand R5beach independently selected from N and CH3. In one particular embodiment, R5aand R5bboth are N. In yet another embodiment, at least one of R5aand R5btaken together, at least one of R6, R7and R8and the atoms to which they are attached, form an optional substituted cycloalkyl group. In one particular embodiment, at least one of R5aand R5btaken together, at least one of R6, R7and R8and the atoms to which they are attached, forms a tsiklogeksilnogo group.

In one embodiment, compounds of this invention Y is CH2, R2represents H, R3represents H, R5aand R5brepresent H, and X represents-C(=O)-, and r represents 1. This provides the compounds of formula (III).

,

where R1, R4a, R4b, R6, R7, R8and Z are as defined for formula (I).

In one var is the ante implementation of the compounds of this invention and, in particular, compounds of formula (I), (II) and (III), R7represents N.

In one embodiment, compounds of the present invention, Y is CH2, R2represents H, R3represents H, R5aand R5brepresent H, R7represents H, X represents-C(=O)-, and r represents 1. This provides the compounds of formula (IV).

,

where R1, R4a, R4b, R6, R8and Z are as defined for formula (I).

In the compounds of the present invention Z represents a group of formula -(CR13R14)q-. In one embodiment, compounds of the present invention and in particular compounds of formula (I), formula (II), formula (III), formula (IV) R13and R14independently selected from H and C1-C6the alkyl. In one embodiment, R13and R14each independently selected from N and CH3. In one particular embodiment, R13and R14both are N. Accordingly, in one particular embodiment, Z is a group -(CH2)q-. In yet another embodiment, at least one of R13and R14taken together, at least one of R4aand R4band the atoms to which they are attached, form a optional amestoy geterotsyklicescoe group.

In one embodiment, compounds of the present invention and in particular compounds of the formula (IV) q is an integer selected from the group comprising 0, 1, 2, 3, 4 and 5. In one particular embodiment, q represents 1. In another specific embodiment, q represents 2, in another embodiment, q represents 3, and in yet another embodiment, q is a 4. In cases where R13and R14both represent N, this provides the compounds of formula (IVa), (IVb), (IVc) and (IVd), respectively.

,

where R1, R4a, R4b, R6and R8are as defined for formula (I).

,

where R1, R4a, R4b, R6and R8are as defined for formula (I).

,

where R1, R4a, R4b, R6and R8are as defined for formula (I).

,

where R1, R4a, R4b, R6and R8are as defined for formula (I).

In one embodiment of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd), R6and R8each independently selected from the group comprising N, FAK is litative substituted C 1-C12alkyl, optionally substituted C2-C12alkenyl, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl.

In one embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd), R6and R8each independently selected from the group including optional substituted C1-C12alkyl, optionally substituted C2-C12alkenyl, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl.

In one embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd), R6and R8each independently selected from the group including optional substituted C2-C12alkyl, optionally substituted C2-C12alkenyl, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl.

In one particular embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd) R6selected from the group including ethyl, 2,2,2-triptorelin, isopropyl, Isopropenyl, propyl, 2-ethylpropyl, 3,3-dimethylpropyl, butyl, 2-methylbutyl, isobutyl, 3,3-dimethyl who util, 2-ethylbutyl, pentyl, 2-methylpentyl, optionally substituted phenyl and optionally substituted C1-C5heteroaryl.

In one particular embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd) R6is an optional substituted phenyl, or optionally substituted C1-C18heteroaryl.

In one particular embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd) R8selected from the group including ethyl, 2,2,2-triptorelin, isopropyl, Isopropenyl, propyl, 2-ethylpropyl, 3,3-dimethylpropyl, butyl, 2-methylbutyl, isobutyl, 3,3-dimethylbutyl, 2-ethylbutyl, pentyl, 2-methylpentyl, optionally substituted phenyl and optionally substituted C1-C5heteroaryl.

In one particular embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd) R8represents methyl, ethyl, phenyl, or optionally substituted C1-C5heteroaryl.

In one particular embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd) R6, R7and R8taken together with the carbon atom to which they are attached is s, form part selected from the group including optional substituted With2-C12alkenyl, optionally substituted C3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl.

In one particular embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd) R6, R7and R8taken together with the carbon atom to which they are attached, form an optional substituted With6-C18aryl group.

In one particular embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd) R6, R7and R8taken together with the carbon atom to which they are attached, form a disubstituted phenyl group. In one embodiment, disubstituted phenyl group represents a 2,4-disubstituted Hairdryer-1-ilen group or a 3,5-disubstituted Hairdryer-1-ilen group. Wide variety of substituents can be present at disubstituted phenyl group as defined above. Examples of particularly suitable substituents include, but are not limited to, F, Br, Cl, methyl, trifluoromethyl, ethyl, 2,2,2-triptorelin, isopr the saws, propyl, 2-ethyl-propyl, 3,3-dimethyl-propyl, butyl, isobutyl, 3,3-dimethyl-butyl, 2 - ethyl-butyl, pentyl, 2-methyl-pentyl, Penta-4-enyl, hexyl, heptyl, octyl, phenyl, NH2, cyano, phenoxy, hydroxy, methoxy, ethoxy, methylenedioxy, pyrrol-1-yl and 3,5-dimethyl-pyrazole-1-yl. In one particular embodiment, disubstituted phenyl group represents a 3,5-dichlorophen-1-ilen group.

In one embodiment, compounds of the present invention and, in particular, compounds of the formula (IV), (IVa, (IVb), (IVc) and (IVd), R4aselected from the group including H, C(=NH)NH2, C(=NH)N(CH3)2, C(=NH)NHCH3, C(=NH)N, -C(=O)CH3-C(=O)cyclohexyl, CH3CH2CH3CH2CH2CH3CH(CH3)2CH2CH2CH2CH3CH(CH3)CH2CH3CH2CH(CH3)2, (CH3)3cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, benzyl and phenyl or halogenated derivative.

In one embodiment, compounds of the present invention and, in particular, compounds of the formula (IV), (IVa), (IVb), (IVc) and (IVd), R4bselected from the group comprising H, CH3CH2CH3CH2CH2CH3CH(CH3)2CH2CH2CH2CH3CH(CH3)CH2CH3CH2CH(CH3)2, (CH3 3cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, benzyl and phenyl or halogenated derivative.

In one embodiment, compounds of the present invention and, in particular, compounds of the formula (IV), (IVa), (IVb), (IVc) and (IVd), R4aand R4btaken together with the nitrogen atom to which they are attached, form an optional substituted cyclic group. Optional substituted cyclic group may be an optional substituted With2-C12geterotsyklicescoe group, optionally substituted C1-C12geterotsyklicescoe group, or optionally substituted C1-C18heteroaryl group. In one particular embodiment, R4aand R4btaken together with the nitrogen atom to which they are attached, form an optional substituted C2-C12geterotsyklicescoe group.

In one embodiment of the present invention and, in particular, compounds of the formula (IV), (IVa), (IVb), (IVc) and (IVd) R4aand R4btaken together with the nitrogen atom to which they are attached, form an optional substituted geterotsyklicescoe group selected from the group comprising piperidine-1-yl, pyrrolidin-1-yl, azetidin-1-yl, morpholine-4-yl, piperazine-1-yl and azepin-1-yl.

Specific examples NR4aR4binclude:

In one embodiment of the present invention and, in particular, compounds of the formula (IV) one of R4aand R4btaken together with the nitrogen atom to which it is attached, and one of R13and R14and the carbon atom to which it is attached, form an optional substituted With2-C12geterotsyklicescoe group.

In one embodiment of the present invention and, in particular, compounds of the formula (IV) one of R4aand R4btaken together with the nitrogen atom to which it is attached, and one of R13and R14and the carbon atom to which it is attached, form optional samewe the s 2-C12geterotsyklicescoe group selected from the group comprising piperidinyl, pyrrolidinyl, azetidine, morpholine, piperazinil and azepane.

Specific examples of such side chain ZN(R4a)(R4bso cyclization between one or R4aand R4band one of R13and R14include:

In one embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd), R1selected from the group including optional substituted With2-C12alkenyl, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl.

In one embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb), (IVc) and (IVd), R1is an optional substituted With6-C18aryl. With6-C18the aryl may be a monocyclic, bicyclic or polycyclic part. In certain embodiments of the exercise With6-C18aryl represents monocyclic part. In certain embodiments of the exercise With6-C18aryl represents a bicyclic part.

In one particular embodiment, the implementation of the ing R 1is an optional substituted With6-C18aryl selected from the group including optional substituted phenyl, biphenyl and optionally substituted naphthyl. Parts can be unsubstituted or can be substituted by one or more optional substituents. A large number of optional substituents can be used, as defined above. Examples of particularly suitable optional substituents include, but are not limited to, F, Br, Cl, methyl, trifluoromethyl, ethyl, 2,2,2-triptorelin, isopropyl, propyl, 2-ethyl-propyl, 3,3-dimethyl-propyl, butyl, isobutyl, 3,3-di methyl-butyl, 2-ethyl-butyl, pentyl, 2-methyl-pentyl, Penta-4-enyl, hexyl, heptyl, octyl, phenyl, NH2, cyano, phenoxy, hydroxy, methoxy, ethoxy, pyrrol-1-yl and 3,5-dimethyl-pyrazole-1-yl.

The substituents can be located in any substitutable position around aryl rings that are available for replacement, as will be clear to the person skilled in the art. Examples of suitable optional substituted phenyl compounds include, but are not limited to, 2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 2-trifluoromethyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-bromo-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 4-hydroxy-phenyl, 4-phenyl-phenyl, 4-methyl-phenyl, 2,4-dichloro-phenyl, 3,4-dichloro-phenyl, 2,5-dichloro-FeNi is, 2,6-debtor-phenyl, 2-chloro-6-fluoro-phenyl, 3-fluoro-4-chloro-phenyl, 3-methyl-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 3-chloro-4-methyl-phenyl, 2-hydroxy-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 4-ethoxy-phenyl, 3-phenoxy-phenyl, 4-phenoxy-phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 4-isopropyl-phenyl, 4-cyano-phenyl 3,4-dimethyl-phenyl, 2,4-dimethyl-phenyl, 4-tert-butyl-phenyl, 2,4-dimethoxy-phenyl and 3,4-methylenedioxy-phenyl.

When R1is an optional substituted biphenyl, the point of attachment of R1the remainder of the molecule can be 2-, 3 - or 4 - position relative to the attachment point of the second phenyl ring. As such, the biphenyl can be an optional substituted bifen-2-yl, or optionally substituted bifen-3-yl, or optionally substituted bifen-4-yl. Basically optional substituted biphenyl is an optional substituted bifen-4-yl. Optional substituted biphenyl can be substituted in any suitable position.

When R1is an optional substituted naphthyl, the point of attachment of R1the remainder of the molecule can be in 1 or 2 position. As such, the naphthyl may be an optional substituted naphthas-1-yl, or optionally substituted naphthas-2-yl. Basically optional substituted naphthyl is an optional substituted naphthas-2-yl. The Department is actively substituted naphthyl may be substituted in any suitable position. Examples of suitable optional substituted naphthas-2-silts include, but are not limited to, 6-fluoro-naphthas-2-yl, 6-bromo-naphthas-2-yl, 6-chloro-naphthas-2-yl, 1-methoxy-naphthas-2-yl, 3-methoxy-naphthas-2-yl, 6-methoxy-naphthas-2-yl, 1-hydroxy-naphthas-2-yl and 6-amino-naphthas-2-yl.

In one embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II), (111), (IV), (IVa), (IVb), (IVc) and (IVd) R1is an optional substituted With1-C18heteroaryl. With1-C18heteroaryl may be a monocyclic, bicyclic or polycyclic part. In certain embodiments of the exercise With1-C18heteroaryl represents a monocyclic part. In certain embodiments of the implementation of C1-C18heteroaryl represents a bicyclic part. Examples of suitable heteroaryl parts include, but are not limited to, indole-2-yl, indol-3-yl, the quinoline-2-Il quinoline-3-yl, isoquinoline-3-yl, cinoxacin-2-yl, benzo[b]furan-2-yl, benzo[b]thiophene-2-yl, benzo[b]thiophene-5-yl, thiazol-4-yl, benzimidazole-5-yl, benzotriazol-5-yl, furan-2-yl, benzo[d]thiazol-6-yl, pyrazole-1-yl, pyrazole-4-yl and thiophene-2-yl. They can also be optional substituted, as discussed above.

In one particular embodiment, compounds of the present invention and, in particular, compounds of formula (I), (II) (III), (IV), (IVa), (IVb),(IVc) and (IVd) R 1is an optional substituted With2-C12alkenyl. Optional substituted alkenyl may contain one or more double bonds with each of the double bonds, being independent in the E or Z configuration. In one embodiment of the present invention of alkenyl contains one double bond, which is in the E configuration.

In one particular form of this variant implementation of R1is an optional substituted With2-C12alkenyl formula:

,

R1aselected from the group including H, halogen and optionally substituted C1-C12alkyl;

R1band R1ceach independently selected from the group including H, halogen, optionally substituted C1-C12alkyl, optionally substituted C2-C12alkenyl, optionally substituted C2-C12quinil, optionally substituted C2-C12heteroalkyl, optionally substituted C3-C12cycloalkyl, optionally substituted C2-C12heteroseksualci, optionally substituted C6-C18aryl and optionally substituted C1-C18heteroaryl.

In one form of this variant implementation of R1arepresents N. In one form of this variant implementation of R1bthe present is the focus of a N. This provides compounds where R1formula:

.

In one embodiment, compounds of this invention R1cis an optional substituted With6-C18aryl. With6-C18the aryl may be a monocyclic, bicyclic or polycyclic part. In certain embodiments of the exercise With6-C18aryl represents monotypical part. In certain embodiments of the exercise With6-C18aryl represents a bicyclic part.

In one particular embodiment, R1cis an optional substituted With6-C18aryl selected from the group including optional substituted phenyl and optionally substituted naphthyl. Fragments can be unsubstituted or can be substituted by one or more optional substituents. A large number of optional substituents can be used, as defined above. Examples of particularly suitable optional substituents include, but are not limited to, F, Br, Cl, methyl, trifluoromethyl, ethyl, 2,2,2-triptorelin, isopropyl, propyl, 2-ethyl-propyl, 3,3-dimethyl-propyl, butyl, isobutyl, 3,3-dimethyl-butyl, 2-ethyl-butyl, pentyl, 2-methyl-pentyl, Penta-4-enyl, hexyl, heptyl, octyl, phenyl, NH2, cyano, phenoxy, hydroxy, met the XI, ethoxy, methylenedioxy, pyrrol-1-yl and 3,5-dimethyl-pyrazole-1-yl.

The substituents can be located in any substitutable position around aryl rings that are available for replacement, as will be clear to the person skilled in the art. Examples of suitable optional substituted phenyl compounds include, but are not limited to, 2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 2-trifluoromethyl-phenyl, 3-trifluoromethyl-phenyl 4-trifluoromethyl-phenyl 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-bromo-phenyl, 2-fluoro-phenyl 3-fluoro-phenyl, 4-fluoro-phenyl, 4-hydroxy-phenyl 4-phenyl-phenyl, 4-methyl-phenyl, 2,4-dichloro-phenyl, 3,4-dichloro-phenyl, 2,5-dichloro-phenyl, 2,6-debtor-phenyl, 2-chloro-6-fluoro-phenyl, 3-fluoro-4-chloro-phenyl, 3-methyl-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 3-chloro-4-methyl-phenyl, 2-hydroxy-phenyl 3-hydroxy-phenyl 4-hydroxy-phenyl, 4-ethoxy-phenyl, 3 phenoxy-phenyl, 4-phenoxy-phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 4-isopropyl-phenyl, 4-cyano-phenyl 3,4-dimethyl-phenyl, 2,4-dimethyl-phenyl, 4-tert-butyl-phenyl, 2,4-dimethoxy-phenyl and 3,4-methylenedioxy-phenyl.

Certain compounds of this invention include the following:

or their pharmaceutically acceptable salt or prodrug.

In order to help the reader, the names of the compounds suitable for use in this invention, as discussed above, are as follows:

(14) N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(3-guanidino the l)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(25) N-(((3S,5S)-3-(2-(diethylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime

(31) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime

(33) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(37) N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(38) N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(39) N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(49) N-(((3S,5S)-3-(2-amino-ethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(50) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)naphthalene-2-sulfonamide

(54) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(60) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo - N-methyl-2-naptime

(62) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-4-methyl-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo-2-naptime

(63) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(64) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(65) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-(isopropylamino)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(67) N-(((3S,5S)-1-(2,2-dif is retil)-3-(3-(3-methylguanine)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(71) (E)-N-(((3S,5S)-3-butyl-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide

(79) N-((S)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)ndimethylacetamide

(81) (S)-2-acetamido - N-((S)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)-3-(1H-imidazol-5-yl)propanamide

(83) propyl (S)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethylcarbamate

(85) N-((R)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)ndimethylacetamide

(86) (S)-2-acetamido-N-((R)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)-3-(1H-imidazol-4-yl)propanamide

(87) propyl (R)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethylcarbamate

(105) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(106) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)biphenyl-4-carboxamid

(107) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-1H-indole-2-carboxamide

(108) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)biphenyl-4-carboxamid

(109) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1H-indole-2-carboxamide

(110) N-(((3S,5S)-1-(2,2-diphenylether)3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-(naphthalene-2-yl)ndimethylacetamide

(111) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1,2,3,4-tetrahydronaphthalen-2-carboxamide

(112) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)quinoline-3-carboxamide

(113) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)cinoxacin-2-carboxamide

(114) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)isoquinoline-3-carboxamide

(115) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(116) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)quinoline-2-carboxamide

(117) N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(118) N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-(naphthalene-2-yl)ndimethylacetamide

(119) N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-1-naptime

(120) N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-(1H-indol-3-yl)ndimethylacetamide

(121) N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-(biphenyl-4-yl)ndimethylacetamide

(122) N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(123) N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-(naphthalene-2-yl)ndimethylacetamide

(124) N-(((3S,5S)-3-(4-aminobutyl)-1-(is aftalen-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-1-naptime

(125) N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-(naphthalene-1-yl)ndimethylacetamide

(126) N-(((3S,5S)-3-(4-aminobutyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(127) (S)- N-(((3S,5S)-3-(4-aminobutyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

(128) (R)-N-(((3S,5S)-3-(4-aminobutyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

(129) N-(((3S,5S)-3-(4-aminobutyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)benzofuran-2-carboxamide

(130) (R)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-(3-methylguanine)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

(131) (S)- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

(132) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzofuran-2-carboxamide

(133) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2,3-dihydro-1H-inden-2-carboxamide

(134) (R)- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

(135) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzo[b]thiophene-2-carboxamide

(136) of 2,4-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

p> (137) of 2,5-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(138) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(139) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)cyclohexanecarboxylic

(140) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-phenoxybenzamide

(141) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-4-phenoxybenzamide

(142) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1H-indole-2-carboxamide

(143) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-phenylpropanamide

(144) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dimethylbenzamide

(145) 4-tert-butyl-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(146) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2,4-dimethoxybenzamide

(147) 2-cyclohexyl-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)ndimethylacetamide

(148) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzo[d][1,3]dioxol-5-carboxamid

(149) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1H-benzo[d]imidazol-5-carboxamid

(150) N-(((3S,S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1H-benzo[d][1,2,3]triazole-5-carboxamide

(151) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)cyclopentanecarboxylic

(152) of 3,4-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(153) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)cinnamamide

(154) 3,5-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(155) 2-(2,4-dichlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)ndimethylacetamide

(156) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1-methoxy-2-naptime

(157) 2-(3,4-dichlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)ndimethylacetamide

(158) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-6-methoxy-2-naptime

(159) (E)-3-(2,4-dichlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(160) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-adamantane-1-carboxamide

(161) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-phenoxyacetamide

(162) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-methoxy-2-naptime

(163) 4-bromo-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(164) (S)-N-(((3S,5S-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-carboxamide

(165) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(166) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(thiophene-2-yl)acrylamide

(167) (R)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-carboxamide

(168) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-hydroxyphenyl)acrylamide

(169) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2-methoxyphenyl)acrylamide

(170) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-p-tolylacetate

(171) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2-(trifluoromethyl)phenyl)acrylamide

(172) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(3-forfinal)acrylamide

(173) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-methyl-3-phenylacrylate

(174) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-phenylcyclopropanecarboxylic

(175) 2-(2,4-dichlorophenoxy)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)ndimethylacetamide

(176) (E)-3-(3-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(177) N-(((3,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzo[d]thiazol-6-carboxamide

(178) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-5-phenylfuro-2-carboxamide

(179) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(3-methoxyphenyl)acrylamide

(180) 6-bromo-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(181) N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-phenethyl-1,4-diazepan-5-yl)methyl)-2-naptime

(182) N-(((3S,5S)-1-(3,4-dichlorophenacyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(183) N-(((3S,5S)-1-(2,4-dichlorophenacyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(184) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzo[b]thiophene-5-carboxamide

(185) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide

(186) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-methoxyphenyl)acrylamide

(187) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime

(188) (E)-3-(2-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(189) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2-hydroxyphenyl)acrylamide

(190) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-t-tailar lamed

(191) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(3-(trifluoromethyl)phenyl)acrylamide

(192) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(3-hydroxyphenyl)acrylamide

(193) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2-forfinal)acrylamide

(194) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-o-tolylacetate

(195) (Z)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-fluoro-3-phenylacrylate

(196) N-((1-(2,2-diphenylether)-2-oxo-3-(piperidine-4-yl)-1,4-diazepan-5-yl)methyl)-2-naptime

(197) N-((1-(2,2-diphenylether)-2-oxo-3-(piperidine-4-ylmethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(198) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide

(199) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-(trifluoromethyl)phenyl)acrylamide

(200) N-(((3S,5S)-1-(2,2-diphenylpropyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(201) N-(((3S,5S)-1-(cyclohexylmethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(202) N-(((3S,5S)-1-(1-adamantylamine)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(203) N-(((3S,5S)-1-((S)-1,1-diphenylpropane-2-yl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(204) N-(((3S,5S)-1((R)-1,1-diphenylpropane-2-yl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(205) N-(((3S,5S)-1-cyclohexyl-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(206) N-(((3S,5S)-1-((R)-1-fluoro-1,1-diphenylpropane-2-yl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(207) (E)-3-(2,6-differenl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(208) (E)-3-(2-chloro-6-forfinal)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(209) (E)-3-(4-bromophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(210) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-ethoxyphenyl)acrylamide

(211) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo-2-naptime

(212) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)cinnamamide

(213) (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide

(214) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1,4-dimethoxy-2-naptime

(215) N-(((3S,5S)-3-(3-(3,3-dimethylguanidine)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(216) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-6-hydroxy-2-naptime

(217) 6-amino-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(218) (E)-N-((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-p-tolylacetate

(219) (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide

(220) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime

(221) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-ethylhexanate

(222) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dimethylbenzamide

(223) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(224) N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-ethylhexanate

(225) N-(((3S,5S)-3-(3-(cyclohexylamino)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(226) N-(((3S,5S)-3-(3-guanidinopropionic)-1-(naphthalene-2-yl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(227) N-(((3S,5S)-1-((N-fluoren-9-yl)methyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(228) (E)-N-(((3S,5S)-3-(3-(cyclohexylamino)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide

(229) N-(((3S,5S)-1-(2,2-diphenylether)-3-(4-(isopropylamino)butyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(230) (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2,4-differenl)acrylamide

(231) (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-cyanophenyl)acrylamide

(232) (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenolate is)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(naphthalene-2-yl)acrylamide

(233) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-(4-pertenece)ndimethylacetamide

(234) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-5-(4-chlorophenyl)furan-2-carboxamide

(235) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-4-(1H-pyrrol-1-yl)benzamid

(236) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-oxo-1-phenylpyrrolidine-3-carboxamide

(237) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-5-(4-chlorophenyl)isoxazol-3-carboxamide

(238) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-5-(furan-2-yl)isoxazol-3-carboxamide

(239) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-phenylthiazol-4-carboxamid

(240) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-4-(3,5-dimethyl-1H-pyrazole-1-yl)benzamid

(241) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide

(242) N-(((3S,5S)-1-(2-cyclohexylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(243) N-(((3S,5S)-1-(2-(bicyclo[2.2.1]heptane-2-yl)ethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(244) N-(((3S,5S)-1-(2,2-bis(4-methoxyphenyl)ethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(245) N-(((3S,5S)-3-(3-(benzylamino)propyl)-1-(2,2-diphenyl what Tyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(246) N-(((3S,5S)-3-(3-(cyclopentylamine)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(247) N-(((3S,5S)-3-(3-(cyclobutylamine)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(248) N-(((3S,5S)-3-(3-(dicycloverine)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(249) N-(((3S,5S)-1-benzyl-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(250) N-(((3S,5S)-1-(2,2-bis(4-forfinal)ethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(251) N-(((3S,5S)-3-(3-guanidinopropionic)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(252) (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(5-methylthiophene-2-yl)acrylamide

(253) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-phenyl-1H-pyrazole-5-carboxamide

(254) (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)-N-methylacrylamide

(255) (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-4-methyl-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide

(256) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-yl)benzamid

(257) (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-bromophenyl)acrylamide

(258) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(pyrrolidin-1-yl)propyl)-1,4-diazepan-5-the l)methyl)acrylamide

(259) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)acrylamide

(260) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(261) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(pyrrolidin-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(262) N-(((3S,5S)-3-(3-(azetidin-1-yl)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(263) N-(((3S,5S)-3-(3-guanidinopropionic)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(264) N-(((3S,5S)-3-(3-guanidinopropionic)-1-(2-(naphthalene-2-yl)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(265) N-(((3S,5S)-1-((S)-2-acetamido-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(266) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)cinnamamide

(267) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-3,4-dimethylbenzamide

(268) 3,4-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)benzamide

(269) N-(((3S,5S)-1-((S)-2-(cyclobutanecarboxylic)-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(270) N-(((3S,5S)-1-((S)-2-(cyclohexanecarbonyl)-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(271) N-(((3S,5S)-3-(aminomethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(272) (E)-N-(((3S,5S)-3-(aminomethyl-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide

(273) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide

(274) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-p-tolylacetate

(275) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(276) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(277) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(278) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dimethylbenzamide

(279) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)cinnamamide

(280) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide

(281) 3,4-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(282) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3,4-dimethylbenzamide

(283) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)cinnamamide

(284) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide

(285) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-p-tolylacetate

(286) N-(((3S,5S)-1-(3,5-dimethylbenzyl)-3-(3-guanidinopropionic is)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(287) N-(((3S,5S)-1-((S)-2-benzamide-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(288) N-(((3S,5S)-1-((R)-2-benzamide-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(289) N-(((3S,5S)-3-(3-guanidinopropionic)-1-(2-methoxy-2-phenylethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(290) N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-(2-phenyl-2-propoxyethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(291) N-(((3S,5S)-1-(2-(benzyloxy)-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(292) N-(((3S,5S)-1-(2-(allyloxy)-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(293) (E)-N-(((3S,5S)-3-(3-acetamidophenyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-p-tolylacetate

(294) N-(3-((2S,7S)-4-(2,2-diphenylether)-3-oxo-7-(((E)-3-p-tolylacetate)methyl)-1,4-diazepan-2-yl)propyl)cyclohexanecarboxylic

(295) N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-(2-phenoxy-2-phenylethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(296) ethyl 3-((3S,5S)-5-((2-naptime)methyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-1-yl)-2-phenylpropanoate

(297) N-(((3S,5S)-1-(2-ethylbutyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(298) N-(((3S,5S)-1-((3,5-dimethylcyclohexyl)methyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(299) N-(2-((2S,7S)-7-(((E)-3-(4-chlorophenyl)acrylamide)methyl)-4-(2,2-diphenylether)-3-oxo-1,4-diazepan-2-yl)ethyl)cyclohexanecarboxylic

(300) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(2-cyclohexylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(301) N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-amino-ethyl)-1,4-diazepan-5-yl)ethyl)benzamide

(302) of 3,4-dichloro-N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-amino-ethyl)-1,4-diazepan-5-yl)ethyl)benzamide

(303) N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-amino-ethyl)-1,4-diazepan-5-yl)ethyl)-2-naptime

(304) N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)ethyl)benzamide

(305) 3,4-dichloro-N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)ethyl)benzamide

(306) N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)ethyl)-2-naptime

(307) N-(((3S,5S)-1-(3-(dimethylamino)-3-oxo-2-phenylpropyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(308) N-(((3S,5S)-3-(2-amino-ethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(309) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide

(310) of N-(((3S,5S)-1-(3-chloro-5-terbisil)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(311) N-(((3S,5S)-1-(3,5-diferensial)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(312) N-(((3S,5S)-3-(3-aminopropyl)-1-(3-chloro-5-terbisil)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(313) N-(((3S,5S)-3-(3-aminopropyl)-1-(3,5-diferensial)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(314) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(315) N-(((3S,5S)-3-(3-aminopropyl the l)-1-(2,6-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(316) N-(((3S,5S)-3-(3-aminopropyl)-1-(3,5-dimethoxybenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(317) N-(((3S,5S)-3-(3-aminopropyl)-1-(2-Chlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(318) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,3-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(319) N-(((3S,5S)-3-(3-aminopropyl)-1-(2,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(320) N-(((3S,5S)-3-(3-aminopropyl)-1-(3,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(321) N-(((3S,5S)-3-(3-aminopropyl)-1-(3-fluoro-5-methylbenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(322) N-(((3S,5S)-3-(3-aminopropyl)-1-(3-fluoro-5-(trifluoromethyl)benzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(323) N-(((3S,5S)-3-(3-aminopropyl)-1-(4-Chlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(324) N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(325) N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((1-phenylcyclohexyl)methyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(326) of 3,4-dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(327) N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(328) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(329) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(330) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-Ativ the Tyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide

(331) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(332) of 3,4-dichloro-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(333) N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(334) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-4-chloro-3-perbenzoic

(335) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-4-chloro-3-methylbenzamide

(336) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-chloro-4-perbenzoic

(337) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-chloro-4-methylbenzamide

(338) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(339) N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)ethyl)-2-naptime

(340) N-(((3S,5S)-3-(3-aminopropyl)-1-(3,5-bis(trifluoromethyl)benzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(341) N-(((3S,5S)-3-(3-aminopropyl)-1-(3-Chlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(342) N-(((3S,5S)-2-oxo-1-(2-phenylbutyl)-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(343) N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-(3-oxo-2-phenyl-3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(344) N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-(3-oxo-2-phenyl-3-(phenylamino)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(345) 3,4-dichloro-N-(2-((3S,5R)-1-(2,2-diphenylether)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)ethyl)benzamide

(346) of 3,4-dichloro-N-(2-((3S,5R)-3-(2-(diisopropylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)ethyl)benzamide

(347) N-(((3S,5S)-3-(aminomethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(348) N-(((3S,5S)-3-(aminomethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(349) (E)-N-(((3S,5S)-3-(aminomethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide

(350) of 3,4-dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)benzamide

(351) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(352) N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(353) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide

(354) of 3,4-dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(pyrrolidin-1-ylmethyl)-1,4-diazepan-5-yl)methyl)benzamide

(355) N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(pyrrolidin-1-ylmethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(356) N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((S)-2-phenylpropyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(357) N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((R)-2-phenylpropyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(358) N-(((3S,5S)-3-(2-(dimethylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan--yl)methyl)-2-naptime

(359) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime

(360) N-(((3S,5S)-3-(3-aminopropyl)-1-(3,5-diethylphenyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(361) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(diethylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(362) N-(((3S,5S)-3-(2-(diethylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(363) of 3,4-dichloro-N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(364) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(365) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(366) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(367) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(368) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(369) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime

(370) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(371) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo-2-naptime

(372) N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)6-fluoro-2-naptime

(373) 6-chloro-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(374) 6-bromo-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(375) N-(((3S,5S)-3-(2-amino-ethyl)-1-((3,5-dimethylcyclohexyl)methyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(376) N-(((3S,5S)-3-(2-amino-ethyl)-1-((3,5-dimethylcyclohexyl)methyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(377) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-((3,5-dimethylcyclohexyl)methyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide

(378) 6-chloro-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(379) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime

(380) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(381) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(382) N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(383) 3,4-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(384) N-(((3S,5S)-3-(3-aminopropyl)-1-((2,6-dimethylcyclohexyl)methyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(385) N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(386) 3,4-d is chloro-N-(((3S,5S)-1-((3,5-dimethylcyclohexyl)methyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(387) 3,4-dichloro-N-(((3S,5S)-1-((3,5-dimethylcyclohexyl)methyl)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(388) N-(((3S,5S)-3-(2-amino-ethyl)-1-(3-methyl-2-phenylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(389) N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(390) N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((R)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(391) 3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)propanamide

(392) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)propanamide

(393) N-(((2S,7S)-7-(((E)-3-(4-chlorophenyl)acrylamide)methyl)-4-(2,2-diphenylether)-3-oxo-1,4-diazepan-2-yl)methyl)picolinate

(394) N-(((3S,5S)-1-((R)-3-methyl-2-phenylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(395) N-(((3S,5S)-1-((S)-3-methyl-2-phenylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(396) (E)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-(4-isopropylphenyl)acrylamide

(397) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-isopropylphenyl)acrylamide

(398) (E)-3-(2,4-dimetilfenil)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(399) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2,4-dimetilfenil)acrylic Jerusalem.

(400) (E)-3-(2,4-differenl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(401) (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2,4-differenl)acrylamide

(402) of N-(((2S,7S)-7-(((E)-3-(4-chlorophenyl)acrylamide)methyl)-4-(2,2-diphenylether)-3-oxo-1,4-diazepan-2-yl)methyl)cyclohexanecarboxylic

(403) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-morpholinoethyl)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(404) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(2,5-dimethyl-1H-pyrrol-1-yl)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(405) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(2,5-dimethylpiperidin-1-yl)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide

(406) 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(407) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(408) (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)acrylamide

(409) 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(410) 3,4-dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(411) of 3,4-dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(412) benzyl ((3S,5S)-1-(2,2-is venilated)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methylcarbamate

(413) (E)-3-(4-bromophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

(414) 5-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)isoxazol-3-carboxamide

(415) 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(416) 3,4-dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)benzamide

(417) 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(418) of 3,4-dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)benzamide

(419) (E)-N-(2-((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)propan-2-yl)-3-(4-chlorophenyl)acrylamide

(420) (E)-3-(4-chlorophenyl)-N-(2-((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)propan-2-yl)acrylamide

(421) N-(((3S,5S)-3-(2-amino-ethyl)-1-((R)-2-(4-chlorophenyl)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(422) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-(4-chlorophenyl)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(423) N-(((3S,5S)-1-((R)-2-(4-chlorophenyl)propyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(424) N-(((3S,5S)-1-((S)-2-(4-chlorophenyl)propyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(425) 3,4-dichloro-N-(((3S,5S)-3-(2-(methyl(phenyl)amino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)shall ethyl)benzamide

(426) of 3,4-dichloro-N-(((3S,5S)-3-(2-(diethylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(427) 3,4-dichloro-N-(((3S,5S)-3-(2-morpholinoethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(428) of 3,4-dichloro-N-(((3S,5S)-2-oxo-3-(2-(phenylamino)ethyl)-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(429) N-(((3S,5S)-3-(2-(benzylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(430) N-(((3S,5S)-3-(2-(tert-butylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(431) of 3,4-dichloro-N-(((3S,5S)-3-(2-(4-methylpiperazin-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(432) N-(((3S,5S)-2-oxo-1-((R)-2-fenilpentil)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(433) N-(((3S,5S)-2-oxo-1-((S)-2-fenilpentil)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(434) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-4-(trifluoromethyl)benzamid

(435) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-4-(trifluoromethyl)benzamid

(436) N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-(trifluoromethyl)benzamid

(437) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(trifluoromethyl)benzamid

(438) 6-chloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(439) 3,4-dichloro-N-(((S,5S)-1-(3,5-dichlorobenzyl)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(440) 6-chloro-N-(((3S,5S)-3-(2-(isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(441) N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(442) N-(((3S,5S)-3-(2-(benzyl(methyl)amino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(443) 3,4-dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperazine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(444) of 3,4-dichloro - N-(((3S,5S)-3-(2-(methyl(pentyl)amino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(445) 3,4-dichloro-N-(((3S,5S)-3-(2-(diisopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(446) of 3,4-dichloro-N-(((3S,5S)-3-(2-(4-methylpiperidin-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(447) (S)-6-chloro-N-((2-oxo-1-(2-phenylbutyl)-3-(piperidine-4-yl)-1,4-diazepan-5-yl)methyl)-2-naptime

(448) (S)-6-chloro-N-(3-(1-isopenicillin-4-yl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(449) 3,4-dichloro-N-(((3S,5S)-3-(2-(3,5-dimethylpiperidin-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(450) of 3,4-dichloro-N-(((3S,5S)-3-(2-(4-hydroxypiperidine-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(451) 1-(2-((2S,7S)-7-((3,4-dichlorobenzamide)methyl)-3-oxo-4-((S)-2-phenylbutyl)-1,4-diazepan-2-yl)ethyl)piperidine-4-carboxylic acid

(452) N-(((3S,5S)-3-(2-(azepin-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-d is chlorobenzamide

(453) of 3,4-dichloro - N-(((3S,5S)-3-(2-((S)-2-methylpiperidin-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(454) N-(((3S,5S)-3-(2-(tert-butyl(methyl)amino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(455) 6-chloro-N-((3-(1-ethylpiperazin-4-yl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(456) (3S,5S)-5-((3,4-dichloraniline)methyl)-1-(2,2-diphenylether)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-2-he

(457) 6-chloro-N-(((3S,5S)-3-(2-guanidinate)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(458) 6-chloro-N-(((3S,5S)-3-(2-(3-methylguanine)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(459) N-(((3S,5S)-3-(2-amino-ethyl)-1-((R)-2-ethyl-3-methylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(460) N-(((3S,5S)-3-(2-amino-ethyl)-1-((S)-2-ethyl-3-methylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(461) of 3,4-dichloro-N-(((3S,5S)-1-((R)-2-ethyl-3-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(462) of 3,4-dichloro-N-(((3S,5S)-1-((S)-2-ethyl-3-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(463) N-(((3S,5S)-3-(2-amino-2-methylpropyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(464) N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(465) 3,4-dichloro-N-(((3S,5S)-3-(2-(isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(466) N-(((3S,5S)--(2-amino-ethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(467) 6-chloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(468) 6-chloro-N-(((3S,5S)-3-(2-methyl-2-(piperidine-1-yl)propyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(469) N-(((3S,5S)-3-(2-amino-ethyl)-1-((R)-2-ethyl-3-methylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(470) N-(((3S,5S)-3-(2-amino-ethyl)-1-((S)-2-ethyl-3-methylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(471) 6-chloro-N-(((3S,5S)-1-((R)-2-ethyl-3-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(472) 6-chloro-N-(((3S,5S)-1-((S)-2-ethyl-3-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(473) 6-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methylcarbamoyl)-2-natoinalist

(474) 6-chloro-N-(((3S,5S)-3-(2-(3-isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(475) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethyl-3-methylbut-3-enyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(476) 3,4-dichloro-N-(((3S,5S)-1-(2-ethyl-3-methylbut-3-enyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(477) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethyl-3-methylbut-3-enyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(478) 6-chloro-N-(((3S,5S)-1-((R)-2-ethyl-3-methylbut-3-enyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(479) 6-chloro-N-(((3S,5S)-1-((S)-2-ethyl-3-methylbut-3-enyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-d is azepin-5-yl)methyl)-2-naptime

(480) N-(((3S,5S)-1-(cyclohexylmethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)biphenyl-4-carboxamid

(481) N-(((3S,5S)-1-(cyclohexylmethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-(1H-indol-3-yl)ndimethylacetamide

(482) N-(((3S,5S)-1-(cyclohexylmethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)quinoline-3-carboxamide

(483) 3,4-dichloro-N-(((3S,5S)-3-(2-(4,4-deformability-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(484) 3,4-dichloro-N-(((3S,5S)-3-(2-(3,3-deformability-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(485) (3S,5S)-5-((3,4-dichloraniline)methyl)-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-2-he

(486) 3,4-dichloro-N-(((3S,5S)-1-(2-cyclopropylethyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(487) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-cyclopropylethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(488) 6-chloro-N-(((3S,5S)-1-(2-cyclopropylethyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(489) 3,4-dichloro-N-(((3S,5S)-3-(2-(2,5-dioxopiperidin-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(490) 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(3-ureidopropionic)-1,4-diazepan-5-yl)methyl)-2-naptime

(491) 3,4-dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(1,1,1-tryptophan-2-ylamino)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(492) 3,4-dichloro-N-(((3S,5S)-3-(2-(3,3-dimethyl-2,5-dioxopiperidin-1-yl)ethyl)-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide

(493) N-(((3S,5S)-3-(2-(azepin-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(494) 6-chloro-N-(((3S,5S)-3-(2-(3-isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(495) N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)biphenyl-4-carboxamid

(496) N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-phenylthiazol-4-carboxamid

(497) 4'-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)biphenyl-2-carboxamide

(498) 6-chloro-N-(((3S,5S)-3-(2-(N-isopropylacrylamide)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(499) 6-chloro-N-(((3S,5S)-3-((isopropylamino)methyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(500) 6-chloro-N-(((3S,5S)-3-(guanidinate)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(501) 2-(2,4-dichlorophenyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)ndimethylacetamide

(502) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(503) 3,4-dichloro-N-(((3S,5S)-1-(2,4-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(504) 3,4-dichloro-N-(((3S,5S)-1-(2,4-dichlorobenzyl)-3-(2-(methylsulfonyl)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(505) 3,4-dichloro-N-(((3S,5S)-1-(2,4-dichlorobenzyl)-3-(2-(4-methylphenylsulfonyl)ethyl)-2-oxo-1,4-Diaz is EN-5-yl)methyl)benzamide

(506) N-(((3S,5S)-3-(2-((S)-2-amino-3-methylbutanoyl)ethyl)-1-(2,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(507) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(508) 6-chloro-N-(((3S,5S)-1-(2,4-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(509) N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-(2-(thiophene-3-yl)butyl)-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(510) 6-chloro-N-(((3S,5S)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1-((R)-2-(thiophene-3-yl)butyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(511) 6-chloro-N-(((3S,5S)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1-((S)-2-(thiophene-3-yl)butyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(512) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethyl-2-methylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime

(513) 6-chloro-N-(((3S,5S)-1-(2-ethyl-2-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(514) 6-chloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-morpholinoethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(515) 6-chloro-N-(((3S,5S)-3-(2-morpholinoethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(516) 6-chloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(2-morpholinoethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

(517) 3,4-dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(2-morpholinoethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide

(518) N-(3,4-dichlorobenzyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)ndimethylacetamide

(519) 1-(4-Chlorobenzyl)-3-(((3S,5's)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)urea

(520) N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethyl-2-methylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide

(521) of 3,4-dichloro-N-(((3S,5S)-1-(2-ethyl-2-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(522) 6-chloro-N-(((3S,5S)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1-(2,3,5-trichlorobenzoyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(523) 6-chloro-N-(((3S,5S)-3-(2-(1-methylethylacetate)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(524) butyl 2-((2S,7S)-7-((6-chloro-2-naptime)methyl)-3-oxo-4-((S)-2-phenylbutyl)-1,4-diazepan-2-yl)ethylcarbamate

(525) (S)-6-chloro-N-((3-(1-isopropylpiperazine-4-yl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(526) 6-chloro-N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(527) 5-(4-chlorophenyl)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)isoxazol-3-carboxamide

(528) of 2,4-dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(529) N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-6-methoxy-2-naptime

(530) 6-chloro-N-(([a 513C,the 415N](3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)[13C]methyl)-2-naptime

(531) N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-1-methoxy-2-naptime

(532) (E)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-the l)ethyl)-1,4-diazepan-5-yl)methyl)-3-(4-(triptoreline)phenyl)acrylamide

(533) 5-(4-chlorophenyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)isoxazol-3-carboxamide

(534) of 2,4-dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide

(535) 5,6-dichloro-2-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)isoindoline-1,3-dione

(536) (E)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-(3-fluoro-4-(triptoreline)phenyl)acrylamide

(537) 6-methoxy-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(538) 1-methoxy-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

(539) (E)-3-(3-fluoro-4-(triptoreline)phenyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide, and

(540) 6-chloro-N-(([5,6,6-2H3](3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)[2H2]methyl)-2-naptime

or their pharmaceutically acceptable salt or prodrug.

Industrial utility

As indicated previously, the compounds of this invention are antagonists MC5R and, therefore, can be used to modulate the activity of MC5R or its fragment or analogue or functional equivalent by the fact that they are subjected MC5R or a fragment or analogue or functional the economic equivalent of the effects of the compounds of this invention.

Accordingly, the compounds of this invention can be used to treat any condition in which modulation of the activity of MC5R or its fragment or analogue or functional equivalent will result in a favorable impact on this state. As such, the compounds of this invention can be used in methods to treat, prevent or control status, or associated directly or indirectly with the activity of MC5R or its fragment or analogue or functional equivalent of a mammal, where the modulating MC5R amount of the compounds of this invention administered to a mammal. One condition associated with the activity of MC5R, represents the excess excretion of fat and status associated with it. In one embodiment, method condition selected from the group including acne, seborrhea and seborrheic dermatitis. In one embodiment, acne is chosen from the group comprising common acne, acne, nodular acne and lightning eels. In one particular embodiment, the condition is a common acne.

For example, decreasing regulation MC5R leads to a reduction in oil secretion and thus can be used in the treatment or prevention of a number of States in which the observed excess excretion of fat, namely acne, seborrhea and seborrheic d is rmatic.

The compounds of this invention can be also suitable for the treatment, prevention or control of a number of conditions that relate to biological processes, controlled MC5R, such as diseases associated with inflammation. The compounds may also be suitable for treating or preventing cancer, such as syndrome Muir-Torre or other cancerous tumors of the sebaceous glands.

Through its effect on the excretion of fat compounds of this invention may also find application in the treatment where it is desirable reduced excretion of fat, namely in cosmetic treatments. The compounds can thus be used in ways to reduce the oil secretion in a mammal, the method includes a stage on which to impose an effective amount of the compounds of formula (I).

Introduction compounds of formula (I) to a patient, such as people, can be done by topical application, by any of the conventional methods for enteral administration, such as oral or rectal, or by parenteral administration such as subcutaneous, intramuscular, intravenous and intradermal methods of application. The injection may be in the form of injection loading dose of a substance, or by continuous or intermittent infusion. Active connection, usually on the differences in a pharmaceutically acceptable carrier or diluent and in the quantity sufficient for delivery to the patient a therapeutically effective dose.

When applying the compounds of this invention can enter them in any form or method, which makes the compound bioavailable. The person skilled in the art of preparing formulations can readily select the proper form and method of administration, depending on the individual characteristics of the selected compound, of a condition that should be treated, the stage of the condition that should be treated, and other relevant circumstances. The authors refer to Remingtons Pharmaceutical Sciences, 19thedition, Mack Publishing Co. (1995) for more information.

The compounds of this invention can be entered separately or in the form of pharmaceutical compositions together with pharmaceutically acceptable carrier, diluent or excipient. The compounds of this invention, although effective in and of themselves, are usually developed and introduced in the form of their pharmaceutically acceptable salts, because these forms are usually more stable, easier to crystallize and have a high solubility.

However, the connection is usually used in the form of pharmaceutical compositions, which are prepared depending on the desired method of administration. As such, in an additional embodiment, the invention provides a pharmaceutical composition is, including the compound of Formula (I) and a pharmaceutically acceptable carrier, diluent or excipient. The compositions are prepared by methods well known in the prior art.

The compounds of formula (I) can be applied or enter together with one or more additional drug(s). The compounds of this invention can be used in conjunction with one or more other pharmaceutically-active compounds, such as other treatments for acne. In one embodiment, the other pharmaceutically active agent is chosen from the group comprising antibiotics, retinoids, anti-androgens and steroids. Examples of other pharmaceutically active compounds, which can be combined with the compound of the formula (I) and type in simultaneous or sequential combination thereof, may include, by non-limiting examples, other substances against acne, such as oral retinoids (such as isotretinoin), local retinoids (such as isotretinoin, adapalene, tazarotene), oral or topical antibiotics (such as clindamycin, erythromycin, minocycline, tetracycline, benzoyl peroxide) or hormonal therapy (e.g., drospirenone, norgestimate - ethinylestradiol, tsiproteronatsetat). As indicated, these components can be entered in a single composition or in separate compositions. With the introduction of the individual with whom tawah the compounds of this invention can be entered sequentially or simultaneously with other drug(s).

The compound of the present invention are typically combined with the carrier to obtain a dosage form suitable for the particular patient being treated, and the particular method of administration. For example, a composition intended for oral administration to humans may contain from about 0.5 mg to about 5 g of the compounds of this invention prepared with the appropriate and suitable amount of carrier which may vary from about 5 to about 99.95 percent of the total composition. Typical dosage forms will generally contain from about 1 mg to about 500 mg of the compounds of this invention, typically 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg of the compounds of this invention can also be for local delivery in the formulations, such as solutions, ointments, lotions, gels, creams, micro-emulsions or transdermal patches. For example, these local structures can contain from 0.005 to 5% (weight/weight or weight/volume) of compounds of this invention.

The pharmaceutical compositions of this invention for parenteral injection contain pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for conversion immediately before use in sterile inye the dummy solutions or dispersions. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or mediums include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), and suitable mixtures, vegetable oils (such as olive oil), and injectable organic esters, such as etiloleat. Proper fluidity can be maintained, for example, through the application of covering materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by applying a surface-active substances.

These compositions may also contain auxiliary agents such as preservatives, wetting agents, emulsifying agents and dispersing agents. Preventing exposure of microorganisms can be ensured by the inclusion of various antibacterial and antifungal substances, for example, paraben, chlorobutanol, fenolcarbonove acid and the like. May also be desired inclusion isotonic substances, such as sugars, sodium chloride and the like. Prolonged absorption of injectable pharmaceutical form can be called by the inclusion of substances which delay absorption such as aluminum monostearate and gelatin.

If necessary, and for more effective distribution, the compounds can be included in the honey is i.i.d. release or targeted delivery systems such as polymer matrices, liposomes, and microspheres.

Injectable formulations can be sterilized, for example by filtration through inhibiting bacteria filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersing in sterile water or other sterile injectable medium immediately before use.

Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms the active compound is mixed, with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or diluents, such as starches, lactose, sucrose, glucose, mannitol and silicic acid, B) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and gum Arabic, C) humectants such as glycerol, a) disintegrating agents such as calcium carbonate, potato or manioc starch, alginic acid, certain silicates and sodium carbonate, e) dissolution retarders, such as paraffin, f) absorption accelerators such as Quaternary ammonium compounds, g) moisturizing prophetic is Tami, such as, for example, cetyl alcohol and glycerylmonostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricating agents such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also contain buffer substances.

Solid compositions of a similar type can also be used as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar and high molecular weight polyethylene glycols and the like.

Solid dosage forms such as tablets, pills, capsules, pills and granules can be prepared with coatings and shells, such as intersolubility coating tablets and other coatings well known in the field of pharmaceutical preparation. They may optionally contain mud components, and may include a composition that they release only the active ingredient(s), or preferably in certain parts of the intestine, optional, extended way. Examples of coating compositions which can be used include polymeric substances and waxes.

When necessary and for more effective distribution, the compounds can be included in slowly wysw bodywise or targeted delivery systems such as polymer matrices, liposomes, and microspheres.

The active compounds can also be microencapsulating form, optionally with one or more of the above-mentioned fillers.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethylcarbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyleneglycol, dimethylformamide, oils (in particular, cottonseed oil, oil of groundnuts, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters sorbitan and mixtures thereof.

Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspendresume substances, sweetening, flavouring and otdushivayut substances.

Suspensions, in addition to the active compounds, may contain suspendresume substances, as in the example, ethoxylated isostearyl alcohols, polyoxyethylenated and sorbitane esters, microcrystalline cellulose, aluminum Metagalaxy, bentonite, agar-agar and tragakant and mixtures thereof.

Compositions for rectal or vaginal injection are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating fillers or carriers such as cocoa butter, polyethylene glycol or a suppository wax, which are solid at room temperature, but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound.

For topical application, the active substance may be in the form of ointment, cream, suspension, lotion, powder, solution, paste, gel, spray solution, aerosol or oil. Alternatively, the composition can be delivered via liposomes, nanosomes, ribosome or inside-diffuser environment. On the other hand, the composition can include a transdermal patch or a bandage, such as dressing, impregnated with the active ingredient and optionally one or more carriers or diluents. For administration in the form of a transdermal delivery system, the introduction of the dosage will, of course, more continuous and not intermittent in the course of the scheme p is AMA. Methods for manufacturing compositions for local application known in the art.

Compositions used for local applications usually contain a pharmaceutically acceptable carrier, which may be any medium that is available and pharmaceutically acceptable. Conventional pharmaceutically acceptable carriers that can be used in the compositions of this invention include water, ethanol, acetone, isopropyl alcohol, stearyl alcohol, freons, polyvinylpyrrolidone, propylene glycol, polyethylene glycol, fragrances, gel-producing materials, mineral oil, stearic acid, spermaceti, sorbitan, Monolit, Polysorbate, "twins", sorbitol, methylcellulose, percolator, mineral oil (liquid paraffin), which can represent any product is petroleum-based; modified or unmodified vegetable oils such as peanut oil, wheatgerm oil, Flaxseed oil, jojoba oil, oil of apricot pits, walnut oil, palm oil, pistachio oil, sesame oil, rapeseed oil, juniper oil, oil from corn germ, peach seed oil, poppy seed oil, pine oil, castor oil, oil from soybeans, safflower oil, coconut oil, hazelnut oil, oil from vinogradnyh seed, avocado oil, soybean oil, sweet almond oil, oil of calophylla, castor oil, olive oil, sunflower oil, or animal oils such as whale blubber, seal fat, menhatoy fat, liver fat halibut, cod liver oil, cod, tuna, turtle fat, fat horses ' hooves, goat legs, mink, otter, marmot and the like; synthetic oils such as silicone oil, such as dimethylpolysiloxane; alkyl and alkeneamine esters of fatty acids, such as isopropyl esters of myristic, palmitic and stearic acids and fatty difficult esters that are solid at room temperature; waxes such as lanolin wax, candelilla wax, spermaceti, cocoa butter, Shea butter, silicone waxes, hydrogenated oils which are solid at room temperature, the sugar-glycerides, oleates, myristate, linoleates, stearates, paraffin, beeswax, Carnauba wax, ozokerite, candelilla wax, microcrystalline wax; fatty alcohols, such as lauric, cetyl, ministerului, stearyl, palmately and alerby alcohols; polyoxyethylene fatty alcohols, and wax esters, lanolin and its derivatives, perhydrosqualene and saturated esters, Etisalat, isopropyl, al Kyl myristate, such as ESOP opererated, butylnitrite and deterministic, existiert, triglyceride esters, triglycerides of octanoic and decanoas acid, cetirizine, stearylamine (porcelanowe oil), fatty acids, polyhydric alcohols, polyester derivatives, fatty acid monoglycerides, polyethylene glycol, propylene glycol, alkylalkoxysilane, ammoniumnitrate, Soaps of fatty acids and hydrogenated polyisobutene and mixtures of waxes and oils.

Compositions for topical application can be in various forms. However, the composition can often take the form of an aqueous or oil solution or dispersion, or emulsion, or gel, or cream. The emulsion may be an emulsion of the type oil-in-water or emulsion of the type water-in-oil.

The oil phase of the emulsions of the type water-in-oil or oil-in-water may contain, for example: (a) hydrocarbon oils such as paraffin or mineral oil; (b) waxes, such as beeswax or paraffin wax; natural oils such as sunflower oil, oil of apricot pits, oil from the oil tree or jojoba oil; d) silicone oils such as Dimethicone, cyclomethicone or acidisation; (e) fatty acid esters, such as isopropyl, isopropylmyristate, dioctylmaleate, glyceridae and zetostearilovy; (f) fatty alcohols, such as t tilby alcohol or stearyl alcohol and their mixture (for example, clearily alcohol); (g) polypropylenglycol or polietilenglikolya esters, for example, PPG-14 butyl ether; or h) mixtures thereof.

Used emulsifiers can be any emulsifier known in the art for use in the emulsions of the type water-in-oil or oil-in-water. Known cosmetically acceptable emulsifiers include: (a) sesquioleate, such as servicesecurity available commercially, for example, under the trade name Arlacel 83 (ICI), or polyglyceryl-2-sesquioleate; (b) ethoxylated esters of derivatives of natural oils such as polyethoxysiloxane ester of hydrogenated castor oil, available commercially for example under the trade name Arlacel 989 (ICI); (C) silicone emulsifiers such as siliconpower available commercially, for example, under the trade name ABIL WS08 (Th. Goldschmidt AG); (d) anionic emulsifiers, such as Soaps of fatty acids such as stearate and potassium sulfates of fatty acids, for example, cetostearyl sodium, commercially available under the trade name Dehydag (Henkel); (e) ethoxylated fatty alcohols, for example the emulsifiers available commercially under the trade name Brij (ICI);] (f) esters sorbitan, for example the emulsifiers available commercially under the trade name Span (ICI); (g) ethoxylated esters sorbitan such as the R, the emulsifiers available commercially under the trade name Tween (ICI); (h) ethoxylated fatty acid esters, such as ethoxylated stearates, for example the emulsifiers available commercially under the trade name Myrj (ICI); (i) ethoxylated mono-, di - and triglycerides, for example the emulsifiers available commercially under the trade name Labrafil (Alfa Chem.); j) non-ionic self emulsifiable waxes, for example, wax, commercially available under the trade name Polawax (Croda); k) ethoxylated fatty acids, for example the emulsifiers available commercially under the trade name Tefose (Alfa Chem.); l) methylglucose esters, such as polyglyceryl-3 methylglucose distearate, available commercially under the name Tegocare 450 (Degussa Goldschmidt); or m) mixtures thereof.

Gels for local application can be aqueous or nonaqueous. Water gels are preferred. The gel will contain a thickener or gelatinous substance to impart sufficient viscosity to gel. A number of thickeners can be used in accordance with the nature of the liquid carrier and the desired viscosity, and they are listed below. Particularly suitable thickener is a copolymer acryloyldimethyltaurate acid (or its salt), preferably a copolymer of the monomer with another vinyl monomer. For example, the thickener is a copolymer salt acryloyldimethyl is owenboy acid with other vinyl monomer. Salt can be a salt of alkali metals of group I, but more preferably is an ammonium salt. Examples of suitable copolymer thickeners are: (i) ammonium acryloyldimethyltaurate I vinyl pyrrolidone copolymer, i.e. a copolymer of ammonium acryloyldimethyltaurate and vinylpyrrolidone (1-vinyl-2-pyrrolidone).

The composition may further include other active ingredients of skin care products, which are well known in the art, which can be effective to support the normal functioning of the skin. One group of preferred compositions include hydrolyzed milk protein to regulate sebum production.

The composition may further include other components that are well known to the specialist in the art, such as emollients, moisturizers, stabilizing emulsion, salt, preservatives, chelating substances or complexing compounds (connecting link), abrasives, antioxidants, stabilizers, pH regulators, surfactants, thickeners, diluents, flavors and dyes.

Compositions for topical application may preferably include a compound which enhances absorption or penetration of the active ingredient through the skin or other porazeny the zone. Examples of such amplifiers dermal penetration include dimethyl sulfoxide and related analogues.

The SYNTHESIS of COMPOUNDS of THIS INVENTION

General synthetic approach to the claimed products flows through the key intermediate product And produced as described in schemes 1 or 2.

Figure 1 amino acid-derived V-N(R2)-Y-CO2H (V=R1X or a protective group of the amine R1) is transformed into amide Weinrebe by activation of the carboxyl group and amidation of N-methylmethanamine. The addition of vinyl Grignard reagent produces aminoalkylindole, which is subjected to a paired connection with R6R7R8C-(CR5aR5b)rNH2aminoven component (shown as WNH2for the sake of simplicity). The resulting secondary amine acelerou under standard conditions of peptide compounds with protected amino acid, P2-NHCH(U)-CO2H, where U represents either end ZNR4aR4bside chain-protected final side chain, or a predecessor, which requires chemical modification for education final ZNR4aR4bthe side chain. Removing R2protective group follows the intramolecular by reductive amination of the ketone using standard conditions for the restoration, such as H2/Pd cat is the lyst NaBH4, NaBH3CN or NaBH(SLA)3with the formation of the key intermediate product A. If Y=CH2or CH2CH2then a is formed as the predominant diastereoisomer. If V=R1X and U=ZNR4aR4b, And is the final product.

Scheme 1: Synthesis of intermediate product And by intramolecular reductive amination

Figure 2 an alternative path to the desired intermediate product And begins with the same education amide Weinrebe, vinyl accession Grignard reagent and amine conjugated addition. At this stage, secondary amine protected by a protective group of the amine R4. The ketone is then recovery miniroot protected aminalonum ether, H2NCH(U)-CO2P5producing a mixture of diastereomers, which is conducted through the subsequent stages of the reaction. The ring system are then produced by removing the protective groups R4and R5, followed by the formation of amide bond using standard reagents peptide compounds. Alternative, R4the protective group is removed and receive a cyclization via thermal or base-induced cyclization with R5secure complex with ether. Cyclization produces a mixture of two diastereoisomers, a and b, of which preferably the second diastereoisomer And can be separated by chromatography.

Scheme 2: Synthesis of intermediate product And by intramolecular reductive amination

The key intermediate product And may represent the final product, if U=ZNR4aR4band V=R1X, but in other cases into the final product, as shown in schemes 3, 4 and 5.

In figure 3, where V=R1X, the final product is obtained by modifying U side chain, for example, removing the protective group P3or the removal of the protective group R3with subsequent chemical modification.

Scheme 3: V=R1X

In figure 4, where V=P1the final product is obtained by removal of the protective group R1with the subsequent introduction of the substituent R1X. If U=ZNR4aR4bthis produces the final product. Alternatively, the side chain of U then modify to obtain the final ZNR4aR4bgroup, as in figure 3.

In scheme 5, where V=R1the final product is obtained, first, by modifying the side chain of U to obtain the final ZNR4aR4bgroup as in scheme 3. This is followed by removal of the protective group R1with the subsequent introduction of the substituent R1X.

Figure 5: V=P1

Also is possible to modify the Deputy W, if necessary, during the sequence of these reactions.

Examples

The following examples are intended to show the disclosed embodiments of, and should not be construed as limiting. Additional connections other than those described below, can be obtained using the following schemes reactions, as mentioned above, or their respective variations or modifications. All source materials described in the Examples below, commercially available or easily synthesized by specialists in this field.

Equipment

Analysis of HPLC (high performance liquid chromatography) was performed on the cleaning system Agilent 1100 series with a Phenomenex Synergi 4µ Max-RP 80A, 50×2.00 mm analytical HPLC column, with detection of peaks by UV. In the standard analysis used a flow rate of 1 ml/min 0,05% triperoxonane acid (TFA) in water (solvent A) and 0.05% TFA in 90:10 acetonitrile:water (solvent B), using a gradient from 5% B (start) up to 95% b for 9 min Mass spectra were obtained on an Applied Biosystems MDS Sciex API 2000 LC/MS/MS triple quadrupole mass spectrometer and analyzed yourspouse mass spectrometry (ISMS). Preparative HPLC was performed on Waters Delta Prep 3000 HPLC system with detected peaks by UV (Waters model 486 custom absorption detector), using a Phenomenex Luna 10µC5 100A, 250×21,20 mm (20 mg scale), Phenomenex Luna 15µ C8(2) 100A, 250×30,00 mm (50 mg scale) or Phenomenex Luna 15µ C8(2) 100A, 250×50,00 mm (100 mg scale) HPLC column. When the solvent system used different gradients of 0.05% TFA in water (solvent A) and 0.05% TFA in 90:10 acetonitrile:water (solvent B).

The following examples 1-7 offer General methods of synthesis, which can be followed for carrying out the transformations described in schemes 1-5. For the formation of different end-products using these techniques, you need to change the variable group on the source material, or to change the variable group on one of the reagents depending on the nature of the reaction. The person skilled in the art it will be clear from reading the common methods how to change or source material, or the reagents used in the method for producing different end products. In addition, depending on the starting materials and reagents, you may need and/or desire to make a minor modification described in the General methods in order to provide the most easy synthesis of the required end product.

Example 1 - General methods - formation of amide Weinrebe

THIEF (benzotriazol-1-yl-oxy-Tris-(dimethylamino)-phosphodiester phosphate) reagent (100 mmol) and diisopropylethylamine (DIPEA) (100 mmol) are added to stir the th solution of amino acids (1) (100 mmol) in dichloromethane (DCM) (100 ml). The solution is then stirred at room temperature for 10 minutes, before adding the pre-mixed solution of N,O-dimethylhydroxylamine hydrochloride (100 mmol) and DIPEA (100 mmol) followed by stirring at room temperature overnight. DCM then removed by rotary evaporation, and the residue is absorbed in ethyl acetate (EtOAc) (200 ml). The organic phase is then washed with 1N HCl (3×100 ml), N2O (3×100 ml), saturated aqueous NaHCO3(3×100 ml) and with brine (1×10 ml). The organic phase is then dried (MgSO4) and EtOAc is removed to obtain the amide Weinrebe (2) in the form of white solids or oils.

Example 2 - General method - vinyl accession Grignard reagent for amide Weinreb for the formation of α,β-unsaturated ketones of the formula (3)

To Amida Weinrebe (2) (15 mmol) in DCM (10 ml) at 0°C. add vinylmania (45 mmol) in THF (45 ml). The reaction is stirred for 2 hours and checked by means of HPLC. The reaction is then cooled rapidly by adding thereto a mixture of ice and 1M HCl (200 ml). The aqueous mixture is extracted with DCM (3×100 ml) and the organic layers are combined and washed with 1M HCl (2×200 ml) and H2O (3×100 ml). The organic phase is dried (MgSO4to a solution of α,β-unsaturated ketone (3). α,β-unsaturated ketone (3) can be distinguished rotary evaporation and the and it can be used in solution without additional purification. If the goal is to use α,β-unsaturated ketone (3) in the solution, reduce the volume to 100 ml using rotary evaporation and stored for future use.

Example 3 General method - conjugate connection amine to α,β-unsaturated ketones of the formula (3) to obtain compounds of the formula (4)

To Amin W-NH2(7.4 mmol) in DCM (10 ml) add a solution of α,β-unsaturated ketone (3) (5.7 mmol) in DCM (50 ml). The solution was stirred at room temperature for 15 minutes or until until the analysis shows that all of the (3) spent. A solution of compound (4) is directly used without purification for the subsequent reaction.

Example 4 General method - acylation of aminoketone (4)

Amino acid P2-NHCH(U)-CO2H (15 mmol) and DIC (15 mmol) are added to a DCM solution containing 10 mmol of adduct 4 paired connection. The reaction was stirred at room temperature overnight. DCM is removed using rotary evaporation, and the residue is then subjected to column chromatography on silica gel, using white spirit:EtOAc to obtain 5.

Alternatively, DIC can be replaced by HATU (2-(7-Aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexaflurophosphate) (15 mmol) and DIPEA (15 mmol). The reaction is stirred at room temperature Sunoco. DCM is removed using rotary evaporation, and the residue is absorbed in EtOAc (100 ml). The organic layer was washed with saturated sodium bicarbonate solution (2×100 ml), a saturated solution of ammonium chloride (2×100 ml) and with brine (2×100 ml). The organic phase is dried, and the solvent is removed under reduced pressure. The residue is subjected to column chromatography on silica gel using petroleum ether:EtOAc to obtain 5.

Example 5 - General method - removing the protective groups R2and cyclization

The methodology selected for removal of the protective group P2, will vary depending on the specific nature of the protective group. As will be appreciated by the person skilled in the art, it is possible to use a larger number of potential protective groups, and the person skilled in the art will easily be able to determine a suitable method for removing any protective groups of the techniques known from the prior art. However, in order to help the reader, are common methods of removal of the most well-known protective groups.

R2=Fmoc: compound 5 (2 mmol) in DCM (3 ml) add diethylamine (20 mmol). The reaction was stirred at room temperature for 1 hour. DCM and diethylamin then removed using rotary evaporation. DCM (5 ml) and triacetoxyborohydride sodium (3 mmol) ZAT is added, and the reaction is stirred overnight at room temperature. The organic phase is washed with saturated sodium bicarbonate solution (25 ml), dried (MgSO4and remove DCM to obtain cyklinowanie product A. It can be cleaned using flash chromatography on silica gel or use without purification.

R2=Boc: compound 5 (2 mmol) in DCM (3 ml) is added TFA (3 ml) and the reaction stirred at room temperature for 2 hours. DCM and TFA then removed using rotary evaporation. Then add DCM (5 ml) and triacetoxyborohydride sodium (3 mmol) and the reaction stirred overnight at room temperature. The organic phase is washed with saturated sodium bicarbonate solution (25 ml), dried (MgS04) and remove the DCM to obtain cyklinowanie product A. It can be cleaned using flash chromatography on silica gel or use without purification.

R2=Cbz: a Mixture of crude 5 (1 mmol) and 5% Pd/C (200 mg) in 2-propanol (15 ml) is shaken at room temperature under hydrogen (30 psi (pounds per square inch)) within 24 hours. The mixture was then filtered through a pad of Celite and the filtrate concentrated under reduced pressure to obtain the crude product. To obtain And can be applied purified using flash chromatography on silica gel (100% EtOAc).

Example 6 - General method - removing the protective groups R1and aluchemie derivatives

The methodology selected for removal of the protective group P1, will vary depending on the specific nature of the protective group. As will be appreciated by the person skilled in the art, it is possible to apply a large number of possible protective groups, and the person skilled in the art will easily be able to determine a suitable method for removing any protective groups of the techniques known from the prior art. However, in order to help the reader, are common methods of removal of the most well-known protective groups.

Removing the protective groups, R1=Cbz:

To cyklinowanie product (1 mmol) in methanol (5 ml) is added a catalytic Pd/C. the Reaction is stirred in an atmosphere of hydrogen overnight. The reaction mixture was filtered through Celite and the methanol removed with rotary evaporation to obtain the free amine. The amine can be used in subsequent reactions without purification.

Removing the protective groups, R1=Boc:

To cyklinowanie product (1 mmol) in DCM (1 ml) is added TFA (1 ml) and the reaction stirred at room temperature for 2 hours. The solvent is removed via rotary evaporation to obtain the amine TFA salt, which can be used in subsequent reactions without purification.

Removing the protective groups, R1=Alloc:

To cyklinowanie products is a (1 mmol) in DCM (6 ml) is added 1,3-dimethylbarbituric acid (0.2 mmol) and palladium tetranitroaniline (10 mg). The reaction of the vacuum and stirred at room temperature for 1 hour. DCM removed under reduced pressure to obtain the crude free amine, which can be used in subsequent reactions without purification.

Obtaining derivatives with R1X, when X=S(=O):

To the free amine (1 mmol) in DCM (5 ml) is added DIPEA (1 mmol), THIEF reagent (1.5 mmol) and the acid component R1CO2H (1.5 mmol). The reaction was stirred at room temperature for 2 hours. Rotary evaporation and preparative HPLC gives purified adduct.

Example 7 - General method - modification of U by removing the protective groups R3and dialkylamino the dibromide

The methodology selected for the inoculation of U by removing the protective groups and obtain derivatives will vary depending on the specific nature of the group U. As will be appreciated by the person skilled in the art, possibly a large number of modifications, and the person skilled in the art will easily be able to determine a suitable method for turning in the desired R group. However, in order to help the reader, is one common method of inoculation, usually used for the following examples.

R3=Boc:

The protected amine (1 mmol) in DCM (5 ml) is added TFA (5 ml) and the reaction lane is mesilat at room temperature for 2 hours. DCM (20 ml) is added and the solution washed with saturated sodium bicarbonate solution (20 ml), dried (MgSO4) and evaporated to obtain the crude amine. To the crude amine added DMF (dimethylformamide) (0.5 ml), potassium carbonate (50 mg) and 1,5-dibromethane (5 mmol). The reaction mixture was stirred at room temperature for 1.5 hours, then add DCM (20 ml), the organic layer was washed with saturated sodium bicarbonate solution (20 ml) and H2O (20 ml), dried (MgSO4) and evaporated. The residue can be cleaned preparative HPLC to obtain piperidinium product. The purified product is isolated in the form of the TFA salt, but easily converted into the free base by neutralization with aqueous NaHCO3and extraction into an organic solvent, or optionally converted into the HCl salt by acidification of 1N HCl.

Example 8 - Synthesis of compound 8 N-(2-(methoxy(methyl)amino)-2-oxoethyl)-2-naphthalide

To a mixture of 2-naphthoic acid (5.8 g, or 33.7 mmol), 2-amino-N-methoxy-N-methylacetamide (Gly amide Weinreb; prepared from Boc-Gly amide Weinrebe 15, as in the Example 44) (3.8 g, 32.1 mmol) and DIPEA (12.0 ml, for 68.9 mmol) in DCM (70 ml) was added a THIEF (14.9 g, or 33.7 mmol) in one portion at room temperature. The resulting mixture was stirred for 1 hour, then added a saturated aqueous solution of NaHCO3. the content of inorganic fillers layer was washed with brine (5×60 ml) and 1 N HCl (2×30 ml), dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product, which was used in subsequent reactions without further purification.

Example 9 - Synthesis of compound (9) N-(2-(methoxy(methyl)amino)-2-oxoethyl)-2-naphthalide

To a solution of 8 (3.5 g, is 12.85 mmol) in dry THF (10 ml) was slowly added a solution of vinylmania in THF (1 M, 31 ml) at 0°C. After addition the mixture was stirred at room temperature for 1 hour, then poured into ice-cold solution of 1 N HCl (50 ml). The aqueous layer was extracted with DCM (3×80 ml) and the combined organic layers were dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product. MS (ESI) 240 (M+1); HPLC tR5,46 minutes.

Example 10 Synthesis of compound 10 N-(4-(3,5-dichloraniline)-2-oxobutyl)-2-naphthalide

To a solution of 3,5-dichloraniline (12 mg, 0,068 mmol) in DCM (0.2 ml) was added a solution of 9 (13 mg, 0,054 mmol) in DCM (0.5 ml) at room temperature. The resulting mixture was stirred until then, until all of the 9 did not trashdolls (within one hour) and then used directly in subsequent reactions. MS (ESI) 415 (M+1); HPLC tR6.00 minutes.

Example 11 Synthesis of compound (11) (8)-N-(4-(5-(3-Pbf-guanidino)-2-(Fmoc-amino)-N-(3,5-dichlorobenzyl)pentane is IDO)-2-oxobutyl)-2-naphthalide

To a solution of freshly prepared aminoketone 10 in DCM (2 ml) was added Fmoc-L-Arg(Pbf)-OH (53 mg, 0,082 mmol), followed by addition of DIC (12,5 µl, 0,082 mmol) at room temperature. The resulting mixture was stirred for 2 hours, then the solvent was removed under reduced pressure. The residue was filtered through a short plug of silica gel, elwira DCM followed EtOAc to obtain the desired product 11 in the form of a white solid. It was used in the next step without additional purification. MS (ESI) 1045 (M+1); HPLC tR9.99 minutes.

Example 12 - Synthesis of compound 12 (S)-N-(4-(5-(3-Pbf-guanidino)-2-amino-N-(3,5-dichlorobenzyl)pentanolide)-2-oxobutyl)-2-naphthalide

Diethylamine (0.5 ml) was added to Frnoc-protected 11 (56 mg, 0,054 mmol) at room temperature and the resulting mixture was stirred for 30 minutes. Excessive diethylamine removed under reduced pressure to obtain the desired free amine 12. It was used in the next step without additional purification. MS (ESI) 823 (M+1); HPLC tR7,49 minutes.

Example 13 Synthesis of compound 13 N-(((3S,5S)-3-(3-(3-Pbf-guanidino)propyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naphthalide

Aminoketone 12 (44 mg, 0,053 mmol) in DCM (2 ml) was collisionally by adding NaBH(SLA)3 (40 mg, 0.18 mmol) in one portion at room temperature. The resulting mixture was stirred for 3 hours followed by the addition of saturated aqueous NaHCO3(3 ml). The aqueous layer was extracted with DCM (3×3 ml)and the combined organic layers were dried over MgSO4that was filtered and concentrated under reduced pressure. The residue was filtered through a short plug of silica gel, elwira DCM followed EtOAc, then EtOAc/IPA (9:1)to obtain the target product 13 in the form of a white solid. It was used in the next step without additional purification. MS (ESI) 807 (M+1); HPLC tR7.75 minutes.

Example 14 Synthesis of compound 14 N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naphthalide

A solution of TFA/DCM (2:1) (1 ml) with 5% H2O added 13 at room temperature and the resulting mixture was stirred for 4 hours. The solvents were removed under reduced pressure and the residue was purified using preparative HPLC (100% H2O to acetonitrile/N2About 9:1, gradient) to obtain 14 (7,6 mg) in the form of a white solid (TFA salt). The total yield of (9) was approximately 18%. MS (ESI) 556,2 (M+1); HPLC tR5,74 minutes.

Example 15 Synthesis of compound 15 tert-butyl 2-(methoxy(methyl)amino)-2-oxoethylidene (Boc-Gly amide Weinreb)

To a stirred mixture of Boc-Gly-OH (20 g, 114,1 mmol), DIPEA (to 19.8 ml, 114,1 mmol) and the THIEF (50.5 g, 114,1 mmol) in DCM (20 ml) was added a pre-mixed solution of N,O-dimethylhydroxylamine (11.2 g, 114,1 mmol) and DIPEA (to 19.8 ml, 114,1 mmol) in DCM (20 ml) at room temperature. The resulting mixture was stirred for 16 hours, then washed 1N HCl (3×120 ml), H2O (3×120 ml), saturated aqueous NaHCO3(3×120 ml) and with brine (40 ml), dried over MgSO4that was filtered and concentrated under reduced pressure to obtain 15 in the form of a white solid (20 g, 80%)which was used in the next step without additional purification. MS(ESI) 219 (M+1); HPLC tR4,12 minutes.

Example 16 Synthesis of compound 16 tert-butyl 2-exabot-3-talkabout

At 0°C solution of vinylmania in THF (184 ml, 1 M) was added in one portion to the amide Weinrebe 15 (20 g, of 91.6 mmol) under nitrogen with stirring. The resulting mixture was allowed to mix for 2 hours and poured into a mixture of 1N HCl/ice (400 ml). The aqueous mixture was extracted with DCM (5×100 ml), the combined DCM extract was washed 1N HCl (2×100 ml), saturated aqueous NaHCO3(100 ml) and with brine (100 ml), then dried over MgSO4. The solvent was removed under reduced pressure, the obtained ketone 16 (12.9 g, 76%) in the form of a pale yellow oil, which was used in the next the stage without additional purification. MS(ESI) 186 (M+1); HPLC tR4,19 minutes.

Example 17 Synthesis of compound 17 tert-butyl 4-(2,2-diphenylethylamine)-2-oxobutyrate

To a stirred solution of 2,2-diphenylethylamine (0.33 g, of 1.66 mmol) in DCM (10 ml) was added α,β-unsaturated ketone 16 (0.31 g, of 1.66 mmol) at room temperature. Stirring was continued for 2 hours, the crude reaction mixture 17 was used in the next step without purification. MS(ESI) 383 (M+1); HPLC tR5,98 minutes

Example 18 Synthesis of compound 18 (S)-tert-butyl 3-methyl-4,8-dioxo-10-phenyl-2,9-dioxa-3,7-dosagecan-6-carboxylate

To a suspension of the salt of Cbz-L-Asp-OtBu-DCHA (10.1 g, 20.0 mmol), N,O-dimethylhydroxylamine-HCl (5.9 g, of 60.5 mmol) and DIPEA (12.0 ml, for 68.9 mmol) in DCM (150 ml) was added a THIEF (10.6 g, 24,0 mmol) in one portion at room temperature. The resulting suspension was stirred for 3 hours, then added H2O (100 ml). The organic layer was washed in 1 N HCl (2×100 ml), saturated aqueous NaHCO3(2×100 ml) and with brine (3×100 ml) and then dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product. Purification using flash chromatography on silica gel (Petefi/ EtOAc 1:2) gave 18 (6.4 g, 87%) in the form of a colorless oil. MS (ESI) 367 (M+1); HPLC tR6.87 in minutes.

Example 19 Synthesis of compound 19 (S)-3-methyl-4,8-di the CSR-10-phenyl-2,9-dioxa-3,7-dosagecan-6-carboxylic acid

Compound 18 (300 mg, 0.82 mmol) was dissolved in TFA/DCM (1:1) solution (2 ml) and the resulting mixture was stirred at room temperature for 2 hours. The solvents were removed under reduced pressure, and the residue re-dissolved in DCM (10 ml). This solution was washed in 1 N HCl (1×10 ml) and the organic layer was dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product 19 (235 mg, 92%)which was used in subsequent reactions without further purification. IMS (ESI) 311 (M+1); HPLC tR4,96 minutes.

Example 20 Synthesis of compound 20 (S)-benzyl 8-(2,2-diphenylether)-3,16,16-trimethyl-4,7,11,14-tetraoxo-2,15-dioxo-3,8,13-triazapentadiene-6-ylcarbamate

Compound 20 was obtained from compound 17 and 19, following the method of Example 4. MS (ESI) 675 (M+1); HPLC tR8,31 minutes.

Example 21 Synthesis of compound 21 tert-butyl ((3S,5S)-1-(2,2-diphenylether)-3-(2-(methoxy(methyl)amino)-2-oxoethyl)-2-oxo-1,4-diazepan-5-yl)methylcarbamate

A mixture of crude 20 (350 mg) and 5% Pd/C (200 mg) in 2-propanol (15 ml) which was at room temperature under hydrogen (30 psi) for 24 hours. The mixture then was filtered through a pad of Celite and the filtrate was concentrated under reduced pressure to obtain the crude product. Purification using flash x is matography on silica gel (100% of EtOAc) gave 21 (175 mg, 65% after 3 stages) in the form of a white solid. MS (ESI) 525 (M+1); HPLC tR6,24 minutes.

Example 22 Synthesis of compound 22 2-((2S,7S)-7-(aminomethyl)-4-(2,2-diphenylether)-3-oxo-1,4-diazepan-2-yl)-N-methoxy-N-methylacetamide

Compound 21 (175 mg, of 0.333 mmol) was dissolved in TFA/DCM (1:1) solution (1 ml) and the resulting mixture was stirred at room temperature for 2 hours. The solvents were removed under reduced pressure and the residue re-dissolved in EtOAc (20 ml). A saturated aqueous solution of NaHCO3(10 ml) and brine (10 ml) was added to the above solution, and the aqueous layer was extracted with EtOAc (9×20 ml). The combined organic layers were dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product 22 (120 mg, 85%) in the form of a yellow solid, which was used in subsequent reactions without further purification. MS (ESI) 425 (M+1); HPLC tR5,20 minutes.

Example 23 Synthesis of compound 23 N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-(methoxy(methyl)amino)-2-oxoethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naphthalide

To a solution of 22 (50 mg, 0.118 the mmol) and 6-fluoro-2-naphthoic acid (27 mg, 0,142 mmol) in DCM (4 ml) was added DIC (22 μl, 0,142 mmol) at room temperature. The resulting mixture was stirred for 2 hours, then the solvent was removed when eigendom pressure to obtain the crude product. Purification using flash chromatography on silica gel (elwira petroleum ether:EtOAc (1:1), then EtOAc) gave 23 (29 mg, 41%) in the form of a white solid. MS (ESI) 597 (M+1); HPLC tR6.75 minutes.

Example 24 Synthesis of compound 24 N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-oxoethyl)-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naphthalide

To a solution of 23 (29 mg, 0,049 mmol) in dry THF (1 ml) was added LiAlH(OtBu)3(38 mg, 0,145 mmol) in one portion at room temperature and the resulting suspension was stirred overnight. This slurry is then slowly poured into a cold (0°C) 0.4 M aqueous solution of KHSO4(2 ml, 0.8 mmol) and the resulting mixture was diluted in EtOAc (3 ml). The aqueous layer was extracted with EtOAc (3×3 ml) and the combined organic layers were washed 1 N HCl (3×6 ml), saturated aqueous NaHCO3(1×6 ml) and with brine (1×6 ml). The organic solution is then dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product 24 (24 mg, 91%)which was used in subsequent reactions without further purification. MS (ESI) 538 (M+1); HPLC tR6,41 minutes.

Example 25 Synthesis of compound 25 N-(((3S,5S)-3-(2-(diethylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naphthalide

To a solution of 24 (24 mg, 0,044 mmol) in DCM (2 ml) was added diethylamine (55 μl, 0,532 mmol) in to the room temperature. After stirring for 5 minutes to the above solution was added NaBH(SLA)3(20 mg, 0,090 mmol) in one portion and the resulting suspension was stirred for another 10 minutes To the suspension was added a saturated aqueous solution of NaHCO3(4 ml) and the aqueous layer was extracted with DCM (3×4 ml). The combined organic layers were washed with brine (10 ml), dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product. This crude product was purified using preparative HPLC (100% H2O to 90:10 acetonitrile:H2O, gradient) to obtain 25 in the form of a white solid (TFA salt). MS (ESI) 595,3 (M+1); HPLC tR6.22 minutes.

Example 26 Synthesis of compound 26 benzyl 2-(methoxy(methyl)amino)-2-oxoethylidene

To Cbz-glycine (10 g, of 47.8 mmol, Aldrich) in DCM (100 ml) was added a THIEF reagent (21,5 g, to 48.6 mmol) and DIPEA (6.5 ml, 46,0 mmol). After stirring at room temperature for 10 min was added N,O-dimethylhydroxylamine (4.9 g, a 50.2 mmol) and DIPEA (6.5 ml, 46,0 mmol). The reaction was stirred at room temperature overnight. DCM was removed via rotary evaporation and the residue is absorbed in EtOAc (100 ml). The organic phase is washed H2O (3×100 ml), saturated sodium bicarbonate solution (3×100 ml), H2O (3×100 ml), 1M hydrochloric acid (3×100 ml), hydrochloric R is the target (3×100 ml). The organic phase was dried (MgSO4and removed EtOAc to obtain the amide Weinrebe 26 in the form of white solids (7.78 g, 64%).

Example 27 Synthesis of compound 27 benzyl 2-exabot-3-talkabout

To Amida Weinrebe 26 (to 3.89 g, 15,42 mmol) in DCM (10 ml) at 0°C was added vinylmania (45 mmol) in THF (45 ml). The reaction was stirred for 2 hours and monitoring using HPLC. The reaction was added to a mixture of ice and 1M hydrochloric acid (200 ml). The aqueous mixture was extracted with DCM (3×100 ml) and washed 1M hydrochloric acid (2×200 ml) and H2O (3×100 ml). The organic phase was dried (MgSO4and the volume was reduced to 100 ml using rotary evaporation. α,β-unsaturated ketone 27 kept and used in solution without purification.

Example 28 Synthesis of compound 28 (S)-9-fluorenylmethyl 10-(2,2-diphenylether)-2,2-dimethyl-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-trasaction-8-ylcarbamate

2,2-diphenylethylamine (0.95 g, 7.4 mmol) in DCM (10 ml) was added α,β-unsaturated ketone 27 (5.7 mmol) in DCM (75 ml). After stirring at room temperature for 15 minutes was added Fmoc-L-2,4-diaminobutane acid(Vos)-(2.4 g, 8,55 mmol) and DIC (of 0.87 ml, 5.6 mmol). The reaction was stirred at room temperature overnight. DCM was removed via rotary evaporation and the residue was subjected to column chromatography on silica gel the use of petroleum ether:EtOAc (1:1 to 0:1) to obtain 28 (1.5 g, 31%).

Alternatively, 2,2-diphenylethylamine (0.97 g, 7.4 mmol) in DCM (20 ml) was added α,β-unsaturated ketone 27 (5,95 mmol) in DCM (40 ml). After stirring at room temperature for 15 minutes was added Fmoc-L-2,4-diaminobutane acid(Vos)-(2.4 g, 8,55 mmol), DIPEA (2.5 ml) and HATU (2.3 g, 6.0 mmol). The reaction was stirred at room temperature overnight. DCM was removed using rotary evaporation, and the residue is absorbed in EtOAc (100 ml). The organic layer was washed with saturated sodium bicarbonate solution (2×100 ml), a saturated solution of ammonium chloride (2×100 ml) and with brine (2×100 ml). The organic phase is dried, and the solvent was removed under reduced pressure. The residue was subjected to column chromatography on silica gel using petroleum ether:EtOAc (3:1 to 1:1 to 0:1) to obtain 28 (0,86 g, 17%).

Example 29 Synthesis of compound 29 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-(benzyloxycarbonylamino)-1-(2,2-diphenylether)-1,4-diazepan-2-it

To Compound 28 (1.5 g, 1.8 mmol) in DCM (3 ml) was added diethylamine (1.5 ml, 14.5 mmol). The reaction was stirred at room temperature for 1 hour. DCM and diethylamin removed using rotary evaporation. Added DCM (5 ml), triacetoxyborohydride sodium (0.4 g, 1.9 mmol)and the reaction was stirred overnight at room temperature. The organic phase is washed with saturated Rast is or sodium bicarbonate (25 ml), dried (MgSO4) and DCM was removed to obtain cyklinowanie product 29, which was used in the next step without purification.

Example 30 Synthesis of compound 30 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-aminomethyl-1-(2,2-diphenylether)-1,4-diazepan-2-it

To cyklinowanie product 29 in methanol (5 ml) was added catalytic Pd/C. the Reaction was stirred under atmosphere of hydrogen overnight. The reaction mixture was filtered through Celite and the methanol was removed via rotary evaporation to obtain the amine 30 (0.7 g, 83% from 28).

Example 31 Synthesis of compound 31 N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naphthalide

To the amine 30 (0.08 g, 0,17 mmol) in DCM (1 ml) was added DIPEA (0.25 ml), THIEF reagent (0.08 g, 0.18 mmol) and 6-fluoro-2-naphthoic acid (0.06 g, 0.32 mmol). The reaction was stirred at room temperature for 2 hours. TFA (1 ml) was added and the reaction was stirred at room temperature for 2 hours. Rotary evaporation and preparative HPLC received 31 (0.05 g, 54%). IMS (ESI) to 539.3 (M+1); HPLC tRmin of 5.92

Example 32 Synthesis of compound 32 6-chloro-2-naphthoic acid

A suspension of 6-bromo-2-naphthoic acid (3.0 g, 11,47 mmol), CuCl (11,7 g, 114,64 mmol) and CuI (2,19 g, 11,50 mmol) in degassed DMF (45 ml) was heated to boiling under argon is in the dark for 4 hours. After cooling to room temperature the solution decantation in water (H2O (200 ml) and the resulting mixture was extracted with EtOAc (2×500 ml). Then the combined organic layers were washed H2O (4×500 ml), then with brine (1×500 ml), dried over MgSO4that was filtered and concentrated under reduced pressure until dry. The residue was ground into powder with CH2CN and the resulting solid is then recrystallize from EtOAc to obtain the pure product 32 (2.2 g, 93%) in the form of an off-white solid. HPLC tR6,47 minutes

Example 33 Synthesis of compound 33 (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide

To the amine(E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-amino-ethyl)-1,4-diazepan-5-yl)methyl)acrylamide (21 mg, 0.05 mmol) in DMF (0.25 ml) was added K2CO3(5 mg) and 1,5-dibromethane (of 0.066 ml, 0.5 mmol). The reaction mixture is left at room temperature for 4 hours. The solvent was removed under high vacuum, and the residue was purified using pre-HPLC to obtain 8 mg (~30%) of 33 as a TFA salt. MS (ESI) 599,4 (M+1); HPLC tRmin of 6.31

Example 34 Synthesis of compound 34 (S)-9-fluorenylmethyl 10-(2-phenylbutyl)-2,2-dimethyl-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-trasaction-bicarbonate

2-phenylbutyraldehyde (0.26 g, 1.4 mmol) in DCM (10 ml) and DIPEA (0.25 ml, 1.8 mmol) was added α,β-unsaturated ketone 27 (1.06 mmol) in DCM (20 ml). After stirring at room temperature for 15 min was added Fmoc-diaminobutane acid(Vos)-(0.7 g, 1.56 mmol) and DIC (0.25 ml, of 1.61 mmol). The reaction was stirred at room temperature overnight. DCM was removed using rotary evaporation, and the residue was subjected to column chromatography on silica gel using petroleum ether:EtOAc (1:1-0:1), affording Compound 34 as a mixture of diastereomers (0.17 g, 21%).

Example 35 Synthesis of compound 35 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-(benzyloxycarbonylamino)-1-(2-phenylbutyl)-1,4-diazepan-2-it

To Compound 34 (0.17 g, 0.2 mmol) in DCM (3 ml) was added diethylamine (1.5 ml). The reaction was stirred at room temperature for 1 hour. DCM and diethylamin removed using rotary evaporation. DCM (5 ml) and triacetoxyborohydride sodium (0.1 g, 0.47 mmol) was added and the reaction was stirred overnight at room temperature. The organic phase is washed with saturated sodium bicarbonate solution (25 ml), dried (MgSO4) and DCM was removed to obtain cyklinowanie product 35 as a mixture of diastereoisomers (0.11 g, 100%).

Example 36 Synthesis of compound 36 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-(aminomethyl)-1-(2-phenylbutyl)-14-diazepan-2-it

To cyklinowanie product 35 (0.11 g) in methanol (5 ml) was added catalytic Pd/C. the Reaction was stirred under atmosphere of hydrogen overnight. The reaction mixture was filtered through Celite and the methanol was removed via rotary evaporation to obtain the amine 36 as a mixture of diastereoisomers (0.11 g, 100%).

Example 37 Synthesis of compound 37 (3S,5S)-3-(2-amino-ethyl)-5-(N-2-naftopidil)-1-(2-phenylbutyl)-1,4-diazepan-2-it

To the amine 36 (0.02 mg, 0.05 mmol) in DCM (1 ml) was added DIPEA (0.1 ml, 0.7 mmol), THIEF reagent (0.02 mg, 0.045 mmol) and 2-naphthoic acid (0.015 mg, 0.09 mmol). The reaction was stirred at room temperature for 2 hours. Added TFA (1 ml) and the reaction was stirred at room temperature for 2 hours. Rotary evaporation and preparative HPLC received 37 as a mixture of diastereomers (13,4 mg, 57%). MS (ESI) 473,4 (M+1); HPLC tR5,59 minutes

Example 38 Synthesis of compounds 38-39 N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naphthalide and N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naphthalide

Prepared from Compound 37 by alkylation as in Example 33. Preparative HPLC purification of separated two diastereoisomer. Proper configuration set the re-synthesis of compounds with (S)-2-phenylethylamine 43 or (R)-2-phenylethylamine. 38: MS (ESI) to 541.3 (M+1); HPLC tR5,78 min; 39: MS (ESI) to 541.3 (M+1); HPLC tR5,67 minutes

Example 39 Synthesis of compound 40 (S)-2-phenylbutane

To a suspension of sodium borohydride (2,36 g of 62.4 mmol) in THF (50 ml) is slowly added a solution of (S)-2-phenylalkanoic acid (4,27 g, 26.0 mmol) in THF (40 ml) at 0°C. the Mixture was stirred until then, until stopped the formation of gas. A solution of iodine (6.60 g, 26.0 mmol) in THF (40 ml) was then slowly added at 0°C. After addition, the resulting mixture was allowed to warm to room temperature and mixed for 1 hour. The reaction solution is then slowly poured into a solution of 1 N HCl (280 ml) and the resulting mixture was diluted with EtOAc (250 ml). The aqueous layer was extracted with EtOAc (150 ml × 3), and the combined organic layers are then washed with saturated NaHCO3(aq.), 0.5 M Na2S2O3(aq.) and salt solution. This organic solution was dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product. Purification using flash chromatography on silica gel (petroleum ether: EtOAc 4:1) was obtained the desired product 40 in the form of a colorless oil in quantitative yield. HPLC tR5,24 minutes

Example 40 Synthesis of compound 41 (S)-1-mesilate-phenylbutane

To a mixture of 40 (3,9 g, 26.0 mmol) and triethylamine (5.5 ml, to 39.5 mmol) in DCM (0 ml) is slowly added a solution of methanesulfonamide (4,47 g, to 39.0 mmol) in DCM (30 ml) at 0°C. After addition, the resulting mixture was allowed to warm to room temperature and was stirred for 2 hours. 1 N HCl (70 ml) is then added to the above mixture, and the aqueous layer was extracted with DCM (1×70 ml). The combined organic layers were washed with brine (150 ml), dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product 41 in the form of a colorless oil. This crude product was used in the next step without additional purification. HPLC tR6.48 in minutes

Example 41 Synthesis of compound 42 (S)-1-azido-2-phenylbutane

Suspension 41 (5,93 g, 26.0 mmol) and sodium azide (5.7 g, 78,0 mmol) in DMF (60 ml) was heated at 85°C for 3 hours. After cooling to room temperature the mixture was diluted with H2O (200 ml) and was extracted with EtOAc (250 ml). The organic layer is then washed H2O (4×150 ml)and then with brine (150 ml), dried over MgSO4that was filtered and concentrated under reduced pressure to obtain the crude product. Purification using flash chromatography on silica gel (100% petroleum ether as eluent) received net product 42 (a 4.03 g, 88%) in the form of a colorless oil. HPLC tRto 7.67 minutes

Example 42 Synthesis of compound 43 (S)-2-phenylethylamine

A mixture of 42 (4.0 g, of 22.8 mmol) and Lindlar catalyst (1.5 g) in EtOAc (50 ml) which was at room temperature under H2(40 psi) overnight. The mixture then was filtered through a pad of Celite, and the filtrate was concentrated under reduced pressure to obtain the crude product 43 (3.4 g, 100%) in the form of a light yellow oil. This crude product was used for conjugated addition reactions without additional purification. MS (ESI) 150 (M+1); HPLC tR1,84 minutes

Example 43 Synthesis of compound 44 allyl 2-(methoxy(methyl)amino)-2-oxoethylidene

To Alloc(allyloxycarbonyl)-glycine (1.45 g, 9.1 mmol) in DCM (20 ml) was added a THIEF reagent (3.3 grams, 7,46 mmol) and DIPEA (1.5 ml, about 10.7 mmol). After stirring at room temperature for 10 min was added N,O-dimethylhydroxylamine (0.8 g, 8.2 mmol) and DIPEA (1.5 ml, about 10.7 mmol). The reaction was stirred at room temperature overnight. DCM was removed using rotary evaporation, and the residue is absorbed in EtOAc (100 ml). The organic phase is washed H2O (3×100 ml), saturated sodium bicarbonate solution (3×50 ml), H2O (3×50 ml), 1M hydrochloric acid (3×50 ml), with brine (3×50 ml). The organic phase was dried (MgSO4) and the EtOAc was removed, to obtain the amide Weinrebe 44 in the form of white solids (0,43 g, 23%).

Alternatively, tert-butyl 2-(methoxy(methyl)amine is)-2-oxoethylidene 16 (Boc-Gly amide Weinrebe, 1.4 g, 6.4 mmol) in DCM (5 ml) and TFA (3 ml) was stirred at room temperature for 1 hour. The solvent was removed under reduced pressure, followed by addition of DCM (20 ml) and then DIPEA before the main. The solution was cooled to 0°C and added allylchloroformate (1,4 ml of 13.2 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was neutralized 1M hydrochloric acid and was extracted with EtOAc. EtOAc was removed using rotary evaporation, and the residue was subjected to column chromatography on silica gel using petroleum ether:EtOAc (1:1-0:1), providing 44 (0,86 g, 66%).

Example 44 Synthesis of compound 45 allyl 2-exabot-3-talkabout

To Amida Weinrebe 44 (of 0.43 g, 2.1 mmol) in DCM (5 ml) at 0°C was added vinylmania (10 mmol) in THF (10 ml). The reaction was stirred for 2 hours and examined using HPLC. The reaction was added to a mixture of ice and 1M hydrochloric acid (100 ml). The aqueous mixture was extracted with DCM (3×50 ml) and washed 1M hydrochloric acid (2×100 ml) and H2O (3×50 ml). The organic phase was dried (MgSO4) and the volume reduced to 50 ml using rotary evaporation. α,β-Unsaturated ketone 45 kept and used in solution without further purification.

Example 45 Synthesis of compound 46 (S)-9-fluorenylmethyl 10-(3,5-dichlorobenzyl)-2,2-dimethyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-treatises-19-ene-8-ylcarbamate

To 3,5-dichloraniline (0,49 g, 2.8 mmol) in DCM (5 ml) was added α,β-unsaturated ketone 45 (2,12 mmol) in DCM (10 ml). After stirring at room temperature for 15 min, was added Fmoc-diaminobutane acid(Vos)-HE (1.35 g, 3.1 mmol) and DIC (0.5 ml, 3.2 mmol). The reaction was stirred at room temperature overnight. DCM was removed using rotary evaporation, and the residue was subjected to column chromatography on silica gel using petroleum ether:EtOAc (1:1-0:1), affording Compound 46 (0,48 g, 22%).

Example 46 Synthesis of compound 47 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-(allyloxycarbonyl)-1-(3,5-dichlorobenzyl)-1,4-diazepan-2-it

To Compound 46 (0,48 g, to 0.63 mmol) in DCM (3 ml) was added diethylamine (1.5 ml). The reaction was stirred at room temperature for 1 hour. DCM and diethylamin removed using rotary evaporation. Added DCM (5 ml), triacetoxyborohydride sodium (0.2 g, were 0.94 mmol)and the reaction was stirred overnight at room temperature. The organic phase is washed with saturated sodium bicarbonate solution (25 ml), dried (MgSO4) and DCM was removed to obtain cyklinowanie product 47 (0.24 g, 72%).

Example 47 Synthesis of compound 48 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-aminomethyl-1-(3,5-dichlorobenzyl)-1,4-diazepan-2-it

To cyklinowanie products is at 47 (0.24 g, 0.45 mmol) in DCM (3 ml) was added 1,3-dimethylbarbituric acid (13 mg, 0.08 mmol) and palladium tetranitroaniline (5 mg). The reaction was pumped and stirred at room temperature for 1 hour. DCM was removed under reduced pressure to obtain the crude product 48 (0.15 g, 75%)which was used in subsequent reactions without purification.

Example 48 Synthesis of compound 49 (3S,5S)-3-(2-amino-ethyl)-5-(2-naphthylamine)-1-(3,5-dichlorobenzyl)-1,4-diazepan-2-it

To amine 48 (0.05 mg, 0.11 mmol) in DCM (1 ml) was added DIPEA (0.1 ml, 0.7 mmol), THIEF reagent (0.05 mg, 0.11 mmol) and 2-naphthoic acid (0.04 mg, 0.23 mmol). The reaction was stirred at room temperature for 2 hours. TFA (1 ml) was added and the reaction was stirred at room temperature for 2 hours. Rotary evaporation and preparative HPLC got 49 (48 mg, 90%). MS (ESI) 499,3 (M+1); HPLC tR5,77 minutes

Example 49 Synthesis of compound 50 N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naphthalene-2-sulfonamida

Prepared from allyl 2-exabot-3-talkabout 45, Boc-L-Arg(Fmoc)2-OH and 2,2-diphenylethylamine according to the methods of Examples 46-48, with the following modification: the First group TFA was removed during the method of removing the protective groups/cyclization of Example 47, rather than the use of diethylamine for Fmoc removal. Alloc removing the protective groups by the method of Example 48, the free amine was dissolved in DCM, to which was added naphthalene-2-sulphonylchloride (10 mg) and DIPEA (20 μl) and the reaction was stirred for 2 hours at room temperature. Diethylamine (1 ml) was added and stirred overnight to remove the Fmoc protection, and the reaction evaporated until dry. Preparative HPLC got named connection 50 (13 mg). MS (ES1) 613,5 (M+1); HPLC tRof 5.89 minutes

Example 50 Synthesis of compound 51 (S)-9-fluorenylmethyl 10-(2-ethylbutyl)-2,2-dimethyl-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-trasaction-8-ylcarbamate

2-ethylbutylamine (0.15 g, 1.48 mmol) in DCM (10 ml) was added α,β-unsaturated ketone 27 (1,47 mmol) in DCM (30 ml). After stirring at room temperature for 15 min was added Fmoc-diaminobutane acid(Vos)-HE (0.95 g, of 2.16 mmol) and DIC (0,34 ml, 2,19 mmol). The reaction was stirred at room temperature overnight. DCM was removed using rotary evaporation, and the residue was subjected to column chromatography on silica gel using petroleum ether:EtOAc (1:1-0:1), affording Compound 51 (0.5 g, 46%).

Example 51 Synthesis of compound 52 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-(benzyloxycarbonylamino)-1-(2-ethylbutyl)-1,4-diazepan-2-it

To Compound 51 (0.5 g, 0.67 mmol) in DCM (3 ml) was added diethylamine (1.5 ml). The reaction was stirred at room themes is the temperature value for 1 hour. DCM and diethylamin removed using rotary evaporation. DCM (5 ml) and triacetoxyborohydride sodium (0.2 g, were 0.94 mmol) was added and the reaction was stirred overnight at room temperature. The organic phase is washed with saturated sodium bicarbonate solution (25 ml), dried (MgSO4) and DCM was removed to obtain the crude cyklinowanie product 52 (0.4 g).

Example 52 Synthesis of compound 53 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-(aminomethyl)-1-(2-ethylbutyl)-1,4-diazepan-2-it

To cyklinowanie product 52 (0.4 g) in methanol (5 ml) was added catalytic Pd/C. the Reaction was stirred under atmosphere of hydrogen overnight. The reaction mixture was filtered through Celite and the methanol was removed via rotary evaporation to obtain Amin 53 (0.17 g, 68% from 51).

Example 53 Synthesis of compound 54 N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naphthalide

To Amin 53 (0,030 g, 0.08 mmol) in DCM (1 ml) was added DIPEA (0.1 ml, 0.7 mmol), THIEF reagent (0.03 g, 0.07 mmol) and 2-naphthoic acid (0.025 g, 0.14 mmol). The reaction was stirred at room temperature for 2 hours. TFA (1 ml) was added and the reaction was stirred at room temperature for 2 hours. Rotary evaporation and preparative HPLC received Connection 54 (23 mg, 68%). MS (ESI) 425,7 (M+1); HPLC tR5,27.

Example 54 Synthesis of compound 55 (3S,5S)-3-[2-(piperidine-1-yl)ethyl]-5-(benzyloxycarbonylamino)-1-(2-ethylbutyl)-1,4-diazepan-2-it

To the Connection 54 (0.25 g, 0.5 mmol) in DCM (3 ml) was added TFA (1.5 ml), the solution stirred at room temperature for 1 hour. Added DCM (20 ml) and the solution washed with saturated sodium bicarbonate solution (20 ml), dried over MgSO4and boiled away to obtain the crude amine (0.16 g). To this was added DMF (0.25 ml), potassium carbonate (10 mg) and 1,5-dibromethane (0.35 ml, 2.5 mmol). The reaction mixture was stirred at room temperature for 1.5 hours, then was added DCM (20 ml), the organic layer was washed with saturated sodium bicarbonate solution (20 ml) and H2O (20 ml), dried (MgSO4and boiled away to obtain the crude 55, which was used in subsequent reactions without purification.

Example 55 Synthesis of compound 56 (3S,5S)-3-[2-(piperidine-1-yl)ethyl]-5-aminomethyl-1 -(2-ethylbutyl)-1,4-diazepan-2-it

To cyklinowanie product 55 (0.4 g) in methanol (5 ml) was added catalytic Pd/C. the Reaction was stirred under atmosphere of hydrogen overnight. The reaction mixture was filtered through Celite and the methanol was removed via rotary evaporation to obtain the amine 56 (0.12 g).

Example 56 Synthesis of compound 57 2-ethyl-3-methylbutane-1-amine

A solution of 3,3-dimethylacrylic acid (2.00 g, 20 mmol) in THF (30 ml) was added dropwise to a solution of LDA (lithium Hai is propylamide) (44 mmol) in THF/hexane (60 ml) at -78°C. After heating up to -10°C and stirring for 20 min the reaction was re-cooled to -78°C. and added a solution of ethyliodide (6,86 g, 44 mmol)in THF (30 ml). The reaction was allowed to warm to room temperature overnight. To the resulting dark orange solution was added 1 M HCl until acidic. The organic layer was separated, washed H2O and brine solution, dried (MgSO4), was filtered and was concentrated to obtain a brown oil, 2-ethyl-3-methylbut-3-ene acid (is 3.08 g), which was used crude in the next reaction. To restore the acid groups of the crude product was dissolved in THF (70 ml) and cooled to 0°C. To this was added LiAlH4(2280 mg, 60 mmol). Mixing was obtained 2.7 g of pale yellow oil, which was purified flash chromatography (silica gel, 10% EtOAC in pet. ether) to obtain 1.70 g of 2-ethyl-3-methylbut-3-EN-1-ol in the form of oil. Alcohol (560 mg, 4,91 mmol) was turned into mesilate by dissolution in DCM (25 ml) at 0°C, then added MsCl (675 mg, 5.9 mmol), then with the help of Et3N (595 mg, 5.9 mmol). After 30 min the reaction was separated between DCM and 0.1 N HCl, the aqueous layer was extracted with DCM (2×)and the combined organic fractions and washed with brine, filtered and concentrated to obtain 200 mg of a pale yellow oil. The crude mesilate (4,91 mmol) was dissolved in acetonitrile (20 ml) and NaN3(957 mg, 14.7 mmol) is bavili. After 1 hour, was added DMF (6.5 ml) and the reaction was heated to boiling for 3 hours, then cooled. EtOAc (40 ml) and NaHCO3solution was added and the organic layer washed H2O (2×), with brine (1×) and dried, then was filtered to obtain a pale yellow solution of 3-(azidomethyl)-2-methylpent-1-ene, which was used crude in subsequent reactions. Suspension azide (4,91 mmol) in 50 ml of EtOAC was first made at 40 psi over Lindlar catalyst (460 mg) for 16 hours, then was filtered through Celite to leave a colourless solution. Flash chromatography (silica gel, 1-5% Meon in DCM) were called 120 mg of pure amine 57, with an additional 95 mg of material with impurities.

Example 57 Synthesis of compound 58 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-[benzyloxycarbonyl(methylamino)methyl]-1-(2,2-diphenylether)-1,4-diazepan-2-it

Prepared from Cbz-Sar, 2,2-diphenylethylamine and Fmoc-L-Orn(Boc) according to the methods of Examples 26-29.

Example 58 Synthesis of compound 59 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-(methylamino)methyl-1-(2,2-diphenylether)-1,4-diazepan-2-it

Cyklinowanie product 58 (1.9 grams) was dissolved in methanol (10 ml) with catalytic Pd/C and was hydrogenosomal under an atmosphere of hydrogen (40 psi) overnight. The reaction mixture was filtered through Celite and the methanol was removed using rotational the evaporation to obtain the amine 59 (1.86 g, 97%).

Example 59 Synthesis of compound 60 N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo-N-methyl-2-naphthalide

Amin 59 combined with 6-bromo-2-naphthoic acid, then took off the protective group with TFA according to Example 31. Rotary evaporation and preparative HPLC gave 60 (7.8 mg). MS (ESI) 629,4 (M+1); HPLC tR6,27 minutes

Example 60 Synthesis of compound 61 (3S,5S)-3-(tert-butoxycarbonylamino)-5-(6-bromo-2-naftopidil)-1-(2,2-diphenylether)-1,4-diazepan-2-it

Prepared from 2,2-diphenylethylamine, Fmoc-L-Orn(Boc) and 6-bromo-2-naphthoic acid according to the methods of Examples 29-32, without the step of removing TFA protective groups of Example 31.

Example 61 Synthesis of compound 62 N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-4-methyl-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo-2-naphthalide

Compound 61 (20,8 mg) was dissolved in DMF (1 ml) and treated with methyliodide (6 ml) at room temperature for 1 week. Added additional methyliodide (0.5 ml) and K2CO3and the reaction left at room temperature for another 2 days. Added TFA (2 ml) and the reaction was stirred at room temperature for 2 hours. Rotary evaporation followed by evaporation under high vacuum, then preparative HPLC received 62 (8.5 mg). MS (ESI) 629,3 (M+1); HPLC tR 6,22 minutes

Example 62 Synthesis of compound 63 N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naphthalide

Derived from 9, 2,2-diphenylethylamine and Fmoc-L-Orn(Boc) according to Examples 10-12. The first group was removed under standard conditions to obtain the free amine. MS(ESI) 535 (M+1); HPLC tR5,78 minutes

Example 63 Synthesis of compound 64 N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naphthalide

Amin 63 (0,79 g, 1.48 mmol), 1,5-dibromethane (0.2 ml, 1.48 mmol) and K2CO3(0,79 g) in DMF (11 ml) was stirred at room temperature for 4 hours. The resulting mixture was diluted with ethyl acetate (30 ml), washed H2O (5×30 ml), brine solution (10 ml) and dried over MgSO4. Purification by preparative HPLC received 64 (0,23 g, 25%) MS(ESI) 603,3 (M+1); HPLC tR6,04 minutes

Example 64 Synthesis of compound 65 N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-(isopropylamino)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naphthalide

To a stirred mixture of the amine 63 (11 mg, 0.02 mmol), acetone (2 ml) and MgSO4(50 mg) in DCM (5 ml) was added triacetoxyborohydride sodium (8.5 mg, 0.04 mmol) at room temperature. Stirring is continued for 2 hours, the mixture was concentrated, re-dissolved in EtOAc (5 ml), washed with saturated aqueous solution of the m NaHCO 3(10 ml) and with brine (10 ml), dried over MgSO4and concentrated under reduced pressure. Purification by preparative HPLC gave 65 (9.5 mg, 80%). MS(ESI) 577,2 (M+1); HPLC tR5,97 minutes

Example 65 Synthesis of compound 66 tert-butyl (methylamino)(methylthio)methyltyramine

DIAD (aminobutiramida azodicarboxylate) (2,7 ml of 13.8 mmol) was added to a stirred mixture of thiopseudourea (2.0 g, 6,9 mmol), PPh3(3.6 g, of 13.8 mmol) and Meon (0,55 ml of 13.8 mmol) in dry THF (5 ml) at 0°C under nitrogen. Stirring was continued at 0°C for 3 hours, then at room temperature for 16 hours. The solvent was removed under reduced pressure and the resulting residue re-dissolved in EtOAc, washed with saturated aqueous solution of NaHCO3(20 ml) and with brine (20 ml), and dried over MgSO4. Purification by silikagelevye chromatography using 20% EtOAc in petroleum ether as eluent received 66 (1.63 g, 78%) in the form of a colorless oil. MS(ESI) 305 (M+1); HPLC tR7,97 minutes

Example 66 Synthesis of compound 67 N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-(3-methylguanine)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naphthalide

A mixture of Compound 63 (10 mg, 0.019 mmol), guanylurea substances 66 (56,9 mg, 0,19 mmol) and DIPEA (6,6 µl of 0.038 mmol) in DCM (5 ml) was stirred at room temperature is over 16 hours. Added TFA (5 ml)and the resulting mixture was stirred at room temperature for 30 minutes the Solvent was removed under reduced pressure, and the crude product was purified by preparative HPLC to obtain 67 (0.53 mg, 4.7%) in the form of a white solid. MS(ESI) 591,3 (M+1); HPLC tR5,94 minutes

Example 67 Synthesis of compound 68 (S)-9-fluorenylmethyl 1-phenyl-10-(2,2-diphenylether)-18,18-dimethyl-4,9,13,16-tetraoxo-2,17-dioxa-4,10,15-triethanolamine-8-ylcarbamate

To a stirred mixture of Fmoc-L-Orn(Cbz)-OH (1.78 g, 3.65 mmol), DIPEA (of 0.64 ml, 3.65 mmol) and HATU (1.39 g, 3.65 mmol) in DCM (10 ml) was added a solution of amine 17 at room temperature. Stirring is continued for 3 hours, the reaction mixture was washed with a saturated aqueous solution of NaHCO3(20 ml) and with brine (20 ml), and dried over MgSO4. The solvent was removed under reduced pressure the crude 68 used in the next step without additional purification. MS(ESI) 853 (M+1); HPLC tR9,90 minutes

Example 68 Synthesis of compound 69 (S)-(N-fluoren-9-yl)methyl 7-((4-(tert-butoxycarbonylamino)-3-oxobutyl)(2.2-diphenylether)carbarnoyl)-3-methyl-1,3-diazepan-1-carboxylate

A mixture of 68 (136 mg, strength of 0.159 mmol) and Pd/C (20 mg) in ethanol (5 ml) under which H2at 30 psi for 16 hours, then was filtered, concentrated under reduced is the t, to get the crude amine (90 mg, 78%). Amine (90 mg, 0.125 mmol) was treated with excess formaldehyde solution in H2O (37 mmol) in Meon (5 ml), followed by triacetoxyborohydride sodium (23,5 mg, the 0.375 mmol). After 1 hour the reaction mixture was washed with a saturated aqueous solution of NaHCO3(10 ml) and with brine (10 ml), dried over MgSO4that was filtered and concentrated. The crude material was used in the next step without additional purification. MS (ESI) 745 (M+1); HPLC tR7,83 minutes

Example 69 Synthesis of compound 70 (S)-(N-fluoren-9-yl)methyl 7-((4-(2-naptime)-3-oxobutyl)(2.2-diphenylether)-carbarnoyl)-3-methyl-1,3-diazepan-1-carboxylate

Compound 69 (8 mg, to 0.011 mmol) was treated with a mixture of 1:1 volume/volume triperoxonane acid/DCM (2 ml) for 30 min at room temperature. The mixture was concentrated under reduced pressure, re-dissolved in DCM (5 ml), washed with saturated aqueous solution of NaHCO3(5 ml) and with brine (5 ml), dried over MgSO4and was filtered. The filtrate is then treated with a mixture of 2-naphthoic acid (1.8 mg, to 0.011 mmol), DIPEA (5,7 μl, 0,033 mmol) and the THIEF (4,8 mg, to 0.011 mmol) in DCM (1 ml) with stirring at room temperature. After 3 hours the reaction mixture was washed with a saturated aqueous solution of NaHCO3(10 ml) and with brine (10 ml), dried over MgSO4Professor is literaly and concentrated. The crude material was used in the next step without additional purification. MS(ESI) 799 (M+1); HPLC tRof 7.90 minutes

Example 70 Synthesis of compound 71 N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-(methylamino)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naphthalide

To a mixed solution of 70 (to 0.011 mmol) in DCM (5 ml) was added diethylamine (5 ml) at room temperature. The reaction was stirred for 1 hour, then concentrated under reduced pressure. The residue re-dissolved in DCM (5 ml), then added triacetoxyborohydride sodium (5 mg, 0.08 mmol) at room temperature. Stirring is continued for 1 hour and the resulting mixture washed with saturated aqueous NaHCO3(10 ml) and with brine (10 ml), dried over MgSO4, filtered and concentrated. Purification by preparative HPLC received 71 (0.21 mg) in the form of a white solid. MS(ESI) 549,3 (M+1); HPLC tR5,93 minutes

Example 71 Synthesis of compound 72 (S)-2-(allyloxycarbonyl)-3-(naphthalene-2-yl)propanoic acid

To a stirred mixture of L-3-(2-naphthyl)allingitalia (5.0 g, to 19.8 mmol), Na2CO3(7,3 g and 69.3 mmol) and 1,4-dioxane (30 ml) in H2O (50 ml) was added allylchloroformate (2,1 ml of 19.8 mmol) at 0°C. the Resulting mixture was stirred for 16 hours, then concentrated is under reduced pressure. The residue was diluted with ethyl acetate (50 ml)and at 0°C was acidified to pH 2. The aqueous phase was extracted with ethyl acetate (3×20 ml), the combined organic phase was washed H2O (50 ml) and with brine (20 ml), dried over MgSO4that was filtered and concentrated under reduced pressure to obtain 72 in the form of a colorless oil (5.8 g, 97%)which was used in the next step without additional purification. HPLC tR6,60 minutes

Example 72 Synthesis of compound 73 (S)-allyl 1-(methoxy(methyl)amino)-3-(naphthalene-2-yl)-1-oxoprop-2-ylcarbamate

To a stirred mixture of the acid 72 (of 5.84 g of 19.5 mmol), DIPEA (3,7 ml of 2.09 mmol) and the THIEF (8,63 g of 19.5 mmol) in DCM (10 ml) was added a pre-mixed solution of N,O-dimethylhydroxylamine (1.9 grams, of 19.5 mmol) and DIPEA (7.3 ml, to 41.6 mmol) in DCM (10 ml) at room temperature. Stirring is continued for 16 hours, the reaction mixture was washed 1N HCl (3×60 ml), H2O (3×60 ml), saturated aqueous NaHCO3(3×60 ml) and with brine (60 ml), dried over MgSO4. Purification by silikagelevye chromatography using 20% ethyl acetate in petroleum ether as eluent received 73 (4.83 g, 71%) in the form of a colorless oil. MS (ESI) 343 (M+1); HPLC tR7,07 minutes

Example 73 Synthesis of compound 74 (S)-allyl 1-(naphthalene-2-yl)-3-oxopent-4-EN-2-ylcarbamate

At 0°C solution of vinylmania in THF (11.5 ml, 1 M) was added in one portion to the amide Weinrebe 73 (1,58 g, to 4.62 mmol) under nitrogen with stirring. The resulting mixture was allowed to mix for 2 hours, and poured into a mixture of 1N HCl/ice (50 ml). The aqueous mixture was extracted with DCM (3×20 ml), the combined DCM extract was washed in 1 N HCl (50 ml), saturated aqueous NaHCO3(50 ml) and with brine (20 ml), dried over MgSO4. The solvent was removed under reduced pressure, producing the product 74 (1,14 g, 80%)which was used in the next step without additional purification. MS (ESI) 310 (M+1); HPLC tR7,51 minutes

Example 74 Synthesis of compound 75 (S)-allyl 5-(2,2-diphenylethylamine)-1-(naphthalene-2-yl)-3-oxopent-2-ylcarbamate

To a stirred solution of 2,2-diphenylethylamine (0.45 g, 2.3 mmol) in DCM (55 ml) was added vinylmation 74 (0.71 g, 2.3 mmol) in one portion. Stirring is continued for 2 hours with the reaction mixture used in the next step without purification. MS (ESI) 507 (M+1); HPLC tR7,22 minutes

Example 75 Synthesis of compound 76 (S)-allyl 5-(N-(BOC-L-Arg(Cbz)2) 2,2-diphenylethylamine)-1-(naphthalene-2-yl)-3-oxopent-2-ylcarbamate

To a stirred solution of the amine adduct 75 (2.3 mmol) was added to a mixture of BOC-Arg(Cbz)2-OH (1.25 g, 2.3 mmol), DIPEA (0.8 ml, 4.6 mmol) and HATU (0.87 g, 2.3 mmol) in DCM (15 ml) and room temperature. Stirring is continued for 16 hours after which the reaction mixture is washed with a saturated aqueous solution of NaHCO3(3×20 ml) and with brine (10 ml), then dried over MgSO4. Purification by silikagelevye chromatography using 20% ethyl acetate in petroleum ether as eluent got 76 in the form of a colorless oil (708 mg, 30% over 3 steps). MS (ESI) 1031 (M+1); HPLC tR10,80 minutes

Example 76 Synthesis of compound 77 allyl (S)-1-((3S,5RS)-1-(2,2-diphenylether)-3-(bis Cbz 3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl ka RLA Mat

To a stirred solution of the acyclic intermediate 76 (0,48 g, 0.47 mmol) in DCM (5 ml) was added TFA (5 ml) at room temperature. Stirring was continued for 30 min, after which the mixture was diluted with DCM (20 ml), then washed with a saturated aqueous solution of NaHCO3(3×20 ml) and with brine (10 ml) and dried over MgSO4. The resulting solution was added triacetoxyborohydride sodium (0.2 g, were 0.94 mmol) with stirring at room temperature, after 30 minutes the mixture was washed with a saturated aqueous solution of NaHCO3(3×20 ml) and with brine (10 ml), then dried over MgSO4. Untreated 77, a mixture of diastereomers in diazepan-2-Ohe C5 was used in the next step without additional purification. MS (ESI) 915 (M+1)

Example 77 Synthesis soedineniya bis (Cbz) 1-(3-((2S,7RS)-7-((S)-1-amino-2-(naphthalene-2-yl)ethyl)-4-(2,2-diphenylether)-3-oxo-1,4-diazepan-2-yl)propyl)guanidine

A mixture of compound 77 (36 mg, 0,039 mmol), 1,3-dimethylbarbituric acid (7.4 mg, 0,047 mmol) and Pd(PPh3)4in DCM (5 ml) was stirred at room temperature under vacuum for 4 hours. The resulting mixture was used in the next step without additional purification. MS (ESI) 832 (M+1)

Example 78 Synthesis of compounds 79 and 80 N-((S)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)ndimethylacetamide and N-((S)-1-((3S,5R)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)ndimethylacetamide

A solution of amine 78 (0.09 mmol) in DCM (5 ml) was treated with acetic anhydride (8,6 μl, 0.09 mmol) with stirring at room temperature. After 3 hours the mixture was concentrated, re-dissolved in EtOAc, washed with saturated aqueous solution of NaHCO3(10 ml) and with brine (10 ml), dried over MgSO4, then concentrated under reduced pressure. The residue was dissolved in Meon (10 ml), was added Pd/C (5 mg), and the solution was under which H2at 20 psi for 16 hours. The reaction was filtered, concentrated and purified by preparative HPLC to obtain the preferred diastereoisomer 79 (3 mg) and less preferred diastereoisomer 80 (6 mg) in the form of white solids.

79: MS (ESI) 606,4 (M+1); HPLC tR UAH 6,033 min

80: MS (ESI) 606,3 (M+1); HPLC tR6,046 min

Example 79 Synthesis of compounds 81 and 82 (S)-2-acetamido-N-((S)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)-3-(1H-imidazol-5-yl)propanamide and (S)-2-acetamido-N-((S)-1-((3S,5R)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)-3-(1H-imidazol-5-yl)propanamide

To a stirred mixture of Ac-L-His-OH (33.6 mg, 0,156 mmol), DIPEA (112,5 μl, 0,312 mmol) and a THIEF (of 68.8 mg, 0,156 mmol) in DMF (1 ml) was added amine 78 (0,039 mmol) at room temperature. Stirring was continued for 16 hours, then the reaction mixture was diluted with a mixture of DCM/H2O (10 ml, 1:1 volume/volume), and the aqueous phase was extracted with DCM (3×5 ml). The combined DCM extracts were washed with saturated aqueous solution of NaHCO3(3×20 ml) and with brine (10 ml), dried over MgSO4, and concentrated under reduced pressure. The residue re-dissolved in Meon (5 ml) and added Pd/C (20 mg). The resulting mixture which was under the H2at 30 psi for 16 hours, then was filtered, concentrated and purified by preparative HPLC to obtain the preferred diastereoisomer 81 (1.9 mg) and less preferred diastereoisomer 82 (0.9 mg) in the form of white solids.

81: MS (ESI) 743,4 (M+1); HPLC tR5,489 min

82: MS (ESI) 743,4 (M+1); HPLC t R5,555 min

Example 80 Synthesis of compounds 83 and 84 propyl (S)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethylcarbamate and propyl (S)-1-((3S,5R)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethylcarbamate

A mixture of 77 (36 mg, 0,039 mmol) and Pd/C (5 mg) in the Meon (5 ml) which was under H2 at 20 psi for 16 hours, then was filtered, concentrated and purified by preparative HPLC to obtain the preferred diastereoisomer 83 (0.07 mg) and less preferred diastereoisomer 84 (2.7 mg) in the form of white solids.

83: MS (ESI) 650,3 (M+1); HPLC tRof 6.52 min

84: MS (ESI) 650,2 (M+1); HPLC tR6,64 min

Example 81 Synthesis of compounds 85-87 1-(3-((2S,7S)-7-(N-R1 (R)-1-amino-2-(naphthalene-2-yl)ethyl)-4-(2,2-diphenylether)-3-oxo-1,4-diazepan-2-yl)propyl)guanidine

Connection 85-87 were prepared in the same manner as the preferred diastereomers of Compounds 79, 81 and 83 by means of the methods described in Examples 71-80 D-(2-naphthyl)alrightalright as source material.

ConnectionR1groupMS (M+1)tR(min)
85Ac606,26,01
86Ac-His743,55,41
87Propylenecarbonate650,46.42 per

Examples 82-90: Syntheses by scheme 2: Preparation of all four diastereomers of N-((1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naphthalide 88

Example 82 Synthesis of compound 89 2,2-dimethyl-10-(2,2-diphenylether)-4,7,11-trioxo-3,12-dioxo-5,10-diazapentane-14-ene

2.2-Diphenylethylamine (3 g) was added to BOC-vinylketones 16 (2.8 g)as in Example 18. To the crude adduct 17 added Alloc-Cl (1.6 ml) and the reaction was stirred until until TLC (thin layer chromatography) showed consumption of secondary amine. THE solvent is boiled away, and the residue was purified column chromatography (SiO2gel, pet. ether/EtOAc) to obtain 3.2 g (57%) 89.

Example 83 Synthesis of compound 90 (S)-allyl 2-amino-5-(benzyloxycarbonylamino)pentanoate L-H-Orn(Cbz)-Ollila

H-L-Orn(Cbz)-OH (6,66 g, 25 mmol), allyl alcohol (17,56 ml, 25 mmol) and p-TsOH (5.7 g, 30 mmol) was dissolved in benzene (200 ml) and boiled the reflux under conditions of Dean-stark for 5 hours. A large part of the solvent was then distilled, the remaining part was removed under vacuum. The resulting solid was recrystallize from DCM, filtered and dried to obtain 11,19 g (94%) salt tosilata. To obtain the free amine solid was dissolved in DCM, washed us. NaHCO3, the aqueous layer was washed DCM (3×)and the organic layers were dried over MgSO4and boiled away the dryness.

Example 84 Synthesis of compound 91 (R)-allyl 2-amino-5-(benzyloxycarbonylamino)pentanoate O-N-Orn(Cbz)-Ollila

H-D-Orn(Cbz)-OH (6,66 g, 25 mmol) was turned into of 10.93 g (91%) salt tosilata 91 as in Example 83, then turned into a free amine.

Example 85 Synthesis of compound 92 (2R)-allyl 5-(benzyloxycarbonylamino)-2-(10-(2,2-diphenylether)-2,2-dimethyl-4,11-dioxo-3,12-dioxo-5,10-diazapentane-14-EN-7-ylamino)pentanoate

Protected aminoketone 89 (746 mg, 1.6 mmol), D-Orn(Cbz)-Ollil 91 (538 mg, of 1.76 mmol) and NaBH(SLA)3(678 mg, 3.2 mmol) in a minimum volume of DCM was stirred for 24 hours. Added drop Asón directly before working at this level was added saturated NaHCO3extracted DCM (3×)and the organic extracts combined and washed with saturated NaHCO3and H2O, dried over MgSO4and boiled away the dryness. The product was purified column chromatography (SiO2the gel is et. the air/EtOAc) to obtain 890 mg (74%) of 92 as a mixture of diastereoisomers.

Example 86 Synthesis of compound 93 (2S)-allyl 5-(benzyloxycarbonylamino)-2-(10-(2,2-diphenylether)-2,2-dimethyl-4,11-dioxo-3,12-dioxo-5,10-diazapentane-14-EN-7-ylamino)pentanoate

L-Orn(Cbz)-Ollil 90 (592 mg, of 1.93 mmol) was turned into a mixture of various diastereomers 93 (925 mg, 76%)following the methods of Example 85.

Example 87 Synthesis of compounds 94 and 95 (3R,5S)-5-(N-Boc aminomethyl)-3-(N-Cbz 3-aminopropyl)-1-(2,2-diphenylether)-1,4-diazepan-2-she (3R,5R)-5-(N-Boc aminomethyl)-3-(N-Cbz 3-aminopropyl)-1-(2,2-diphenylether)-1,4-diazepan-2-it

Alloc/allyl-protected derivative 92 (840 mg, 1.11 mmol) was dissolved in minimum amount of DCM. Added 1,3-dimethylbarbituric acid (346 mg, 2.22 mmol) and catalytic Pd(PPh3)4and the reaction was degirolami under vacuum, was sealed and stirred overnight. The reaction was diluted to 50 ml DCM, was added DIPEA (430 mg of 3.33 mmol) and the THIEF (540 mg, 1,22 mmol)and the reaction was stirred for 30 minutes DCM was removed under vacuum, and the residue is absorbed in EtOAc, washed (saturated NaHCO3H2O, saturated NaCl), dried (MgSO4and boiled away the dryness (TLC: EtOAc, 2 spots, Rfof 0.33 and 0.57). Two diastereomeric product was separated by column chromatography (SiO2gel, pet. ether/EtOAc) to obtain 362 mg the wound is lirovannomu (3R,5S) isomer 94, and 342 mg later lirovannomu (3R,5R) isomer 95.

Example 88 Synthesis of compounds 96 and 97 (3S,5R)-5-(N-Boc aminomethyl)-3-(N-Cbz 3-aminopropyl)-1-(2,2-diphenylether)-1,4-diazepan-2-she (3S,5S)-5-(N-Boc aminomethyl)-3-(N-Cbz 3-aminopropyl)-1-(2,2-diphenylether)-1,4-diazepan-2-it

(3S,5R) (312 mg) and (3S,5S) (331 mg) isomers obtained from L-Orn-derived acyclic material 93 (870 mg), following the procedure of Example 87.

Example 89 Synthesis of compounds 98-101 5-(N-Boc aminomethyl)-3-(N,N'-Cbz23-guanidinopropionic)-1 -(2,2-diphenylether)-1,4-diazepan-2-it

Orn Cbz group 94 was removed by hydrogenation (H2, 30 psi) above the catalytic Pd/C in methanol overnight. The solution was filtered through Celite, and boiled away to obtain a solid substance. The solution of the resulting amine (187 mg, 0,39 mmol) in DCM was mixed with a solution guanylurea reagent CbzNHC(=NCbz)NHTf (196 mg, 0.43 mmol) in DCM. Added the TEA triethylamine (43 mg, 0.43 mmol)and the reaction was stirred overnight. The solution was diluted with DCM, washed (KHSO4, us. NaHCO3, brine), dried (MgSO4and boiled away the dryness, then purified using flash chromatography on SiO2using hexane/EtOAc as eluent to obtain (3R,5S) 98 (182 mg, 59%). Other isomers 95-97 turned in a similar way to obtain:

99 (3R,5R): 171 mg (68%) of the 148 mg Amin

100 (3S,5S): 80 mg (65%) is C 72 mg Amin

101 (3S,5R):142 mg (58%) of 144 mg Amin

Example 90 Synthesis of compounds 102-105

102 N-(((3R,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

103 N-(((3R,5R)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

104 N-(((3S,5R)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

105 N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime

Boc derivative 99 (180 mg) in DCM (1 ml) was treated with TFA (1 ml) in 20 ml. of Solvent was removed by evaporation, was added a solution of NaHCO3, and was extracted with 3× DCM. The dichloromethane solution was dried over MgSO4that was filtered and boiled away the dryness. Portion (56 mg, 0,086 mmol) of the crude amine with the corresponding protective groups in DCM was stirred with 2-naphthoic acid (16 mg), DIPEA (60 μl) and the THIEF (42 mg) for 30 minutes Meon added and the reaction was stirred overnight. The reaction was filtered, then purified using flash chromatography on SiO2using petroleum ether/EtOAc as eluent to obtain (3R,5R) isomer (43 mg, 94%). Other isomers are transformed in a similar way to obtain: (3R,5S): 41 mg (85%) of 60 mg 98, (3S,5R): 27 mg (70%) of 40 mg 101, and (3S,5S): 13 mg (74%) of 20 mg 100

Each connection process is or dioxane:Meon and was first made over catalytic Pd/C at 30 psi H 2the whole night. The solution was filtered through Celite, and boiled away to obtain a solid substance. 102 (3R,5S): 27 mg (96%) of 41 mg, 103 (3R,5R): 25 mg (85%) of 43 mg, 104 (3S,5R): 11 mg (quantitative) of 13 mg and 105 (3S,5S): 3 mg (73%) of 6 mg

ConnectionstereochemistryMS (M+1)tR(min)
102(3R,5S)577,45,775
103(3R,5R)577,55,750
104(3S,5R)577,55,783
105(3S,5S)577,35,787

Example 91 Synthesis of compounds 406, 526, 541-546

406 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

526 6-chloro-N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

541 6-chloro-N-(((3R,5R)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

542 6-chloro-M-(((3S,5R)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,diazepan-5-yl)methyl)-2-naptime

543 6-chloro-N-(((3R,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

544 6-chloro-N-(((3S,5R)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

545 6-chloro-N-(((3R,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

546 6-chloro-N-(((3R,5R)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime

Connection 406, 526 and 541-546 prepared by following similar methods as used for the preparation of Compounds 102-104 (path Scheme 2). In addition, the connection 406, 526, 541 and 546 prepared according to the path diagram 1; detailed method for the preparation of Compounds 406 contained in the Examples 92-99.

6,265
ConnectionstereochemistryMS (M+1)tR(min)
406(3S,5S,2'S)575,36,269
526(3S,5S,2'R)574,8
541(3R,5R,2'R)575,46,404
542(3S,5R,2'S)575,26,262
543(3R,5S,2'S)575,26,110
544(3S,5R,2'R)575,16,211
545(3R,5S,2'R)575,26,253
546(3R,5R,2'S)575,46,274

Example 92 Synthesis of compound 547 (S)-N-(2-oxo-4-(2-phenylethylamine)butyl)-3-phenylpropanamide

To a solution of (S)-phenylethylamine (8.5 g, 57,07 mmol) in DCM (100 ml) was added a solution of α,β-unsaturated ketone 27 (12.5 g, to 57.1 mmol) in DCM (100 ml) at room temperature in one portion. The resulting mixture was stirred until then, until all α,β-unsaturated ketones has not trashdolls (within one hour), then the conjugate adduct accession 547 was used directly in subsequent reactions. HPLC tR5,71 min, MS (ESI) 369,3 (M+)

Example 93 Synthesis of compounds 548 (S)-9-fluorenylmethyl 10-[(S)-2-phenylbutyl]-2,2-dimethyl-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-trasaction-8-ylcarbamate

To a freshly prepared amine 547 in DCM (200 ml) was added Fmoc-L-Dab(Boc) - OH (32.7 g, to 74.2 mmol), followed by DIPC (11.5g, to 74.2 mmol) at room temperature. The resulting mixture was stirred for 2 hours, a byproduct of Diisopropylamine removed by means of filtration through a pad Celite®and the filtrate was concentrated under reduced pressure to obtain the crude product, which was purified by silikagelevye column chromatography using 30-70% EtOAc/petroleum spirit as eluent to obtain 548 (19.9 g, 44% yield over two steps). TLC tR0,23 (50% EtOAc/petroleum spirit), HPLC tRthere is a 10.03 min, MS (ESI) 791,2 (M+1)

Example 94 Synthesis of compounds 549 (S)-10-[(S)-2-phenylbutyl]-2,2-dimethyl-8-amino-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-trasaction

Diethylamine (30 ml) was added to the solution of the acylated amine 548 (19.9 g, 25,19 mmol) in DCM (30 ml) at room temperature and the resulting mixture was stirred for 30 minutes, the Solvent and diethylamin removed under reduced pressure to obtain the target product 549. It was used in the next step without additional purification. HPLC tR6,85 min MS (ESI) 569,3 (M+)

Example 95 Synthesis of compounds 550 (3S,5S)-3-(2-tert-butoxycarbonylamino)-5-(benzyloxycarbonylamino)-1-[(S)-2-phenylbutyl]-1,4-diazepan-2-it

To a solution of the crude Fmoc material removed protective groups 549 in DCM (50 ml) was added Asón (15 ml), then NaBH(SLA)3(5.34 g, to 25.2 mmol) in one portion at room temperature. The resulting mixture was stirred for 30 min, then washed with saturated solution of NaHCO3(aq.) (80 ml × 3), brine solution (80 ml) and dried over MgSO4. Filtration and concentration of the organic phase under reduced pressure, the obtained crude product, which was purified using silikagelevye column chromatography using 50-100% EtOAc/petroleum spirit, then 20% MeCN/EtOAc to obtain the product 550 (12.3 g, 88% over two steps). TLC tR0,19 (70% EtOAc/petroleum spirit), HPLC tR7,06 min, MS (ESI) 553,3 (M+1)

Example 96 Synthesis of compounds 551 tert-butyl 2-{(2S,7S)-7-aminomethyl-3-oxo-4-[(S)-2-phenylbutyl]-1,4-diazepan-2-yl}ethylcarbamate

A mixture of Cbz-protected product 550 (12.3 g, of 22.3 mmol) and 5% Pd/C (2 g) in Meon (100 ml) which was at room temperature under hydrogen at atmospheric pressure for one hour. The mixture then was filtered through a pad of Celite®and the filtrate was concentrated under reduced pressure to obtain the crude AMI is and 551. The crude material was used in the next step without additional purification. HPLC tR5,77 min MS (ESI) 419,3 (M+1)

Example 97 Synthesis of compounds 552 tert-butyl 2-((2S,7S)-7-((6-chloro-2-naptime)methyl)-3-oxo-4-((S)-2-phenylbutyl)-1,4-diazepan-2-yl)ethylcarbamate

To a solution of free amine 551 and 6-chloro-2-naphthoic acid (4,58 g of 22.3 mmol) in DCM (125 ml) was added diisopropylethylamine (7,74 ml of 44.5 mmol) and the THIEF (9,84 g of 22.3 mmol) at room temperature. The resulting mixture was stirred for 16 hours, then DCM was removed under reduced pressure. The remainder is swallowed up in EtOAc (80 ml), then washed with saturated NaHCO3(aq.) (100 ml × 5), brine solution (100 ml) and dried over MgSO4. Filtration and concentration of the organic phase obtained crude material, which was purified using silikagelevye column chromatography using 80-100% EtOAc/petroleum spirit as eluent to obtain the product 552 (10.7 g, 79%). TLC tR0,31 (80% EtOAc/petroleum spirit), HPLC tR7,66 min, MS (ESI) 607,2 (M+1)

Example 98 Synthesis of compound 441 N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-6-chloro-2-naphthalide

To the Boc-protected material 552 (10.7 g, 17.6 mmol) in DCM (26 ml) was added TFA (26 ml) in one portion, the resulting mixture was stirred at room temperature for one hour. DCM UDA is or under reduced pressure, and the remainder is swallowed up in EtOAc (30 ml), washed with saturated NaHCO3(aq.) (30 ml × 3), brine solution (30 ml) and dried over MgSO4. Filtration and concentration of the organic phase under reduced pressure, the obtained crude amine 441, which was used in the next step without additional purification.

HPLC tR5,98 min

MS (ESI) 507,0 (M+1)

Example 99 Synthesis of compound 406 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naphthalide

To a mixture of the crude amine 441 in CH3CN (800 ml) was added 1,5-dibromethane (23.9 ml, 175,7 mmol), then K2CO3(48.6 g, 351,4 mmol). The resulting mixture was stirred at room temperature for 44 hours, was observed using HPLC for the conversion of sm (6,0 min) in the product (6,4 min)avoiding continued during the reaction, leading to parallelomania for education brompheniramineodeine the by-product of 7.1 min). During isolation, excessive heat/concentration of the crude solution should be avoided before removing excess dibromopropane to avoid parallelomania piperidino rings. To2CO3removed by means of filtration through a pad Celite®and the filtrate washed with white spirit (800 ml × 2). Phase MeCN was concentrated under reduced pressure to 400 ml, and washed the white STI is item (400 ml × 2). MeCN additionally concentrated under reduced pressure to 200 ml, and washed with white spirit (200 ml × 2). Evaporation final rinse white spirit showed that were extracted no more than 1.5-dibromethane, so that the phase of MeCN was concentrated under reduced pressure.

Aminopropyl-functionalized TLC rf of 0.05-0,47 (80% EtOAc/white spirit)

Analytical HPLC tR6,41 min, MS (ESI) 575,2 (M+1).

The crude product was purified using a combination of flash-column chromatography through aminopropyl-functionalized silica gel and/or by recrystallization from acetonitrile.

Flash-column: the column is filled aminopropyltriethoxysilane silica gel (154 g) in 20% ethyl acetate/white-spirit, downloaded the crude free base oil (7.2 g). The column was suirable 20% ethyl acetate/white spirit (150 ml), followed by 50% ethyl acetate/petroleum spirit (150 ml), 80% ethyl acetate/petroleum spirit (150 ml × 2), 100% ethyl acetate (150 ml) and, ultimately, 100% acetonitrile (150 ml). The fractions containing 406, were combined and evaporated to dryness to obtain a white crystalline solid.

Crystallization: White crystalline solid (2,87 g), obtained by column purification, was dissolved in boiling acetonitrile (50 ml) of 85°C. Activated carbon (Darco® G-60, -100 mesh, Sigma-Aldrich) (200 mg) was added to remove colored impurities. EXT the wheelie additional portion of acetonitrile (50 ml), and the resulting mixture was heated to boiling for 5 minutes the charcoal was filtered while the solution was hot filtered with paper and charcoal, rinsed with hot acetonitrile (25 ml). Pure solution of acetonitrile was reduced to 50 ml and left to stand to cool to room temperature for 16 hours. White crystals were filtered off and dried by suction to get 2,22 g (99.0% purity by HPLC analysis). Additional 117,2 mg (93,3% purity) received an additional crystallization from the filtrate.

The transformation in l salt: Free base (2,4229 g, 42.1 mmol) suspended in 1:1 mixture of acetonitrile and milliQ H2O (10 ml). A solution of 1 M HCl (aq.) added up until not dissolve all solids (approximately 5 ml). Additional amount of milliQ H2O then added (20 ml) and the resulting solution was frozen and liofilizirovanny all night, leading to a white powder (2,61 g, 95.6% of the output).

HPLC (6,27 min, MS (ESI) 575,1 (M+1),1H NMR (600 MHz, CDCl3): δ 0.75 in (t, 3H, J=7,2 Hz), 1,40 (m, 1H), and 1.56 (m, 1H), 1,65 (m, 1H), 1,76-1,90 (m, 4H), 1,90 e 2.06 (m, 2H), 2.13 in (m, 1H), 2,30 (br, 1H), 2.57 m (m, 1H), 2,64-of 2.86 (m, 4H), 2,90-3,10 (m, 2H), 3,25 (dd, 1H, J=15,2, 10,4 Hz), 3,53 (m, 2H), 3,70-of 3.85 (m, 3H), 4.00 points (m, 2H), 4,10 (dd, 1H, J=13,6, and 5.6 Hz), of 4.45 (m, 1H), 7,10 (d, 2H, J=7,2 Hz), 7,18 (t, 1H, J=7,2 Hz), 7,26 (t, 1H, J=7,2 Hz), 7,37 (dd, 1H, J=9,0, 1,8 Hz), 7,71 (d, 1H, J=8,4 Hz), of 7.75 (s, 1H), 7,86 (d, 1H, J=9,0 Hz), of 8.09 (d, 1H, J=9,0 Hz), 8,64 (s, 1H), 8,68 (m, 1H), 9,85 (br, 1H).

13C NMR (100 MHz, CDCl3): δ 1,78, 21,86, 23,08 (2), 24,59, 26,14, 28,09, 42,01, 46,24, 47,22, 53,14, 53,53, 54,03, 56,74, 57,79, 61,96, 125,35, 126,24, 126,89, 127,20, 127,33, 127,85, 128,51, 128,72, 130,69, 130,76, 130,91, 133,48, 135,28, 142,29, 167,18, 167,74

Example 100 Synthesis of compounds 540 6-chloro-N-(([5,6,6-2H3](3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)[2H2]methyl)-2-naphthalide

Connection 540 synthesized according to the procedures in Examples 92-99, except that the steps of removing the Fmoc protective groups/reductive amination of Examples 94 and 95 were replaced by the following methods for the introduction of deuterium atoms.

To a solution of (S)-9-fluorenylmethyl 10-[(S)-2-phenylbutyl]-2,2-dimethyl-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-trasaction-8-ylcarbamate 548 (370,5 mg, 0.47 mmol) in dry THF (7.5 ml) was added dry triethylamine (7.5 ml, 54 mmol) in one portion at room temperature and then D2O (of 99.96 atom. % deuterium, 3.0 ml, 168 mmol). This mixture was stirred under nitrogen at room temperature for 16 hours using the reaction mixture in the next step without isolation. MS (ESI) 573,0 (M+1), tR6.95 minutes.

To the crude reaction mixture of materialmen added NaBD3CN (152 mg, 2,31 mmol) in one portion, the reaction was stirred at room temperature for 24 hours. Added an additional portion of NaBD3CN (182,4 mg, or 3.28 mmol) and stirring continued at room the Oh temperature for 24 hours. The reaction was quickly cooled by the addition of saturated NaHCO3(aq.) and water mixture, extracted EtOAc (3 × 10 ml × 3). The combined organic extracts washed with brine (15 ml), dried over MgSO4and concentrated in vacuo. Flash chromatography (60% EtOAc/petroleum spirit) gave the product (175,8 mg, 67%). TLC Rf0,32 (70% EtOAc/petroleum spirit). Analytical HPLC tR7,06 min; MS (ESI) m/z 558,0 (M+1), 559,0, 557,0, 560,0.

Example 101 Synthesis of compounds 106-540.

Connection 106-540, with deputies, as identified in table 1 were obtained as in the previous examples, according to the ways identified in schemes 1-5, as summarized in table 2, with the experimental properties are summarized in table 4.

Table 1:
The identity of connections
Connection.R1XR2R3YZN(R4a)(R4b)W
142-naphtolNN CH2(CH2)3NHC(=NH)NH23,5-dichlorobenzyl
256-fluoro-2-naphtolNNCH2(CH2)2N(CH2CH3)22.2-diphenylether
316-fluoro-2-naphtolNNCH2(CH2)2NH22.2-diphenylether
334-chlorocinnamoylNNCH2(CN2)2(1-piperidinyl)2.2-diphenylether
372-naphtolNNCH2(CH2)2NH22-phenylbutyl
382-naphtolNN CH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
392-naphtolNNCH2(CH2)2(1-piperidinyl)(R)-2-phenylbutyl
492-naphtolNNCH2(CH2)2NH23,5-dichlorobenzyl
502-naphthylmethylNNCH2(CH2)2NHC(=NH)NH22.2-diphenylether
542-naphtolNNCH2(CH2)2NH22-ethylbutyl
606-bromo-2-naphtolMe NCH2(CH2)3NH22.2-diphenylether
626-bromo-2-naphtolNMeCH2(CH2)3NH22.2-diphenylether

Connection.R1XR2R3YZN(R4a)(R4b)W
632-naphtolNNCH2(CH2)3NH22.2-diphenylether
642-naphtolNNCH2(CH2)3(1-piperidinyl)2.2-diphenylether
65 2-naphtolNNCH2(CH2)3NHCH(CH3)22.2-diphenylether
672-naphtolNNCH2(CH2)3NHC(=NH)NHMe2.2-diphenylether
712-naphtolNNCH2(CH2)3NHMe2.2-diphenylether
79acetylNN(S)-SSN2-(2-naphthyl)(CH2)3NHC(=NH)NH22.2-diphenylether
81Ac-L-HisNN(S)-SSN2-(2-naphthyl)(CH2)3NHC(=NH)NH2 2.2-diphenylether
83propylenecarbonateNN(S)-SSN2-(2-naphthyl)(CH2)3NHC(=NH)NH22.2-diphenylether
85acetylNN(R)-SSN2-(2-naphthyl)(CH2)3NHC(=NH)NH22.2-diphenylether
86Ac-L-HisNN(R)-CHCH2-(2-naphthyl)(CH2)3NHC(=NH)NH22.2-diphenylether
87propylenecarbonateNN(R)-SSN2-(2-naphthyl)(CH2)3NHC(=NH)NH22.2-diphenylether
1052-naphtolN NCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1064-biphenylcarboxylicNNCH2(CH2)3NH22.2-diphenylether
107indole-2-carbonylNNCH2(CH2)3NH22.2-diphenylether

Connection.R1XR2R3YZN(R4a)(R4b)W
1084-biphenylcarboxylicHHCH2(CH2)3NHC(=NH)NH2 2.2-diphenylether
109indole-2-carbonylHHCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1102-naphthylacetylHHCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1111,2,3,4-tetrahydro-2-naphtolHHCH2(CH2)3NHC(=NH)NH22.2-diphenylether
112the quinoline-3-carbonylHHCH2(CH2)3NHC(=NH)NH22.2-diphenylether
113cinoxacin-2-carbonylHHCH2(SN 2)3NHC(=NH)NH22.2-diphenylether
114isoquinoline-3-carbonylHHCH2(CH2)3NHC(=NH)NH22.2-diphenylether
115benzoylHHCH2(CH2)3NHC(=NH)NH22.2-diphenylether
116ginaldiHHCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1172-naphtolHHCH2(CH2)4NH21-naphthylmethyl
1182-naphthylacetylHHCH2 (CH2)4NH21-naphthylmethyl
1191-naphtolHHCH2(CH2)4NH21-naphthylmethyl
120indole-3-acetylHHCH2(CH2)4NH21-naphthylmethyl
1214-biphenylaceticHHCH2(CH2)4NH22-naphthylmethyl
1222-naphtolHHCH2(CH2)4NH22-naphthylmethyl
1232-naphthylacetylHHCH2(CH2) 4NH22-naphthylmethyl
1241-naphtolHHCH2(CH2)4NH22-naphthylmethyl
1251-naphthylacetylHHCH2(CH2)4NH22-naphthylmethyl
1262-naphtolHHCH2(CH2)4NH22.2-diphenylether
127S-TicHHCH2(CH2)4NH22.2-diphenylether
128R is TicHHCH2(CH2)4NH2 2.2-diphenylether
1292-benzofuranylHHCH2(CH2)4NH22.2-diphenylether
130R is TicHHCH2(CH2)3NHC(=NH)NHMe2.2-diphenylether
131S-TicHHCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1322-benzofuranylHHCH2(CH2)3NHC(=NH)NH22.2-diphenylether

N
Connection.R1XR2R3YZN(R 4a)(R4b)W
133indan-2-carbonylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
134R is TicNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
135benzothiophen-2-carbonylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1362,4-dichlorobenzoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1372.5-dichlorobenzoylNNCH2 (CH2)3NHC(=NH)NH22.2-diphenylether
138benzoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
139cyclohexanolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1403-phenoxybenzoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1414-phenoxybenzoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
142indole-2-carbonylNNCH 2(CH2)3NHC(=NH)NH22.2-diphenylether
1433-phenyl-propanolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1443,4-dimethylbenzoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1454-tert-butylbenzoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1462,4-dimethoxybenzoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
147cyclohexylethylN NCH2(CH2)3NHC(=NH)NH22.2-diphenylether
148piperonylicNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
149the benzimidazole-5-carbonylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
150benzotriazol-5-carbonylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
151CyclopentanolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1523,4-dichlorobenzoylNCH2(CH2)3NHC(=NH)NH22.2-diphenylether

Connection.R1XR2R3YZN(R4a)(R4b)W
153TRANS-cynnamoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1543,5-dichlorobenzoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1552,4-dichloro-phenylacetylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1561-methoxy-2-naphtolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1573,4-dichloro-phenylacetylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
158b-methoxy-2-naphtolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1592,4-dichloro-cynnamoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
160adamantane-1-carbonylNNCH2(CH2)3NHC(=NH)NH2 2.2-diphenylether
161phenoxyacetylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1623-methoxy-2-naphtolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1634-bromobenzoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
164S-benzodioxan-2-carbonylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1654-chlorocinnamoylNNCH2(CH2) 3NHC(=NH)NH22.2-diphenylether
1663-(2-thienyl)acryloylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
167R-benzodioxan-2-carbonylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1684-hydroxycinnamicNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1692-methoxycinnamylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1704-methylcinnamicNN CH2(CH2)3NHC(=NH)NH22.2-diphenylether

With unitsR1XR2R3YZN(R4a)(R4b)W
1712-trifluoromethyl-cynnamoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1723-forcenameNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
173alpha-methyl the cynnamoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
174TRANS-2-fenil klonopin-1-carbonyl NNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1752,4-dichloro-PHENOXYACETICNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1763-chlorocinnamoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1771,3-benzothiazole-6-carbonylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1785-phenyl-2-furoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
3-methoxycinnamylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1806-bromo-2-naphtolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1812-naphtolNNCH2(CH2)3NHC(=NH)NH2phenethyl
1822-naphtolNNCH2(CH2)3NHC(=NH)NH23,4-dichlorophenacyl
1832-naphtolNNCH2(CH2)3NHC(=NH)NH22,4-dichlorophenacyl
184benzothiophen-5-carbonylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1853-methyl-2-phenyl-pyrazole-4-carbonylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1864-methoxycinnamylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether

Connection.R1XR1R3YZN(R4a)(R4b)W
1876-fluoro-2-naphtolNNCH2(CH2)sub> 3NHC(=NH)NH22.2-diphenylether
1882-chlorocinnamoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1892-hydroxycinnamicNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1903-methylcinnamicNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1913-trifluoromethyl-cynnamoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1923-hydroxycinnamicNN(CH2)3NHC(=NH)NH22.2-diphenylether
1932-forcenameNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1942-methylcinnamicNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
195alpha forcenameNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1962-naphtolNNCH24-piperidinyl2.2-diphenylether
1972-naphtolNN CH2CH2(4-piperidinyl)2.2-diphenylether
1984-forcenameNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
1994-trifluoromethyl-cynnamoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
2002-naphtolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylpropyl
2012-naphtolNNCH2(CH2)3NHC(=NH)NH2cyclohexylmethyl
2022-naphtolNN CH2(CH2)3NHC(=NH)NH21-adamantane-methyl
2032-naphtolNNCH2(CH2)3NHC(=NH)NH2(S)-1,1-diphenyl-2-propyl
2042-naphtolNNCH2(CH2)3NHC(=NH)NH2(R)-1,1-diphenyl-2-propyl
2052-naphtolNNCH2(CH2)3NHC(=NH)NH2cyclohexyl

N
Connection.R1XR2R3YZN(R4a)(R4b)W
2062-naphtolNCH2(CH2)3NHC(=NH)NH2(R)-1,1-diphenyl-1-fluoro-2-propyl
2072,6-divertinglyNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
2082-chloro-6-forcenameNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
2094-bromocinnamylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
2104-amoxicillinamoxilNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
211 6-brominatorNNCH2(CH2)3NH22.2-diphenylether
212TRANS-cynnamoylNNCH2(CH2)3NH22.2-diphenylether
2134-chlorocinnamoylNNCH2(CH2)3NH22.2-diphenylether
2141,4-dimethoxy-2-naphtolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
2152-naphtolNNCH2(CH2)3NHC(=NH)N(Me)22.2-diphenylether
216 b-hydroxy-2-naphtolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
217b-amino-2-naphtolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
2184-IU the cynnamoylNNCH2(CH2)3NH22.2-diphenylether
2194-fluorine cynnamoylNNCH2(CH2)3NH22.2-diphenylether
220b-fluoro-2-naphtolNNCH2(CH2)3NH22.2-diphenylether
2212-ethylhexanoylNNCH2(CH2)3NH22.2-diphenylether
2223,4-dimethylbenzoylNNCH2(CH2)3NH22.2-diphenylether
2233,4-dimethylbenzoylNNCH2(CH2)3NH22.2-diphenylether
2242-ethylhexanoylNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
2252-naphtolNNCH2(CH2)3NH(cyclohexyl)2.2-diphenylether

Connection.R1XR2R3YZN(R4a)(R4b)W
2262-naphtolNNCH2(CH2)3NHC(=NH)NH22-naphthyl
2272-naphtolNNCH2(CH2)3NHC(=NH)NH2(9-fluorenyl)methyl
2284-forcenameNNCH2(CH2)3NH(cyclohexyl)2.2-diphenylether
2292-naphtolNNCH2(CH2)4NHCH(CH3)2 2.2-diphenylether
2302,4-divertinglyNNCH2(CH2)3NH22.2-diphenylether
2314-cyanocinnamicNNCH2(CH2)3NH22.2-diphenylether
2323-(2-naphthyl)acryloylNNCH2(CH2)3NH22.2-diphenylether
2334-fluoro-phenoxyacetylNNCH2(CH2)3NH22.2-diphenylether
2345-(4-chlorophenyl)-2-furoylNNCH2 (CH2)3NH22.2-diphenylether
2354-(pyrrol-1-yl)-benzoylNNCH2(CH2)3NH22.2-diphenylether
2362-oxo-1-phenyl-pyrrolidin-3-carbonylNNCH2(CH2)3NH22.2-diphenylether
2375-(4-chlorophenyl)-isoxazol-3-carbonylNNCH2(CH2)3NH22.2-diphenylether
2385-(2-furyl)-isoxazol-3-carbonylNNCH2(CH2)3NH22.2-diphenylether
2392-phenyl-4-diazocarbonylN NCH2(CH2)3NH22.2-diphenylether
2404-(3,5-dimethyl-1H-pyrazole-1-yl)benzoylNNCH2(CH2)3NH22.2-diphenylether

258
Connection.R1XR2R3YZN(R4a)(R4b)W
2413-methyl-2-phenyl-pyrazole-4-carbonylNNCH2(CH2)3NH22.2-diphenylether
2422-naphtolNNCH2(CH2)3NHC(=NH)NH2cyclohexanethiol
243 2-naphtolNNCH2(CH2)3NHC(=NH)NH22-norbornanyl
2442-naphtolNNCH2(CH2)3NHC(=NH)NH22,2-bis(4-methoxyphenyl)ethyl
2452-naphtolNNCH2(CH2)4NHCH2Ph2.2-diphenylether
2462-naphtolNNCH2(CH2)4NH(cyclopentyl)2.2-diphenylether
2472-naphtolNNCH2(CH2)4NH(cyclobutyl)2.2-diphenylether
248 2-naphtolNNCH2(CH2)4N(cyclobutyl)22.2-diphenylether
2492-naphtolNNCH2(CH2)3NHC(=NH)NH2benzil
2502-naphtolNNCH2(CH2)3NHC(=NH)NH22,2-bis(4-forfinal)ethyl
2512-naphtolNNCH2(CH2)3NHC(=NH)NH22-naphthalenethiol
2523-(5-methyl-2-thienyl)-acryloylNNCH2(CH2)3NH22.2-diphenylether
253 5-phenyl-pyrazole-3-carbonylNNCH2(CH2)3NH22.2-diphenylether
2544-forcenameMeNCH2(CH2)3NH22.2-diphenylether
2554-forcenameNMeCH2(CH2)3NH22.2-diphenylether
2564-(3-methyl-5-oxo-2-pyrazolin-1-yl)benzoylNNCH2(CH2)3NH22.2-diphenylether
2574-bromocinnamylNNCH2(CH2)3NH22.2-diphenylether
4-chlorocinnamoylNNCH2(CH2)3(1-pyrrolidinyl)2.2-diphenylether
2594-chlorocinnamoylNNCH2(CH2)3(1-piperidinyl)2.2-diphenylether
2602-naphtolNNCH2CH2CH2NH22.2-diphenylether

td align="center"> 2.2-diphenylether
Connection.R1XR2R3YZN(R4a)(R4b)W
2612-naphtolNNCH2(CH2)3(1-pyrrolidinyl) 2.2-diphenylether
2622-naphtolNNCH2(CH2)3NHC(=NH)NH22.2-diphenylether
2632-naphtolNNCH2(CH2)3NHC(=NH)NH21-naphthalenethiol
2642-naphtolNNCH2(CH2)3NHC(=NH)NH22-(2-naphthyl)ethyl
2652-naphtolNNCH2(CH2)3NHC(=NH)NH2(S)-CH2CH(Ph)NHCOMe
266TRANS-cynnamoylNNCH2(CH2)3(1-piperidinyl) 2.2-diphenylether
2673,4-dimethylbenzoylNNCH2(CH2)3(1-piperidinyl)2.2-diphenylether
2683,4-dichlorobenzoylNNCH2(CH2)3(1-piperidinyl)2.2-diphenylether
2692-naphtolNNCH2(CH2)3NHC(=NH)NH2(S)-CH2CH(Ph)NH-COcBu
2702-naphtolNNCH2CH2(CH2)3NHC(=NH)NH2(S)-CH2CH(Ph)-NHCOcHex
2712-naphtolNNCH2CH2NH2/sub> 2.2-diphenylether
2724-chlorocinnamoylNNCH2CH2NHz2.2-diphenylether
2734-forcenameNNCH2(CH2)2NH22.2-diphenylether
2744-methylcinnamicNNCH2(CH2)2NH22.2-diphenylether
2752-naphtolNNCH2CH2(1-piperidinyl)2.2-diphenylether
2764-chlorocinnamoylNNCH2CH2(1-piperidinyl)
2773,4-dichlorobenzoylNNCH2(CH2)2NH22.2-diphenylether
2783,4-dimethylbenzoylNNCH2(CH2)2NH22.2-diphenylether
279TRANS-cynnamoylNNCH2(CH2)2NH22.2-diphenylether
2804-chlorocinnamoylNNCH2(CH2)2NH22.2-diphenylether
2813,4-dichlorobenzoylNNCH2(CH2)2(1-piperidinyl 2.2-diphenylether

Connection.R1XR1R3YZN(R4a)(R4b)W
2823,4-dimethylbenzoylNNCH2(CH2)2(1-piperidinyl)2.2-diphenylether
283TRANS-cynnamoylNNCH2(CH2)2(1-piperidinyl)2.2-diphenylether
2844-forcenameNNCH2(CH2)2(1-piperidinyl)2.2-diphenylether
2854-methylcinnamicNN CH2(CH2)2(1-piperidinyl)2.2-diphenylether
2862-naphtolNNCH2(CH2)3NHC(=NH)NH23,5-dimethylbenzyl
2872-naphtolNNCH2(CH2)3NHC(=NH)NH2(S)-CH2CH(Ph)NHCOPh
2882-naphtolNNCH2(CH2)3NHC(=NH)NH2(R)-CH2CH(Ph)NHCOPh
2892-naphtolNNCH2(CH2)3NHC(=NH)NH2CH2CH(Ph)OMe
2902-naphtolNN(CH2)3NHC(=NH)NH2CH2CH(Ph)OnPr
2912-naphtolNNCH2(CH2)3NHC(=NH)NH2CH2CH(Ph)OBn
2922-naphtolNNCH2(CH2)3NHC(=NH)NH2CH2CH(Ph)Ollil
2934-methylcinnamicNNCH2(CH2)3NHCOCH32.2-diphenylether
2944-methylcinnamicNNCH2(CH2)3NHCO(cyclohexyl)2.2-diphenylether
2952-naphtolNN CH2(CH2)3NHC(=NH)NH2CH2CH(Ph)OPh
2962-naphtolNNCH2(CH2)3NHC(=NH)NH2CH2CH(Ph)CO2Et
2972-naphtolNNCH2(CH2)3NHC(=NH)NH22-ethylbutyl
2982-naphtolNNCH2(CH2)3NHC(=NH)NH23,5-dimethyl-cyclohexylmethyl
2994-chlorocinnamoylNNCH2(CH2)2NHCO(cyclohexyl)2.2-diphenylether
3004-chlorocinnamoylN NCH2(CH2)2NHCOCH2(cyclohexyl)2.2-diphenylether

Connection.R1XR2R3YZN(R4a)(R4b)W
301benzoylNN(CH2)2(CH2)2NH22.2-diphenylether
3023,4-dichlorobenzoylNN(CH2)2(CH2)2NH22.2-diphenylether
3032-naphtolNN(CH2)2(CH2)2NH22.2-diphenylether
304 benzoylNN(CH2)2(CH2)2(1-piperidinyl)2.2-diphenylether
3053,4-dichlorobenzoylNN(CH2)2(CH2)2(1-piperidinyl)2.2-diphenylether
3062-naphtolNN(CH2)2(CH2)2(1-piperidinyl)2.2-diphenylether
3072-naphtolNNCH2(CH2)3NHC(=NH)NH2CH2CH(Ph)CONMe2
3083,4-dichlorobenzoylNNCH2(CH2)2NH23,5-dichlorobenzyl
3094-chlorocinnamoylNNCH2(CH2)2NH23,5-dichlorobenzyl
3102-naphtolNNCH2(CH2)3NHC(=NH)NH23-chloro-5-terbisil
3112-naphtolNNCH2(CH2)3NHC(=NH)NH23,5-diferensial
3122-naphtolNNCH2(CH2)3NH23-chloro-5-terbisil
3132-naphtolNNCH2(CH2)3NH23,5-dipteran the Il
3142-naphtolNNCH2(CH2)3NH22.5-dichlorobenzyl
3152-naphtolNNCH2(CH2)3NH22,6-dichlorobenzyl
3162-naphtolNNCH2(CH2)3NH23,5-dimethoxybenzyl
3172-naphtolNNCH2(CH2)3NH22 chlorbenzyl
3182-naphtolNNCH2(CH2)3NH22,3-dichlorobenzyl
3192-naphtolNNCH2(CH2)3NH22,4-dichlorobenzyl
3202-naphtolNNCH2(CH2)3NH23,4-dichlorobenzyl
3212-naphtolNNCH2(CH2)3NH23-fluoro-5-methylbenzyl
3222-naphtolNNCH2(CH2)3NH23-fluoro-5-(trifluoromethyl)-benzyl

Connection.R1XR2R3YZN(R4a)(R4b) W
3232-naphtolNNCH2(CH2)3NH24-chlorbenzyl
3242-naphtolNNCH2(CH2)3NH22-phenylbutyl
3252-naphtolNNCH2(CH2)3NH21-(1-phenyl-cyclohexyl)-methyl
3263,4-dichlorobenzoylNNCH2(CH2)2(1-piperidinyl)3,5-dichlorobenzyl
3272-naphtolNNCH2(CH2)2(1-piperidinyl)3,dichlorobenzyl
3284-chlorocinnamoylNNCH2(CH2)2(1-piperidinyl)3,5-dichlorobenzyl
3293,4-dichlorobenzoylNNCH2(CH2)2NH22-ethylbutyl
3304-chlorocinnamoylNNCH2(CH2)2NH22-ethylbutyl
3314-chlorocinnamoylNNCH2(CH2)2(1-piperidinyl)2-ethylbutyl
3323,4-dichlorobenzoylNNCH2(CH2)2(1-piperidinyl) 2-ethylbutyl
3332-naphtolNNCH2(CH2)2(1-piperidinyl)2-ethylbutyl
3344-chloro-3-fluoro-benzoylNNCH2(CH2)2NH22-ethylbutyl
3354-chloro-3-methyl-benzoylNNCH2(CH2)2NH222-ethylbutyl
3363-chloro-4-fluoro-benzoylNNCH2(CH2)2NH22-ethylbutyl
3373-chloro-4-methyl-benzoylNNCH2(CH2)2NH2 2-ethylbutyl
3384-chlorocinnamoylNNCH2CH2(1-piperidinyl)2-ethylbutyl
3392-naphtolNNCH2(CH2)2(1-pyrrolidinyl)2.2-diphenylether
3402-naphtolNNCH2(CH2)3NH23,5-bis(trifluoromethyl)-benzyl
3412-naphtolNNCH2(CH2)3NH23 chlorbenzyl
3422-naphtolNNCH2(CH2)3(1-piperidinyl) 2-phenylbutyl
3432-naphtolNNCH2(CH2)3NHC(=NH)NH2CH2CH(Ph)CON[-(CH2)5-]

Connection.R1XR2R3YZN(R4a)(R4b)W
3442-naphtolNNCH2(CH2)3NHC(=NH)NH2CH2CH(Ph)CONHPh
3453,4-dichlorobenzoylNN(CH2)2(CH2)2NHCH(CH3)22.2-diphenylether
3463,4-dichlorobenzoylNN(With the 2)2(CH2)2N(CH(CH3)2)22.2-diphenylether
3473,4-dichlorobenzoylNNCH2CH2NH23,5-dichlorobenzyl
3482-naphtolNNCH2CH2NH23,5-dichlorobenzyl
3494-chlorocinnamoylNNCH2CH2NH23,5-dichlorobenzyl
3503,4-dichlorobenzoylNNCH2CH2(1-piperidinyl)3,5-dichlorobenzyl
3514-chlorocinnamoylNN CH2CH2(1-piperidinyl)3,5-dichlorobenzyl
3523,4-dichlorobenzoylNNCH2(CH2)2NH22-phenylbutyl
3534-chlorocinnamoylNNCH2(CH2)2NH22-phenylbutyl
3543,4-dichlorobenzoylNNCH2CH2(1-pyrrolidinyl)3,5-dichlorobenzyl
3552-naphtolNNCH2CH2(1-pyrrolidinyl)3,5-dichlorobenzyl
3562-naphtolNNCHsub> 2(CH2)3NH2(S)-β-methylphenethyl
3572-naphtolNNCH2(CH2)3NH2(R)-β-methylphenethyl
3582-naphtolNNCH2(CH2)2N(CH3)22.2-diphenylether
3596-fluoro-2-naphtolNNCH2(CH2)3(1-piperidinyl)2.2-diphenylether
3602-naphtolNNCH2(CH2)3NH23,5-diethylphenyl
3614-chlorocinnamoylNN CH2(CH2)2N(CH2CH3)22.2-diphenylether
3622-naphtolNNCH2(CH2)2N(CH2CH3)22.2-diphenylether
3633,4-dichlorobenzoylNNCH2(CH2)2(1-piperidinyl)(R)-2-phenylbutyl
3644-chlorocinnamoylNNCH2(CH2)2(1-piperidinyl)(R)-2-phenylbutyl
3654-chlorocinnamoylNNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl

Connection. R1XR2R3YZN(R4a)(R4b)W
3666-chloro-2-naphtolNNCH2(CH2)2NH22.2-diphenylether
3672-naphtolNNCH2(CH2)2(1-piperidinyl)2.2-diphenylether
3682-naphtolNNCH2(CH2)2(1-piperidinyl)2.2-diphenylether
3696-fluoro-2-naphtolNNCH2(CH2)2NH22-ethylbutyl
3706-chloro-2-on tail NNCH2(CH2)2NH22-ethylbutyl
3716-bromo-2-naphtolNNCH2(CH2)2NH22-ethylbutyl
3726-fluoro-2-naphtolNNCH2(CH2)2(1-piperidinyl)2-ethylbutyl
3736-chloro-2-naphtolNNCH2(CH2)2(1-piperidinyl)2-ethylbutyl
3746-bromo-2-naphtolNNCH2(CH2)2(1-piperidinyl)2-ethylbutyl
3753,4-d is chlorbenzoyl NNCH2(CH2)2NH23,5-dimethyl-cyclohexyl
3762-naphtolNNCH2(CH2)2NH23,5-dimethyl-cyclohexyl
3774-chlorocinnamoylNNCH2(CH2)2NH23,5-dimethyl-cyclohexyl
3786-chloro-2-naphtolNNCH2(CH2)2(1-piperidinyl)2.2-diphenylether
3796-fluoro-2-naphtolNNCH2(CH2)2(1-piperidinyl)2.2-diphenylether
380 4-chlorocinnamoylNNCH2(CH2)2(1-pyrrolidinyl)2.2-diphenylether
3814-chlorocinnamoylNNCH2(CH2)2NHCH(CH3)22.2-diphenylether
3822-naphtolNNCH2(CH2)2NHCH(CH3)22.2-diphenylether
3833,4-dichlorobenzoylNNCH2(CH2)2NHCH(CH3)22.2-diphenylether
3842-naphtolNNCH2(CH2)3NH22,6-dimethy the-cyclohexylmethyl
3852-naphtolNNCH2(CH2)3NH2(S)-2-phenylbutyl
3863,4-dichlorobenzoylNNCH2(CH2)2(1-piperidinyl)3,5-dimethyl-cyclohexylmethyl

Connection.R1XR2R3YZN(R4a)(R4b)W
3873,4-dichlorobenzoylNNCH2(CH2)2NHCH(CH3)23,5-dimethyl-cyclohexylmethyl
3882-naphtolNNCH2 (CH2)2NH23-methyl-2-phenylbutyl
3892-naphtolNNCH2(CH2)2NH2(S)-2-phenylbutyl
3902-naphtolNNCH2(CH2)3NH2(R)-2-phenylbutyl
3913-(4-chlorophenyl)-propanolNNCH2(CH2)2(1-piperidinyl)2.2-diphenylether
3923-(4-chlorophenyl)-propanolNNCH2(CH2)2NH22.2-diphenylether
3934-chlorocinnamoylNNCH2 CH2NHCO(2-pyridyl)2.2-diphenylether
3942-naphtolNNCH2(CH2)2(1-piperidinyl)(R)-3-methyl-2-phenylbutyl
3952-naphtolNNCH2(CH2)2(1-piperidinyl)(S)-3-methyl-2-phenylbutyl
3964-isopropylphenolNNCH2(CH3)2(1-piperidinyl)2.2-diphenylether
3974-isopropylphenolNNCH2(CH2)2NH22.2-diphenylether
3982,4-dimethylcarbamoylN NCH2(CH2)2(1-piperidinyl)2.2-diphenylether
3992,4-dimethylcarbamoylNNCH2(CH2)2NH22.2-diphenylether
4002,4-divertinglyNNCH2(CH2)2(1-piperidinyl)2.2-diphenylether
4012,4-divertinglyNNCH2(CH2)2NH22.2-diphenylether

Connection.R1XR2R3YZN(R4a)(R4b)W
402 4-chlorocinnamoylNHCH2CH2NHCO(cyclohexyl)2.2-diphenylether
4034-chlorocinnamoylNHCH2(CH2)2(4-morpholinyl)2.2-diphenylether
4044-chlorocinnamoylHHCH2(CH2)N[-C(Me)=CHCH=C(Me)-]2.2-diphenylether
4054-chlorocinnamoylHHCH2CH2CH2(2,5-dimethyl-2-pyrrolidin-1-yl)2.2-diphenylether
4066-chloro-2-naphtolHHCH2(CH3)2(1-piperidinyl)(S)-2-phenylbutyl
4074-chlorocinnamoylHHCH2(CH3)2(1-pyrrolidinyl)(S)-2-phenylbutyl
4084-chlorocinnamoylHHCH2(CH2)2NHCH(CH3)2(S)-2-phenylbutyl
4096-chloro-2-naphtolHHCH2(CH3)2(1-pyrrolidinyl)(S)-2-phenylbutyl
4103,4-dichlorobenzoylHHCH2(CH3)2(1-piperidinyl)(S)-2-phenylbutyl
4113,4-dichlorobenzoylHHCH2(CH3)2(1-piperidinyl)S)-2-phenylbutyl
412CbzHHCH2(CH3)2(1-piperidinyl)2.2-diphenylether
4134-bromocinnamylHHCH2(CH3)2(1-piperidinyl)2.2-diphenylether
4145-(4-chlorophenyl)-isoxazol-3-carbonylHHCH2(CH3)2(1-piperidinyl)2.2-diphenylether
4156-chloro-2-naphtolHHCH2(CH3)2(1-piperidinyl)(S)-2-phenylbutyl
4163,4-dichlorobenzoylHHCH2(CH3)2(1-piperidinyl) (S)-2-phenylbutyl
4176-chloro-2-naphtolHHCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
4183,4-dichlorobenzoylHHCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
4194-chlorocinnamoylHHC(Me)2(CH2)2NH22.2-diphenylether
4204-chlorocinnamoylHHC(Me)2(CH2)2(1-piperidinyl)2.2-diphenylether
4212-naphtolHHCH2(CH )2NH2(R)-2-(4-chlorophenyl)propyl

Connection.R1XR2R3YZN(R4a)(R4b)W
4222-naphtolNHCH2(CH2)2NH22-(4-chlorophenyl)propyl
4232-naphtolNHCH2(CH2)2(1-piperidinyl)(R)-2-(4-chlorophenyl)propyl
4242-naphtolHHCH2(CH2)2(1-piperidinyl)(S)-2-(4-chlorophenyl)propyl
4253,4-dichlorobenzoylHH CH2(CH2)2N(phenyl)(CH3)(S)-2-phenylbutyl
4263,4-dichlorobenzoylHHCH2(CH2)2N(CH2CH3)2(S)-2-phenylbutyl
4273,4-dichlorobenzoylHHCH2(CH2)2(4-morpholinyl)(S)-2-phenylbutyl
4283,4-dichlorobenzoylHHCH2(CH2)2NH(phenyl)(S)-2-phenylbutyl
4293,4-dichlorobenzoylHHCH2(CH2)2NH(benzyl)(S)-2-phenylbutyl
4303,4-dichlorobenzoyl HHCH2(CH2)2NHC(CH3)3(S)-2-phenylbutyl
4313,4-dichlorobenzoylHHCH2(CH2)2(4-CH3-piperazine-1-Il)(S)-2-phenylbutyl
4322-naphtolHHCH2(CH2)2(1-piperidinyl)(R)-2-fenilpentil
4332-naphtolHHCH2(CH2)2(1-piperidinyl)(S)-2-fenilpentil
434p-trifluoromethyl-benzoylHHCH2(CH2)2(1-piperidinyl)2.2-diphenylether
435 p-trifluoromethyl-benzoylHHCH2(CH2)2NH22.2-diphenylether
436m-trifluoromethyl-benzoylHHCH2(CH2)2(1-piperidinyl)2.2-diphenylether
437m-trifluoromethyl-benzoylHHCH2(CH2)2NH22.2-diphenylether
4386-chloro-2-naphtolHHCH2(CH2)2NHCH(CH3)23,5-dichlorobenzyl

W
Connection.R1XR2R3YZN(R4a)(R4b)
4393,4-dichlorobenzoylNHCH2(CH2)2NHCH(CH3)23,5-dichlorobenzyl
4406-chloro-2-naphtolNHCH2(CH2)2NHCH(CH3)2(S)-2-phenylbutyl
4416-chloro-2-naphtolHHCH2(CH2)2NH2(S)-2-phenylbutyl
4423,4-dichlorobenzoylHHCH2(CH2)2N(benzyl)CH3(S)-2-phenylbutyl
4433,4-dichlorobenzoylHHCH2(CH2)2(peep the Razin-1-yl) (S)-2-phenylbutyl
4443,4-dichlorobenzoylHHCH2(CH2)2N(n-pentyl)CH3(S)-2-phenylbutyl
4453,4-dichlorobenzoylHHCH2(CH2)2N[(CH(CH3)2]2(S)-2-phenylbutyl
4463,4-dichlorobenzoylHHCH2(CH2)2(4-CH3-piperidine-1-yl)(S)-2-phenylbutyl
4476-chloro-2-naphtolHHCH24-piperidinyl(S)-2-phenylbutyl
4486-chloro-2-naphtolHHCH2 1-isopentyl-4-piperidinyl(S)-2-phenylbutyl
4493,4-dichlorobenzoylHHCH2(CH2)2(3,5-Me2-piperidine-1-yl)(S)-2-phenylbutyl
4503,4-dichlorobenzoylHHCH2(CH2)2(4-OH-piperidine-1-yl)(S)-2-phenylbutyl
4513,4-dichlorobenzoylHHCH2(CH2)2(4-CO2H-piperidine-1-yl)(S)-2-phenylbutyl
4523,4-dichlorobenzoylHHCH2(CH2)2NH[-(CH2)6-](S)-2-phenylbutyl
4533,4-dichlorobenzoylH HCH2(CH2)2[(S)-2-Me-piperidine-1-yl](S)-2-phenylbutyl
4543,4-dichlorobenzoylHHCH2(CH2)2N(tBu)CH3(S)-2-phenylbutyl
4556-chloro-2-naphtolHHCH21-ethyl-piperidine-4-yl(S)-2-phenylbutyl
4563,4-dichlorobenzylHHCH2(CH2)2(1-piperidinyl)2.2-diphenylether
4576-chloro-2-naphtolHHCH2(CH2)2NHC(=NH)NH2(S)-2-phenylbutyl
4586-chloro-2-naphtol HCH2(CH2)2NHC(=NH)NHMe(S)-2-phenylbutyl

Connection.R1XR2R3YZN(R4a)(R4b)W
4593,4-dichlorobenzoylNHCH2(CH2)2NH2(R)-2-isopropylbenzyl
4603,4-dichlorobenzoylNHCH2(CH2)2NH2(S)-2-isopropylbenzyl
4613,4-dichlorobenzoylHHCH2(CH2)2(1-piperidinyl)(R)-2-isopropylbenzyl
462 3,4-dichlorobenzoylHHCH2(CH2)2(1-piperidinyl)(S)-2-isopropylbenzyl
4636-chloro-2-naphtolHHCH2CH2C(Me2)NH2(S)-2-phenylbutyl
4643,4-dichlorobenzoylHHCH2(CH2)2NH2(S)-2-phenylbutyl
4653,4-dichlorobenzoylHHCH2(CH2)2NHCH(CH3)2(S)-2-phenylbutyl
4666-chloro-2-naphtolHHCH2(CH2)2NH23,5-dichlorobenzyl
4676-chloro-2-naphtolHHCH2(CH2)2(1-piperidinyl)3,5-dichlorobenzyl
4686-chloro-2-naphtolHHCH2CH2C(Me2)(1-piperidinyl)(S)-2-phenylbutyl
4696-chloro-2-naphtolHHCH2(CH2)2NH2(R)-2-isopropylbenzyl
4706-chloro-2-naphtolHHCH2(CH2)2NH2(S)-2-isopropylbenzyl
4716-chloro-2-naphtolHHCH2(CH2)2(1-piperidinyl)(R)-2-isoprop lputil
4726-chloro-2-naphtolHHCH2(CH2)2(1-piperidinyl)(S)-2-isopropylbenzyl
4736-carboxy-2-naphtolHHCH2(CH2)2(1-piperidinyl)2.2-diphenylether
4746-chloro-2-naphtolHHCH2(CH2)2NHC(=NH)NH-CH(CH3)2(S)-2-phenylbutyl
4753,4-dichlorobenzoylHHCH2(CH2)2NH22-ethyl-3-methyl-but-3-enyl
4763,4-dichlorobenzoylHHCH2(CH2) (1-piperidinyl)2-ethyl-3-methyl-but-3-enyl

td align="center"> H
Connection.R1XR2R3YZN(R4a)(R4b)W
4776-chloro-2-naphtolNHCH2(CH2)2NH22-ethyl-3-methyl-but-3-enyl
4786-chloro-2-naphtolNHCH2(CH2)2(1-piperidinyl)(R)-2-ethyl-3-methyl-but-3-enyl
4796-chloro-2-naphtolHHCH2(CH2)2(1-piperidinyl)(S)-2-ethyl-3-methyl-but-3-enyl
4804-biphenylcarboxylicHCH2(CH2)3NHC(=NH)NH2cyclohexylmethyl
481indole-3-acetylHHCH2(CH2)3NHC(=NH)NH2cyclohexylmethyl
4823-chinainternationalHHCH2(CH2)3NHC(=NH)NH2cyclohexylmethyl
4833,4-dichlorobenzoylHHCH2(CH2)2(4,4-debtor-1-piperidinyl)(S)-2-phenylbutyl
4843,4-dichlorobenzoylHHCH2(CH2)2(3,3-debtor-1-piperidinyl)(S)-2-phenylbutyl
485 HHCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
4863,4-dichlorobenzoylHHCH2(CH2)2(1-piperidinyl)2-cyclopropylmethyl
4876-chloro-2-naphtolHHCH2(CH2)2NH22-cyclopropylmethyl
4886-chloro-2-naphtolHHCH2(CH2)2(1-piperidinyl)2-cyclopropylmethyl
4893,4-dichlorobenzoylHHCH2(CH2)2N[-CO(CH2)2CO-](S)-2-phenylbutyl
6-chloro-2-naphtolHHCH2(CH2)3NHCONH2(S)-2-phenylbutyl
4913,4-dichlorobenzoylHHCH2(CH2)2NHCH(Me)CF3(S)-2-phenylbutyl
4923,4-dichlorobenzoylHHCH2CH2CH2N[-COC(Me)2CH2CO-](S)-2-phenylbutyl

td align="center"> (CH2)2(1-piperidinyl)
Connection.R1XR2R3YZN(R4a)(R4b)W
4936-chloro-2-naphtolNHCH2(CH2)2N[-(CH2) 6-](S)-2-phenylbutyl
4946-chloro-2-naphtolNHCH2(CH2)2NHCONHiPr(S)-2-phenylbutyl
4954-biphenylcarboxylicHHCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
4962-phenylthiazol-4-carbonylHHCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
4974-chloro-biphenyl-2-carbonylHHCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
4986-chloro-2-naphtolHHCH2 (CH2)2N(Ac)iPr(S)-2-phenylbutyl
4996-chloro-2-naphtolHHCH2CH2NHiPr(S)-2-phenylbutyl
5006-chloro-2-naphtolHHCH2CH2NC(=NH)NH2(S)-2-phenylbutyl
5102,4-dichlorophenylethylHHCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
5023,4-dichlorobenzoylHHCH2(CH2)2NH22,4-dichlorobenzyl
5033,4-dichlorobenzoylHHCH22,4-dichlorobenzyl
5043,4-dichlorobenzoylHHCH2(CH2)2NHSO2Me2,4-dichlorobenzyl
5053,4-dichlorobenzoylHHCH2(CH2)2NHSO2(4-Me-Ph)2,4-dichlorobenzyl
5063,4-dichlorobenzoylHHCH2(S)-(CH2)2NHCO-CH(iPr)NH22,4-dichlorobenzyl
5076-chloro-2-naphtolHHCH2(CH2)2NH22,4-dichlorobenzyl
5086-chloro-2-naphtolHH CH2(CH2)2(1-piperidinyl)2,4-dichlorobenzyl
5096-chloro-2-naphtolHHCH2(CH2)2NH22-(3-thienyl)butyl
5106-chloro-2-naphtolHHCH2(CH2)2(1-piperidinyl)(R)-2-(3-thienyl)butyl
5116-chloro-2-naphtolHHCH2(CH2)2(1-piperidinyl)(S)-2-(3-thienyl)butyl
5126-chloro-2-naphtolHHCH2(CH2)2NH22-ethyl-2-methylbutyl

Connection.R1 XR2R3YZN(R4a)(R4b)W
5136-chloro-2-naphtolNNCH2(CH2)2(1-piperidinyl)2-ethyl-2-methylbutyl
5146-chloro-2-naphtolNNCH2(CH2)2(4-morpholinyl)2.2-diphenylether
5156-chloro-2-naphtolNNCH2(CH2)2(4-morpholinyl)(S)-2-phenylbutyl
5166-chloro-2-naphtolNNCH2(CH2)2(4-morpholinyl)3,5-dichlorobenzyl
517 3,4-dichlorobenzoylNNCH2(CH2)2(4-morpholinyl)3,5-dichlorobenzyl
518(4-chloro-benzyl)NHCONNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
5193,4-dichlorobenzyl + MeCOAUNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
5203,4-dichlorobenzoylNNCH2(CH2)2NH22-ethyl-2-methylbutyl
5213,4-dichlorobenzoylNNCH2(CH2)2(1-piperidinyl)2-ethyl-2-methylbutyl
5226-chloro-2-naphtolNNCH2(CH2)2(1-piperidinyl)2,3,5-trichlorobenzoyl
5236-chloro-2-naphtolNNCH2(CH2)2NHSO2iPr(S)-2-phenylbutyl
5246-chloro-2-naphtolNNCH2(CH2)2NHCO2nBu(S)-2-phenylbutyl
5256-chloro-2-naphtolNNCH21-iPr-4-piperidinyl(S)-2-phenylbutyl
5266-chloro-2-naphtolNNCH2(CH2)2(1-piperidinyl)R)-2-phenylbutyl
5275-(4-chlorophenyl)-isoxazol-3-carbonylNNCH2(CH2)2(1-piperidinyl)3,5-dichlorobenzyl
5282,4-dichlorobenzoylNNCH2(CH2)2(1-piperidinyl)3,5-dichlorobenzyl
5296-methoxy-2-naphtolNNCH2(CH2)2(1-piperidinyl)3,5-dichlorobenzyl
5306-chloro-2-naphtolNNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
5311-methoxy-2-naphtolNNCH2(CH2 )2(1-piperidinyl)3,5-dichlorobenzyl

Connection.R1XR2R3YZN(R4a)(R4b)W
5324-(trifter-methoxy)cynnamoylNNCH2(CH2)2(1-piperidinyl)3,5-dichlorobenzyl
5335-(4-chlorophenyl)-isoxazol-3-carbonylNNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
5342,4-dichlorobenzoylNNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
5354,5-dichlorophenol R1NCH2(CH2)2(1-piperidinyl)3,5-dichlorobenzyl
5363-fluoro-4-(trifter-methoxy)cynnamoylNNCH2(CH2)2(1-piperidinyl)3,5-dichlorobenzyl
5376-methoxy-2-naphtolNNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
5381-methoxy-2-naphtolNNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
5393-fluoro-4-(trifter-methoxy)cynnamoylNNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl
5406-chloro-2-naphtolNNCH2(CH2)2(1-piperidinyl)(S)-2-phenylbutyl

Table 2:
The synthesis of compounds
Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
14Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-HEScheme 3removing the protective group P3
25Scheme 1Boc-Gly-OHCbz-L-Asp[(NMe)OMe-HEScheme 4restore to aldehyde then reductive amination

Connection.The path And Scheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
31Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
33Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
37Scheme 1Cbz-Gty-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
38Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
38Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3 removing the protective group P3, then dialkylamino alkylamino
39Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
49Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
50Scheme 1Alloc-Gly-OHBoc-L-
Arg(Fmoc)2-OH
Scheme 4removing the protective group P3
54Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
60Scheme 1Cbz-SarFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3

Connection. The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO3HThe conversion And productmodification U
62Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3remove P1 protective group, R1 to allievate, ring metilirovanie, remove P3 protective group
63Scheme 2Boc-Gly-OHH-L-Orn(Cbz)-OllilScheme 4removing the protective group P3
63Scheme 12-naphthoic-G)y-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
64Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
65Scheme 12-naphthoic-Gly-OH Fmoc-L-Om(Boc)-OHScheme 3removing the protective group P3, reductive alkylation
67Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3, guanylurea
79Scheme 1Alloc-β-(2-naphthyl)-L-AlaBoc-L-Arg-(Cbz)2-OHScheme 4removing the protective group P3
81Scheme 1Alloc-β-(2-naphthyl)-L-AlaBoc-L-Arg-(Cbz)2-OHScheme 4removing the protective group P3
83Scheme 1Alloc-β-(2-naphthyl)-L-AlaBoc-L-Arg-(Cbz)2-OHScheme 4removing the protective group P3
85Scheme 1Altoc-β-(2-naphthyl)-L-AlaBoc-L-Arg-(Cbz)2-OHScheme 4removing the protective the group R3
86Scheme 1Alloc-β-(2-naphthyl)-L-AlaBoc-L-Arg-(Cbz)2-OHScheme 4removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
87Scheme 1Alloc-β-(2-naphthyl)-L-AlaBoc-L-Arg-(Cbz)2-OHScheme 4removing the protective group P3
105Scheme 2Boc-Gly-OHH-L-Om(Cbz)-OllilScheme 5removing the protective group P3, guanidinylation, removing the protective groups
105Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
105Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
105Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
106Scheme 2Boc-Gly-OHH-L-Orn(Cbz)-OllilScheme 4removing the protective group P3
107Scheme 2Boc-Gly-OHH-L-Orn(Cbz)-OllilScheme 4removing the protective group P3
108Scheme 2Boc-Gly-OHH-L-Orn(Cbz)-OllilScheme 5removing the protective group P3, guanidinylation, removing the protective groups
109Scheme 2Boc-Gly-OHH-L-Orn(Cbz)-OllilScheme 5 removing the protective group P3, guanidinylation, removing the protective groups
110Scheme 2Boc-Gly-OHH-L-Orn(Cbz)-OllilScheme 5removing the protective group P3, guanidinylation, removing the protective groups

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
111Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
112Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
113Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4 removing the protective group P3
114Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
115Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
116Scheme 2Boc-Gty-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
117Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
118Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
119Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHthe Hema 4 removing the protective group P3
120Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
121Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
122Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
123Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
124Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
125Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4 removing the protective group P3
126Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
127Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
128Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
129Scheme 2Boc-Gly-OHBoc-L-Lys(Cbz)-OHScheme 4removing the protective group P3
130Scheme 2Boc-Gly-OH H-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
131Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
132Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
133Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
134Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
135Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
16 Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
137Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
138Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
139Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
140Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
141Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4 removing the protective group P3
142Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
143Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
144Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
145Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
146 Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
147Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
148Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
149Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
150Scheme 2Boc-Gly-OHH-L-Arg(Cbz)2-OllilScheme 4removing the protective group P3
151Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective gr is PI P3
152Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
153Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
154Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
155Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
156Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
157Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4 removing the protective group P3
158Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3

td align="left"> Scheme 1
Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2NThe conversion And productmodification U
159Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
160Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
161Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
162Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
163Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
164Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
165Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
166Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
167Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
168Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
169Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
170Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
171Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
172Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
173Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4 removing the protective group P3
174Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
175Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
176Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
177Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
178With the EMA 1 Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
179Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
180Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
181Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
182Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
183Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
184Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
185Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
186Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
187Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
188Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
189Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removed the e protective group P3
190Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3

removing the protective group P3
Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
191Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
192Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
193Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
194Scheme 1 Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
195Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
196Scheme 12-naphthoic-Gly-OHFmoc-α-(1-Boc-4-piperidinyl)-DL-Gly-OHScheme 3removing the protective group P3
197Scheme 12-naphthoic-Gly-OHFmoc-α-(1-Boc-4-piperidinyl)-DL-Gly-OHScheme 3removing the protective group P3
198Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
199Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
200Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
201Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
202Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
203Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
204Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
205Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
206Scheme 12-naphthoic-Gty-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
207Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
208Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
209Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
210With the EMA 1 Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
211Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
212Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
213Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
214Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
215Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(NMe)2Pbf-OHScheme 3removing the protective group P3
21 Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
217Scheme 1Alloc-Gly-OHBoc-L-Arg(Fmoc)2-OHScheme 4removing the protective group P3
218Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
219Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
220Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
221Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U222Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3223Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3224Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3, guanidinylation225Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3, reductive alkylation226Scheme 12-naphthoic-Gly-OH Fmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3227Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3228Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3, reductive alkylation229Scheme 12-naphthoic-Gly-OHFmoc-L-Lys(i-Pr)Fmoc-OHScheme 3removing the protective group P3230Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3231Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3232Scheme 1 Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3233Scheme 1Cbz-Giy-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3234Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
235Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
236Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective groups of the P3
237Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
238Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
239Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
240Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
241Scheme 1Cbz-Gly-OHFmoc-L-Om(Boc)-OHScheme 4removing the protective group P3
242Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective groups of the P3
243Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
244Scheme 12-naphthoic-Gty-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
245Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3, reductive alkylation
246Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3, reductive alkylation
247Scheme 12-naphthoic-Gly-OHFmoc-L-Orn (Boc)-OHScheme 3removing the protective group P3, reductive alkylation

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
248Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3, reductive alkylation
249Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
250Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
251Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
252Scheme 1 Cbz-Gty-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
253Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
254Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
255Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4remove P1 protective group, R1 to allievate, calculateresult, remove P3 protective group
256Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3
257Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the safety group P3
258Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino

td align="left"> 260
Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
259Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
259Scheme 1Boc-Gly-OHFmoc-L-Orn(Cbz)-OHScheme 5removing the protective group P3, dialkylamino
260Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3
Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
261Scheme 12-naphthoic-Gly-OHFmoc-L-Orn (Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
262Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
263Scheme 12-naphthoic-G)y-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
264Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
265Scheme 12-naphthoic-Gly-OHFmc-L-Arg(Pbf)-OH Scheme 3removing the protective group P3
266Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
267Scheme 1Cbz-Gly-OHFmoc-L-Orn (Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
268Scheme 1Cbz-Gty-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
269Scheme 12-naphthoic-Gty-OHFmoc-L-ArgPbf)-OH Scheme 3removing the protective group P3
270Scheme 12-naphthoic-Gty-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
271Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3
272Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3
273Scheme 1Cbz-Gly-OHBoc-L-Dab(Fmoc)-OHScheme 4removing the protective group P3
273Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
274Scheme 1Cbz-Gly-OHBoc-L-Dab(Fmc)-OH Scheme 4removing the protective group P3
274Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
275Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
276Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
276Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2H The conversion And productmodification U
277Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
278Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
279Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
280Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
281Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
282Scheme 1Cbz-Gly-OH Fmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
283Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
284Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
285Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
286Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
287Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHSchemes is 3 removing the protective group P3

Scheme 1
Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
288Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
289Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
290Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
291Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
2922-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
293Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3, then the acylation
294Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group P3, then the acylation
295Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
296Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
297Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protection is based groups P3
298Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
299Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then the acylation
300Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then the acylation
301Scheme 1Cbz-β-AlaFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
302Rhythm is a 1 Cbz-β-AlaFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
303Scheme 1Cbz-β-AlaFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
304Scheme 1Cbz-β-AlaFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
305Scheme 1Cbz-β-AlaFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
306Scheme 1Cbz-β-AlaFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
307Scheme 12-naphthoic-Gly-OH Fmoc-L-Arg(Pbf)-OHScheme 3removing the protective group R5 and the amidation, then removing the protective group P3
308Scheme 1Attoc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
309Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
310Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
311Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group P3
312Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective grupper

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
313Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
314Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
315Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
316Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
317Scheme 1 2-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
318Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
319Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
320Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
321Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
322Scheme 12-naphthoic-Gly-OHFmoc-L-Om(Boc)-OHScheme 3removing the protective group P3
323 Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
324Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
325Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
326Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
327Scheme 1Alloc-Gly-OH Fmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
328Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
329Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
330Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
331Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
331Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, ZAT is dialkylamino alkylamino
332Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
333Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
334Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
335Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
336 Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
337Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
338Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
339Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
340Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
341Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3 removing the protective group P3
342Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
343Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group R5 and the amidation, then removing the protective group P3
344Scheme 12-naphthoic-Gly-OHFmoc-L-Arg(Pbf)-OHScheme 3removing the protective group R5 and the amidation, then removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
345Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OH Scheme 4removing the protective group P3, alkylation
346Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3, dialkylamino
347Scheme 1Alloc-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3
348Scheme 1AHoc-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3
349Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
350Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
350Scheme 1 Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
351Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
352Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
353Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
354Scheme 1Alloc-Gly-OHFmoc-L-Dap(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2H P2NH-CH(U)-CO2HThe conversion And productmodification U
355Scheme 1ll-Gly-OHFmoc-L-Dap(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
356Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
357Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
358Scheme 12-naphthoic-Gly-OHCbz-L-Asp[N(Me)OMe]-OHScheme 3the transformation of P3 in the aldehyde then reductive amination
359Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 4removing the protective group is P3, then dialkylamino alkylamino
360Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
361Scheme 1Boc-Gly-OHCbz-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
362Scheme 1Boc-Gly-OHCbz-L-Asp[N(Me)(OMe)]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
363Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe transformation of the AB product modification U
364Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
365Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
366Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
367Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
368Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
369Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
370Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
371Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
372Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
373Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO HP2NH-CH(U)-CO2HThe conversion And productmodification U
374Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
375Scheme 1Cbz-Giy-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
376Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
377Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
378Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
379Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
380Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
381Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, alkylation
382Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, alkylation
383Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, alkylation
384Scheme 12-naphtha is first-Gly-OH Fmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
385Scheme 12-naphthoic-Gly-HEFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
386Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
387Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, alkylation
388Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OH Scheme 3removing the protective group P3
389Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3
390Scheme 12-naphthoic-Gly-OHFmoc-L-Orn(Boc)-OHScheme 3removing the protective group P3
391Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
392Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
393Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3, acylation
394Scheme 1 2-naphthoic-Gly-OHFmoc-L-Dap(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
395Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
396Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
397Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
398Scheme 1 Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
399Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
400Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
401Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
402Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3, acylation
403Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, the ATEM dialkylamino alkylamino
404Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, condensation
405Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, condensation, recovering

/tr>
Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
406Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
407Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
408Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
409Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
410Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
411Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
412Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
413Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
414Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
415Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
416Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 5removing the protective group P3, then dialkylamino ALCALDIA the home
417Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
418Scheme 1Cbz-Gly-OHFmoc-L-Orn(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
419Scheme 1Boc-AibFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
420Scheme 1Boc-AibFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
421Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3
422Scheme 12-on the fully-Gly-OH Fmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
423Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
424Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
425Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
426Scheme 1 Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
427Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
428Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
429Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
430Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4the transformation of P3 in the aldehyde then reductive amination

Connection. The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
431Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
432Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
433Scheme 12-naphthoic-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
434Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
4351 Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4no
436Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
437Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4no
438Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, reductive alkylation
439Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, reductive alkylation

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2/sub> HThe conversion And productmodification U
440Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, reductive alkylation
441Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3
442Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
443Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
444Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde, then in Starowislna amination
445Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
446Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
4478Scheme 1Cbz-Gly-OHN-Fmoc-1(1-Boc-piperidine-yl)-D,L-Gly-OHScheme 4removing the protective group P3
448Scheme 1Cbz-Gly-OHN-Fmoc-1(1-Boc-piperidine-yl)-D,L-Gly-OHScheme 4removing the protective group P3, reductive alkylation

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And product modification U
449Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
450Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
451Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
452Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
453Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive minervan is e
454Scheme 1Cbz-Gly-OHFmoc-L-Asp[N(Me)OMe]-OHScheme 4the transformation of P3 in the aldehyde then reductive amination
455Scheme 1Cbz-GlyN-Fmoc-1(1-Boc-piperidine-4-yl)-D,L-Gly-OHScheme 4removing the protective group P3, reductive alkylation
456Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, alkylation

Connection.The path AndScheme 1: VN(R2)-Y-C02HP2NH-CH(U)-CO2HThe conversion And productmodification U
457Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, alkylation
458Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, alkylation
459Scheme 1Boc-Gly-OHCbz-DL-y-nitro-Leu-OHScheme 4restore P3 in Amin
460Scheme 1Boc-Gly-OHCbz-DL-y-nitro-Leu-OHScheme 4removing the protective group P3 in Amin
461Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
462Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
463Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective the group P3, dialkylamino alkylamino
464Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
465Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then reductive alkylation
466Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
467Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino
468Scheme 1Boc-Gly-OHCbz-DL-γ-nitro-Leu-OHScheme 4restore P3 in Amin, then dialkylamino alkylamino

With the D. The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
469Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
470Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
471Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, dialkylamino alkylamino
472Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, dialkylamino alkylamino
473Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OH Scheme 5removing the protective group P3, alkylation
474Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, alkylation
475Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
476Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, dialkylamino alkylamino
477Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
478Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
479Scheme 1Cbz-GlyFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, dialkylamino alkylamino
480Scheme 2Boc-Gly-OHBoc-L-Arg(Cbz)2-OHScheme 4removing the protective group P3
481Scheme 2Boc-Gly-OHBoc-L-Arg(Cbz)2-OHScheme 4removing the protective group P3
482Scheme 2Boc-Gly-OHBoc-L-Arg(Cbz)2-OHScheme 4removing the protective group P3
483Scheme 1Boc-Gly-OHCbz-L-Asp[N(Me)OMe] Scheme 4the transformation of P3 in the aldehyde then reductive amination
484Scheme 1Boc-Gly-OHCbz-L-Asp[N(Me)OMe]Scheme 4the transformation of P3 in the aldehyde then reductive amination
485Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5; reductive alkylation for R1Xremoving the protective group P3, then dialkylamino alkylamino
486Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
487Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3

P2NH-CH(U)-CO2H
Connection.The path AndScheme 1: VN(R2)-Y-CO2HThe conversion And productmodification U
488Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
489Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)Scheme 4removing the protective group P3, diallylamine anhydride
490Scheme 1Cbz-Gly-OHBoc-L-citrulline-OHScheme 4no
491Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)Scheme 4removing the protective group P3, reductive alkylation
492Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)Scheme 4removing the protective group P3, diallylamine anhydride
493Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)Scheme 4removing the protective group P3, then dialkylamino alkylamino
494Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)Scheme 4removing the protective group P3, then acylation with isocyanate
495Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP2NH-CH(U)-CO2HThe conversion And productmodification U
496Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dealkylase the s-alkylamino
497Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
498Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then reductive alkylation, satemization
499Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3, then reductive alkylation
500Scheme 1Cbz-Gly-OHFmoc-L-Dap(Boc)-OHScheme 4removing the protective group P3, then guanylurea
510Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, guanidinylation s,removing the protective groups
502Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
503Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-C02HP2NH-CH(U)-CO2HThe conversion And productmodification U
504Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then sulfonylureas s
505Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then sulfonylureas s
506 Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, acylation, removing the protective groups
507Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
508Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
509Scheme 1N-(6-CL-2-naphthoic)-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3
510Scheme 1N-(6-Cl-2-naphthoic)-Gly-OHFmoc-L-Dab(Boc)-OHScheme 3removing the protective group P3, then dialkylamino alkylamino
511Scheme 1N-(6-Cl-2-naphthoic)-Gly-OHFmo-L-Dab(Boc)-OH Scheme 3removing the protective group P3, then dialkylamino alkylamino
512Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3

Connection.The path AndScheme 1: VN(R2)-Y-C02HP2NH-CH(U)-CO2HThe conversion And productmodification U
513Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
514Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
515Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OH Scheme 4removing the protective group P3, then dialkylamino alkylamino
516Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
517Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
518Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5,primeneniia for R1Xremoving the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
519Scheme 1 Fmoc-L-Dab(Boc)-OHScheme 5; reductive alkylation, then acetylation for R1X and R2removing the protective group P3, then dialkylamino alkylamino
520Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3
521Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
522Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
523Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then sulfonylamine
524Scheme 1Cbz-Gly-OH Fmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then acylation with CHLOROFORMATES

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
525Scheme 1Cbz-Gly-OHFmoc-DL-2-(1-Boc-4-piperidyl)-Gly-OHScheme 4removing the protective group P3, then reductive alkylation of the ketone
526Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
527Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
528Schema Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
529Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
530Scheme 1Cbz-[15N,1,2-13C2]Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then reductive alkylation, then acetylation
531Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And product modification U
532Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
533Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
534Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
535Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
536Scheme 1Alloc-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkyldiphenyl/td>
537Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
538Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino
539Scheme 1Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 5removing the protective group P3, then dialkylamino alkylamino

Scheme 4
Connection.The path AndScheme 1: VN(R2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
540Scheme 1 with the exchange of D2O when removing seditious Fmoc group and restore NaBD3CNCbz-Giy-OHFmoc-L-Dab(Boc)-OHremoving the protective group P3, then reductive alkylation, then acetylation
541Scheme 1Cbz-Gly-OHFmoc-D-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
542Scheme 2Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
543Scheme 2Cbz-Gly-OHFmoc-D-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
544Scheme 2Cbz-Gly-OHFmoc-L-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino

Connection.The path AndScheme : VN(R 2)-Y-CO2HP1NH-CH(U)-CO2HThe conversion And productmodification U
545Scheme 2Cbz-Gly-OHFmoc-D-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino
546Scheme 1Cbz-Gly-OHFmoc-D-Dab(Boc)-OHScheme 4removing the protective group P3, then dialkylamino alkylamino

Example 102 - test radioligand binding human MC5R

Assessment of binding of compounds to human MC5R (hMC5R) by moving125I-labeled NDP-MSH receptor ligand peptide was carried out mainly as described in the specifications manufactured by Perkin Etmer to accompany them frozen hMC5R membranes (Perkin Elmer catalog number RBXMC5M400UA).

[125I] NDP-MSH: labeled radioactive label self-production and purified by HPLC:

Na125I (0.5 MCI, to 17.4 CI/mg) was added to 50 μl of sodium phosphate (50 mm, rn,4) in an Eppendorf tube, pre-coated with IODOGEN. After incubation for 10 m the chickpeas phosphate buffer, containing iodine added to NDP-MSH (10 μl of 1 mg/ml) in a separate Eppendorf tube. It was incubated for a further 10 minutes

Iodized NDP-MSH was purified by HPLC on Bond SB 300 column, using solvent A: 0.05% of TFA and solvent B: 90% acetonitrile of 0.045% TFA with a linear gradient, 0-67% within 60 minutes.125I NDP-MSH was elyuirovaniya 52 minutes after its source material (48 minutes) and was calculated and stored in the freezer. It was used not later than 48 hours as radioactive decay and decomposition of the ligand, which led to significantly reduced the specific binding observed after 72 hours.

Reagents:

Incubation buffer: 25 mm ARE(N2-hydroxyethylpiperazine-N2-25 econsultancy acid)-KOH (pH 7.0), 1.5 mm NAC)2, 1 mm MgSO4, 0.1 M NaCl, 1 mm 1,10 - phenanthroline and 1 tablet proteasome inhibitor Complete™/100 ml (Roche, catalog number 1873580).

Frozen membrane hMC5 Perkin Eimer: catalog number RBXMC5M400UA, 0.4 ml/vial; 400 microspine/vial, 0,78 mg/ml protein concentration

Tubes of frozen membranes were rapidly thawed immediately before use, diluted in binding buffer and shook. Kept resuspendable membrane on ice until then, until they were added to the wells.

Protocol binding for 400 microspine on the tube:

Test OS is Westlake 96 hole polypropylene tablets. Membrane (0.78 µg, 40 μl of 1:40 dilution in incubation buffer) was added to a [125I] NDP-MSH (0,84 nm; 2200 CI/mmol) and test compounds in a total volume of 140 μl. They were incubated for 1 hour at 37°C. Nonspecific binding was determined using a 3 mm NDP-MSH. The tablet was filtered using a Tomtec harvester cells with GF/A filters (Wallac) (pre-soaked in 0.6% of polyethylenimine) and washed three times with 1.0 ml of ice promising buffer (above the incubation buffer without 1,10 - phenanthroline and tablets proteasome inhibitor Compiete™). The filters were dried in a 37°C oven, put in a bag for samples and added 5 ml Betaptatescint (Wallac). The resulting filters were counted in magazines in Microbeta Tritux (Wallac) for 1 min, and Nonspecific binding only at 5%. Data analysis was performed using GraphPad Prism 4 using competitive binding with single-site model and the constant coefficient of the hill. Used the following equation: Y = Bottom value + (the Upper value - Lower value)/1/10(X-logEC50), where X = log(concentration) and Y = linking for compliance with the data.

Example 103 - Identification of preferred diastereoisomer to associate with MC5R

Four diastereoisomer one set deputies were tested for binding in the test hMC5R, as in Examples 102, as shown in Table 3.

Table 3:
Activity four diastereomers
Connection.stereochemistryHuman MC5R IC50(Nm)
102(3R,RS)3500

103(3R,5R)500
104(3S,5R)1500
105(3S,5S)56

As you can see 3S, 5S isomer is almost ten times more than the next most active isomer and significantly more active than the other two possible isomers. This unexpected high level differential activity and, therefore, specificity (S,S) diastereoisomer was unexpected and not predictable from knowledge hMC5R or previously known ligands.

Example 104 - Activity of selected compounds: binding hMC5R

Typical compounds of this invention were tested for binding in the test hMC5R as in Example 102, with results as listed in Table 4. Compounds were protest is arranged as their triptorelin or cleaners containing hydrochloride salt, or as the free base.

Table 4:
Properties of compounds x=<10 μm; xx=<1 μm, xxx=<100 nm, xxxx=<10 nm
Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
14556,25,74XXX
25595,36,22XXX
31to 539.3of 5.92XX
33599,4of 6.31XXXX
37473,45,59XXX
38to 541.35,78XXX
39to 541.35,67XXX
49 499,35,77XX
50613,5of 5.89X
54425,75,27XX
60629,46,27X
62629,36,22XX
63535,35,76XX
64603,36,04XXX
65577,25,97XXX
67591,35,94XXXX
71549,3to 5.93XX
79606,4UAH 6,033X
81743,45,489XX
83650,36,524XX
85606,26,008X
86743,55,410XX

Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
87650,46,424X
105577,35,79XXX
106561,46,05XX
107524,35,63XX
108603,36,11XXX
566,2the 5.65XX
110591,2of 5.82XX
111581,35,95XXX
112578,35,26XXX
113579,35,52XX
114578,35,72XX
115527,35,41XX
116578,35,78XX
117509,25,51XX
118523,35,56X
119523,25,51 X
120512,35,10X
121549,45,96XX
122509,25,56XX
123of 523.45,63X
124509,25,41X
125523,3of 5.68X
126549,35,79XX
127554,2by 5.87X
128554,2by 5.87XX
129539,15,58X
130596,5 by 5.87X
131582,45,88X
132567,45,62X
133567,45,62X
134582,45,88XX
135583,45,86XX
136595,45,31XXX
137595,4by 5.87XX
138527,25,33XX
139533,35,54X
140620,26,16XXX
141 620,26,21XX
142566,35,70XXX
143555,25,55XX
144555,25,74XXX
145583,46,21XX
146587,24,90X
147547,45,78XX
148571,25,34XX
149567,14,48X

Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
150 568,14,87X
151519,55,23X
152595,4of 5.92XXX
153553,55,58XXX
154595,45,95XX
155609,45,88XX
156607,55,96XXX
157609,4-X
158607,45,88XXX
159621,36,22XXX
160585,66,00X
161557,45,50X
162607,55,94XX
163607,25,69XX
164585,45,64XX
165557,3the 6.06XXX
166559,55,47XXX
167585,55,58XX
168569,55,17XX
169583,65,70XX
170567,65,79XXX
171621,46,01 XX
172571,5the 5.65XXX
173567,55,50XX
174567,5lower than the 5.37XX
175625,5of 5.81XXX
176for 587.4the 5.65XXX
177584,54,84XX
178593,4the ceiling of 5.60XX
179583,65,41XX
180655,25,97XXXX
181501,45,20XX
182570,2 5,64X
183570,25,66XX
184583,55,43XXX
185607,35,28XXX
186583,4lower than the 5.37XXX
187595,65,64XXX
188for 587.45,78XX
189569,55,23XX
190567,7of 5.92XXX
191621,4to 6.19XX
192569,65,23XX
193 571,55,69XXX
194567,55,98XXX
195571,56,00XX

Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
196561,3of 5.84XX
197575,45,98XX
198571,15,69XXX
199621,3to 6.19XXX
200591,26,02XX
201493,35,41XX
202 545,25,91XX
203591,35,88XXX
204591,35,90XX
205479,45,09XX
206609,46,13XX
207589,35,69XXX
208605,35,85XXX
209631,46,09XXXX
210597,4of 5.89XXX
211615,36,20XXX
212511,35,63XX
213545,4of 5.92XXX
214637,66,15XX
215605,55,94XXX
216553,35,88XXX
217592,44,99X
218525,35,79XXX
219529,55,59XXX
220553,5by 5.87XXX
221507,25,64X
222513,5of 5.68XX
223553,3of 5.89 XXX
224549,7by 5.87XX
225617,46,21XXX
226523,35,49X
227575,55,72X
228611,26,20XXXX
229591,46,03XXX
230547,55,70XXX
231to 536.55,47XX
232561,76,11XX
233533,5of 5.53XX
234585,5 6,23XXX
235550,5of 5.81XXX
236568,5the 5.45X
237586,56,18XXX
238542,5to 5.57XX
239568,45,91XX
240579,7the ceiling of 5.60XX
241565,55,42X

td align="center"> 5,58
Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
242506,45,73XX
243519,3 5,78XX
244637,5of 5.84X
245624,36,28XXX
246603,26,14XXX
247589,46,04XXX
248543,36,30XXX
249487,25,13X
250613,5the 6.06XXX
251537,45,66X
252531,6the 5.65XX
253551,55,47XX
254 543.5 nm5,77X
255543.5 nm5,66XX
256581,55,10XX
257591,45,94XXX
258599,45,99XXX
259613,5between 6.08XXX
260521,45,85XX
261589,3of 5.81XXX
262575,55,79XXX
263537,25,61X
264551,45,70X
265558,44,86X
266579,65,73XXX
267581,4of 5.84XXX
268621,26,07XXX
269598,65,27XX
270626,75,64X
271507,36,35XX
272517,46,51XXX
273515,35,18XXX
274511,4of 5.81XXX
275575,3of 6.71 XXX
276585,46,83xxxx
277to 539.3by 5.87XX
278499,55,62XX
279497,65,58XX
280531,4of 5.89XXX
281607,36,29xxxx
282567,35,99XXX
283565,4to 5.93XXX
284583,56,02xxxx
285579,66,18XXX
286515,3XX
287620,55,44XX

Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
288620,55,38X
289531,55,22XX
290559,55,74XX
291607,4the 6.06XX
292557,45,61XX
293567,36,52XX
294635,57,34XX
295593,5 6,02XXX
296RUB 573.45,47XX
297481,45,47XX
298521,56,10XXX
299641,47,38XX
300655,3to 7.59XX
301485,35,17X
302553,3of 5.82XX
303535,35,72XX
304553,55,39X
305621,2the 6.06XX
306 603,45,94XX
307572,34,91X
308519,2to 5.93XX
309511,25,94XXX
310540,35,61XX
311523,2lower than the 5.37XX
312498,45,49XX
313481,55,27X
314514,35,52X
315514,25,42X
316505,45,27X
317480,35,33X
318514,4the 5.65X
319514,45,62XX
320514,35,63X
321477,35,35X
322531,5the 5.65X
323480,45,38X
324487,25,55XX
325527,35,96XX
326587,26,33XXX
327567,36,12 XXX
328577,2of 6.31xxxx
329443,25,43XX
330435,35,46XX
331503,15,58XX
332511,45,73XXX
333493,75,71XXX

Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
334427,35,04X
335423,45,28X
336427,35,13 X
337423,35,32X
338489,46.42 perXX
339589,4of 5.92XX
340581,36,03X
341480,45,33X
342555,4of 5.81XXX
343612,65,49X
344620,5-X
345595,46,12XX
346637,26,30X
347505,1 6,46XX
348485,26,26XX
349491,25,69XX
350573,16,07XX
351565,2to 6.88XXX
352491,25,69XX
353483,45,77XXX
354559,16,12XX
355539,2of 5.84XX
356473,3of 5.29XX
357473,2to 5.21X
358 549,46,03XX
359621,46,13XXX
360493,35,32XX
361587,26,17XXX
362577,46,04XXX
363559,36,01XXX
364of 551.35,99XXX
365551,46,04XXXX
366555,3to 6.19XXX
367575,46,11XXX
368589,3the 6.06XXX
369443,6are 5.36XX
370459,95,66XX
371503,25,74XX
372511,4the 5.65XXX
373527,35,95XXX
374573,26,07XXX
375483,35,97XX
376465,4of 5.81XX
377475,35,98XX
378623,26,41XXXX
379607,46,17 XXXX

Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
380585,46,12XXX
381573,26,12XXX
382563,45,95XX
383581,36,12XX
384479,1of 5.68X
385487,4the 5.45XX
386551,56.42 perXXX
387525,3of 6.31XX
388487,35,69 X
389473,45,51XX
390487,4of 5.40X
391601,3between 6.08XXX
392533,3of 5.82X
393622,36,90X
394555,46,00XX
395555,46,10XXX
396607,56,60XXX
397539,46,32XX
398593,56,26XXX
399525,3 6,03XX
400601,36,09XXX
401533,2of 5.81XX
402627,47,20X
403601,36,10XXX
404609,4of 7.64XX
405613,4of 6.31XXX
406575,36,26xxxx
407537,45,98XXX
408525,15,96XXX
409561,46,26xxxx
410 559,16,11XXX
411545,16,01XXX
412569,3of 5.92XX
413kzt645.36,28XXXX
414640,26,7XXX
415561,4to 6.88XXX
416545,1of 6.68XX
417589,46,24XXX
418573,15,95XXX
419559,15,90XX
420627,46,56XX
421493,2of 5.68X
422493,25,71X
423561,4to 5.93X
424561,46,09XX
425581,36,93XX

Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
426547,36,00XXX
427561,2of 5.92XXX
428567,26,94XX
429581,26,45XXX
430547,26,12XXX
431574,35,67XXX
432555,36,15XXX
433555,36,25XXX
434607,26,20XXX
435539,25,90X
436607,36,11XX
437539,15,94X
438577,16,37XXXX
439561,16,17XXX
440549,26,28 XXXX
441507,26,00XXX
442595,26,50XXXX
443560,35,64XXX
444575,26,62XXX
445575,26,27XXXX
446573,26,28XXXX
447547,25,96XXX
448617,26,52XXX
449for 587.46,55XXX
450575,2of 5.82XXX
4516034 5,98XXX
452573,16,32XXX
453573,16,18XXXX
454561,26,21XXX
455575,2the 6.06XXX
456593,46,01XXX
457549,2by 5.87XXX
458563,36,05XXX
459457,25,64X
460457,25,78X
461525,26,05XXX
462525,36,13XXX
463535,26,33XX
464491,35,63XX
465533,25,94XXX
466533,16,44XXX
467603,36,44XXX
468603,27,15XXX
469473,15,99XX
470473,26,09XX
471541,26,34XXX

Connection. MS (M+1)tR(minutes)MC5R radioligand IC50
472541,1to 6.43XXX
473633,45,66XX
474to $ 591.16,36XXXX
475to 455.25,16X
476523,36,09XX
477471,1of 5.53XXXX
478to 539.36,11XXX
479539,2to 6.19XXXX
480519,35,72XX
481496,34,91 XXX
482494,44,65XX
483595,36,30XXX
484595,36,39XX
485545,25,91XXX
486523,05,88XX
487471,15,79XX
488to 539.36,14XXX
489573,16,50X
490564,56,60XX
491587,26,61XX
492 601,37,03X
493589,36,59XXX
494592,37,08XX
495567,36,34XXX
496574,26,14XXX
497601,36,69XXX
498591,37,24XX
499535,36,94XXX
500535,36,37XXX
510573,16,13XX
502519,25,98XX
587,16,34XX
504597,16,61X
505673,07,50X
506618,4-X
507533,16,20XXX
508603,1to 6.57XXX
509was 513.36,00XXX
510581,26,22XXX
511581,06,33XXXX
512473,36,03XX
513541,16,36 XXX
514625,4to 6.57XXX
515577,26,30XXX
516603,16,45XXX
517589,16,23XXX

Connection.MS (M+1)tR(minutes)MC5R radioligand IC50
518554,36,02XX
519587,16,50X
520457,05,73X
521525,26,20XXX
522637,06,75 XXX
523613,37,03XXX
524607,2-XX
525589,5to 6.19XXX
526574,86,27XXXX
527618,96,74XXX
528587,7to 6.19XXXX
529596,96,20XXX
530578,06,38XXXX
531597,06.42 perXXX
532626,96,70XXXX
533591,9 6,61XXXX
534559,06,03XXXX
535612,8? 7.04 baby mortalityXX
536644,96,79XXX
537570,96,04XXX
538570,86,21XXX
539618,86,61XXXX
540Kostroma 579.96,39XXXX

Example 105 - Test radioligand binding MC5R using MC receptors from other species

Radioligand binding and testing camp was also performed using 5 membranes and cells expressing MC5R cloned from other species (mouse MC5R membrane obtained from Euroscreen; MS receptors dog, macaque-rhesus, cynomolgus monkey and Guinea pigs have been cloned is expressed from cDNA libraries and temporarily transliterowany, as described in Examples 107 and 109. The plasma membrane of the cells tested in radioligand test as 10 Example 102.

Example 106 - Activity of selected compounds: MC5R other types

Typical compounds of this invention were tested for binding to MC5R from other species, as described in Example 105, the 15 results are listed in Table 5.

Table 5:
The binding of selected compounds with MC5R of different types

Connection.human MC5R (membrane) IC50(nm)human MC5R (whole cells) IC50(nm)mouse MC5R (membrane) IC50(nm)canine MC5R (whole cells) IC50(nm)macaque-rhesus MC5R (membrane) IC50(nm)macaque-rhesus MC5R (whole cells) IC50(nm)
105572194000640060273000
64 30127-130007307>5000

These results demonstrate the selectivity of the compounds of this invention for human MC5R compared to MC5R in other species. Although there is activity in other species, it is significantly reduced compared to human MC5R, which would not be expected, considering the high receptor homology between species.

Example 107 - Test radioligand binding MC1R, MC3R and MC4R person

Tests radioligand binding was performed using commercial or prepared in-house design hMC1R, hMC3R and hMC4R membranes and [125I] NDP-MSH, according hMC5R the method in Example 102.

The plasma membrane of its own design prepared from transfected mammalian cells (prepared as in Example 109, using plasmid DNA containing the human MC1R, MC3R or MC4R gene or another gene of interest in a plasmid vector with the replication origin of mammal):

Attached to the substrate, the cells were washed with warm buffer saline Khanka (HBSS). 1 ml of cold HBSS was added to each vessel and the cells were describle rubber scraper. Of erased cells were added in 50 ml samples of the CGS on ice. The tablets were then rinsed twice with 5 ml cold HBSS, and it is also added to the test tube. The cells were centrifuged at 1000×g for 5 minutes in a bench top centrifuge and the supernatant decantation. The remaining cellular precipitate resuspendable in 0.25 M sucrose. The cell suspension was again centrifuged as before and the precipitate resuspendable in 5 ml of 0.25 M sucrose containing protease inhibitors. Cells are homogenized by 10 seconds ripple Ika a dispersant, followed 30 seconds on ice. Homogenization and ice incubation was repeated three times. The mixture was then centrifuged at 1260×g for 5 minutes the Supernatant decantation in another centrifuge tube, to which was added a buffer containing 50 mm Tris (Tris(hydroxymethyl)aminomethane), pH 7.4, 12.5 mm MgCl2, 5 mm EGTA (etilenvinilatsetata acid) and protease inhibitors to a final volume of 30 ml was centrifuged at 30,000×g for 90 min at 4°C. the Resulting precipitate resuspendable in 1 ml of the above buffer, which also contained 10% glycerol. Took aliquots of membranes in cryoprobes, which were quickly frozen in a bath of dry ice/ethanol before storage at -80°C until until required for use.

Example 108 subtype Selectivity melanocortin receptor selected connections: linking hMCR

Typical is haunted compounds of this invention were tested for binding in the test DMC1R, hMC3R, hMC4R and hMC5R, as in Examples 103 and 108, as listed in Table 6.

Table 6:
The selectivity of binding hMCR selected compounds
Connection.human MC5R IC50(nm)human MC1R IC50(nm)human MC3R IC50(nm)human MC4R IC50(nm)
10557666017503280
6431922022403490
339285015006060
33115020000183020000

These results demonstrate the selectivity of the compounds of this invention for human MC5R compared to other receptor subtypes in human chalk is nocarcinoma receptor family.

Example 109 - Inhibition or stimulation of camp signal in cells expressing MC5R person

Transient transfection of cell lines mammals:

The cell line of mammalian cells human embryonic kidney (SOME 293)contained in the modified according to the method of Dulbecco environment Needle (DMEM) with 5% embryonic bovine serum (BSA), L-glutamine, high glucose and antibiotic/antifungal. The day before transfection, cells were Persiani using trypsin/EDTA and seeded in 75 cm2the vessels so that they were approximately 90% confluent the next day. The next day, the cell medium was replaced with fresh antibiotic/antifungal-containing DMEM. Approximately 100 µl transfection lipid Turbofectin 8.0 (Origene Technologies, MD, USA) was diluted in 1.0 ml serum not containing antibiotic/antifungal OptiMEM in a sterile 15 ml tube and incubated for 5 min at room temperature. After incubation, approximately 10-20 μg of plasmid DNA expressing the gene of interest (for example: pCMV6-XL4: Homo sapiens melanocortin 5 receptor (Origene Technologies, MD, USA) diluted in transfection mixture and incubated for another 30 min at room temperature. The solution of DNA/lipid then added drop by drop to the medium covering the cells with a gentle rocking of the vessel. 24 hours after Tran the infection cells were Persiani and sown directly into two 75 cm 2vessels and left for allocation. 48 hours after transfection cells were collected for use in the test solution for cell dissociation.

Test stimulation of cyclic-adenosine monophosphate [camp]:

Cells of SOME 293, temporarily expressing human MC5R, were suspended in a stimulating buffer (buffer solely solution Khanka (HBSS), 0,1% BSA, protease inhibitors and 0.5 mm 3-isobutyl-1-methylxanthines) at 4×106cells/ml 5 ál of cells, plus compounds/peptides, as described below, was added to the wells of 384-well of the tablet, as soon as possible after resuspendable.

For detection of antagonistic activity of the diluted test compounds at varying concentrations in a stimulating buffer in a fourfold concentrate and added to 2.5 μl in the wells containing cells. 2,5 ál four times the desired concentration of NDP-MSH or alpha-MSH was added to all wells containing compounds. The negative control wells contained twice concentrated NDP-MSH or alpha-MSH separately without a connection.

For detection of antagonistic activity, diluted test compounds at varying concentrations in a stimulating buffer in double concentrate and added 5 μl to the wells containing cells. The positive control wells contained only NDP-MSH or alpha-MSH (without connections)in double concentrate

Wells monitoring the basal level (camp) contained only stimulating buffer (without agonist or connections). On the tablet were included known concentration camp (standards) in stimulating the buffer, but the cells in these wells was not added. The tablet is then incubated for 30 minutes at 37°C with mild agitation. After incubation added 10 ál lyse buffer (10% tween-20, 1 M HEPES, 0.1% of BSA (bovine serum albumin), protease inhibitors, ddH2O (double-distilled water)) in all measured wells. Discovery camp then performed using a set of Alphascreen cAMP (Perkin Elmer, USA), as briefly described below. Breeding 10 ál pellet acceptor/ml lyse buffer prepared in low light conditions. 5 µl of the diluted granules acceptor was added to each measured well, the tablet then incubated for 30 min at room temperature, in the dark, with a weak shaking. In low light conditions, granules donor were diluted in 10 ál/ml lyse buffer, to which was added to 0.75 ál of biotinylated camp/ml lyse buffer. This mixture was allowed to incubated for 30 min at room temperature (in the dark) before continuing the test. After incubation, 5 µl/ml of a mixture of biotinylated camp/donor pellet was added per well in low light conditions, and p is unset incubated in the dark at room temperature for an additional hour. Tablets read on a tablet reader Envision (Perkin Elmer) after 1 hour and ~16 hours of incubation. The concentration of camp in the cells was determined using the 'standard curve', formed from the results of known concentrations of camp, as described below.

Each analytical tablet contained a standard curve of known concentrations of camp, in 10-fold dilutions. It is an essential part of the analysis, because there is high inter-tablet variability. Tablets read on megamarketinccom tablet reader Envision equipped Alphascreen technology, and raw data were imported into the software GraphPad Prism 4 (GraphPad, USA) for analysis. Curve adjusted to known concentrations using non-linear regression, in particular using a sigmoidal equation "dose - response" (Y = Lower value + (the Lower the value + (the Upper value - Lower value)/1+10logEC50-X), where the equation shows the response as a function of logarithm of concentration. X represents the logarithm of the concentration of peptide/compound, and Y is the response. Also considered in this equation are the lower plateau, the top plateau of the curve and EC50(effective concentration, 50%)

Example 110 - Activity of selected compounds: hMC5R

Typical compounds of this invention were tested for agonism or antagonism MC5R, as in Example 109, the results are listed in Table 7.

Table 7:
Agonism and antagonism hMC5 selected connections
Connection.human MC5R EC50(camp, agonism) (nm)human MC5R IC50(camp, the antagonism of 10-6M alpha-MSH) (nm)
105>10000400
64>1000070
33>10000190
331>1000094

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Details of certain embodiments described in this invention can not be considered as limitations. A variety of analogs and modification can be made without deviating from the essence and scope of this invention and it is understood that such equivalent embodiments of a part of this invention.

1. The compound of formula (I):
,
where
Y represents a group of formula -(CR9R10)-;
X is selected from the group consisting of-C(=O)-, -OC(=O)-, -NHC(=O)-, -(CR11R12)- and S (- O)2-;
Z represents a group of formula -(CR13R14)q-;
R1selected from the group consisting of C1-C12the alkyl, optionally substituted by one Deputy, selected from naphthyl, indole and biphenyl; C2-C12alkenyl, substituted Deputy selected from tanila, naphthyl and phenyl, with the specified phenyl optionally substituted with 1-2 substituents selected from halogen, triptoreline, C1-C6of alkyl, methoxy and is hydroxy; C3-C6cycloalkyl; C6-C10aryl, optionally substituted with 1-2 substituents selected from halogen, phenyl, amino, phenoxy, C1-C6of alkyl, methoxy, hydroxy and carboxy; and (C4-C9heteroaryl selected from indole, quinoline, cinoxacin, benzofuranyl, benzothiophene, benzimidazole, benzotriazole, benzodioxane, benzothiazole, pyrazole, purile and isoxazol, optionally substituted Deputy selected from C1-C6the alkyl and phenyl;
R2and R3each independently selected from the group consisting of H and C1-C12of alkyl;
R4aselected from the group consisting of H, C1-C12the alkyl, optionally substituted by phenyl; C2-C12alkenyl, C3-C6cycloalkyl, C6aryl, C(=O)R15C(=O)NR15R16C(=O)OR15, SO2R15and-C(=NR15)-NR16R17;
R4drepresents hydrogen or
R4aand R4btaken together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclic fragment selected from piperidine, research, pyrrolidine and azetidine where the Deputy is selected from C1-C6of alkyl, hydroxy, halogen, carboxy, oxo;
each R5aand R5brepresents H, or
R6, R7and R8each independently selected the C group, consisting of H, C1-C12of alkyl, C3-C6cycloalkyl; C6-C10aryl, optionally substituted with halogen, or taken together with the carbon atom to which they are attached, two or more of R6, R7and R8form a fragment selected from the group consisting of C2-C12alkenyl; C3-C6cycloalkyl, optionally substituted C1-C6the alkyl, C6aryl, optionally substituted by 2 substituents selected from halogen;
each R9and R10represents H or C1-C12alkyl, substituted naphthyl;
each R11and R12represents H;
R13and R14represent H, or
each R15, R16and R17independently selected from the group consisting of H, C1-C12of alkyl, C3-C6cycloalkyl; C6aryl substituted by one Deputy, selected from C1-C6of alkyl; and C5-heteroaryl, optionally containing one nitrogen atom, and the specified heteroaryl represents pyridyl;
q is an integer selected from the group consisting of 2, 3 and 4;
r represents 1;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where R1represents a C6-C10aryl, optionally substituted with 1-2 substituents, wybran the mi from halogen, phenyl, amino, phenoxy, C1-C6of alkyl, methoxy, hydroxy, carboxy.

3. The compound according to claim 2, where R1represents a C6-C10aryl selected from the group consisting of phenyl, optionally substituted by 1-2 substituents selected from halogen, phenyl, amino, phenoxy, C1-C6of alkyl, methoxy, hydroxy and carboxy; and naphthyl, optionally substituted by 1-2 substituents selected from halogen, phenyl, amino, phenoxy, C1-C6of alkyl, methoxy, hydroxy and carboxy.

4. The compound according to claim 1, where R1represents a C2-C12alkenyl, substituted phenyl, with the specified phenyl optionally substituted with 1-2 substituents selected from halogen, triptoreline, C1-C6of alkyl, methoxy and hydroxy.

5. The compound according to any one of claims 1 to 4, where q is selected from the group consisting of 2, 3 and 4.

6. The compound according to any one of claims 1 to 4, where q represents 2.

7. The compound according to any one of claims 1 to 4, where q is a 3.

8. The compound according to any one of claims 1 to 4, where q is a 4.

9. The compound according to any one of claims 1 to 4, where R4aselected from the group consisting of H, -C(=NH)NH2-C(=NH)N(CH3)2, -C(=NH)NH, -C(=O)CH3, -C(=O)cyclohexyl, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH(CH3)CH2CHsub> 3, -CH2CH(CH3)2, -C(CH3)3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and phenyl.

10. The compound according to claim 1, where R4aand R4btaken together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclic fragment selected from the group consisting of piperidine-1-yl, pyrrolidin-1-yl, azetidin-1-yl and morpholine-4-yl, and optional Deputy selected from C1-C6of alkyl, hydroxy, halogen, carboxy, oxo.

11. The compound according to any one of claims 1 to 4 or 10, where R7represents H.

12. The compound according to any one of claims 1 to 4 or 10, where R6and R8each independently selected from the group consisting of H, C1-C12the alkyl and C6-C10aryl, optionally substituted with halogen.

13. The compound according to any one of claims 1 to 4 or 10, where R6selected from the group consisting of H, methyl, ethyl, isopropyl, propyl, 2-ethylpropyl, 3,3-dimethylpropyl, butyl, 2-methylbutyl, isobutyl, 3,3-dimethylbutyl, 2-ethylbutyl, penttila, 2-methylpentyl and phenyl, optionally substituted with halogen.

14. The compound according to any one of claims 1 to 4 or 10, where R8selected from the group consisting of H, methyl, ethyl, isopropyl, propyl, 2-ethylpropyl, 3,3-dimethylpropyl, butyl, 2-methylbutyl, isobutyl, 3,3-dimethylbutyl, 2-ethylbutyl, penttila, 2-methylpentyl, hexyl, Atila, Attila and phenyl, optionally substituted with halogen.

15. The compound according to any one of claims 1 to 4 or 10, where R6, R7and R8taken together with the carbon atom to which they are attached, form a phenyl group optionally substituted with two substituents selected from halogen.

16. The connection indicated in paragraph 15, where R6, R7and R8taken together with the carbon atom to which they are attached, form a disubstituted phenyl group.

17. Connection P16, where disubstituted phenyl group represents a 2,4-disubstituted-Hairdryer-1-ilen group or a 3,5-disubstituted-Hairdryer-1-ilen group.

18. Connection item 16 or 17, where disubstituted phenyl group represents a 3,5-dichlorophen-1-ilen group.

19. A compound selected from the group consisting of the following compounds:
- N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(2-(diethylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-6-fluoro-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)m is Teal)-2-naptime
- N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)naphthalene-2-sulfonamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo-N-methyl-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-4-methyl-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-(isopropylamino)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-(3-methylguanine)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-3-butyl-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide
- N-((S)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)ndimethylacetamide
- (S)-2-acetamido-N-((S)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)-3-(1H-imidazol-5-yl)propanamide
- propyl (S)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)etelka is Banat
- N-((R)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)ndimethylacetamide
- (S)-2-acetamido-N-((R)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethyl)-3-(1H-imidazol-4-yl)propanamide
- propyl (R)-1-((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-2-(naphthalene-2-yl)ethylcarbamate
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-biphenyl-4-carboxamid
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-1H-indole-2-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl) - biphenyl-4-carboxamid
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-1H-indole-2-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-(naphthalene-2-yl)ndimethylacetamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-1,2,3,4-tetrahydronaphthalen-2-carboxamid
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)quinoline-3-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)cinoxacin-2-carboxamid
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)isoquinoline-3-carb is camid
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)benzamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)quinoline-2-carboxamide
- N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-(naphthalene-2-yl)ndimethylacetamide
- N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-1-naptime
- N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-(1H-indol-3-yl)ndimethylacetamide
- N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-(biphenyl-4-yl)ndimethylacetamide
- N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-(naphthalene-2-yl)ndimethylacetamide
- N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-1-naptime
- N-(((3S,5S)-3-(4-aminobutyl)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-(naphthalene-1-yl)ndimethylacetamide
- N-(((3S,5S)-3-(4-aminobutyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (S)-N-(((3S,5S)-3-(4-aminobutyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
- (R)-N-(((3S,5S)-3-(4-aminobutyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxym the d
- N-(((3S,5S)-3-(4-aminobutyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-benzofuran-2-carboxamide
- (R)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-(3-methylguanine)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
- (S)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)benzofuran-2-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2,3-dihydro-1H-inden-2-carboxamid
- (R)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)benzo[b]thiophene-2-carboxamid
- 2,4-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- 2,5-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)benzamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)cyclohexanecarboxylic
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-phenoxybenzamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-4-Fe is oxybenzone
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-1H-indole-2-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-phenylpropanamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-3,4-dimethylbenzamide
- 4-tert-butyl-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2,4-dimethoxybenzamide
- 2-cyclohexyl-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)ndimethylacetamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)benzo[d][1,3]dioxol-5-carboxamid
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-1H-benzo[d]imidazol-5-carboxamid
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-1H-benzo[d][1,2,3]triazole-5-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)cyclopentanecarboxylic
3,4 - dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)cinnamamide
- 3,5-dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- 2-(2,4-dichlorophenyl)-N-(((3S,5S)-1-(2,2-given later)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)ndimethylacetamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-1-methoxy-2-naptime
- 2-(3,4-dichlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)ndimethylacetamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-6-methoxy-2-naptime
- (E)-3-(2,4-dichlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-adamantane-1-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-phenoxyacetamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-methoxy-2-naptime
- 4-bromo-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- (S)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-carboxamid
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(thiophene-2-yl)acrylamide
- (R)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-2-carboxamid
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-hydroxyphenyl)AK is ilamed
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2-methoxyphenyl)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-p-tolylacetate
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2-(trifluoromethyl)phenyl)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(3-forfinal)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-methyl-3-phenylacrylate
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-phenylcyclopropanecarboxylic
- 2-(2,4-dichlorophenoxy)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)ndimethylacetamide
- (E)-3-(3-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)benzo[d]thiazol-6-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-5-phenylfuro-2-carboxamid
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(3-methoxyphenyl)acrylamide
- 6-bromo-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-phenethyl-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,S)-1-(3,4-dichlorophenacyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-1-(2,4-dichlorophenacyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)benzo[b]thiophene-5-carboxamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-methoxyphenyl)acrylamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-6-fluoro-2-naptime
- (E)-3-(2-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2-hydroxyphenyl)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-m-tolylacetic
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(3-(trifluoromethyl)phenyl)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(3-hydroxyphenyl)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(2-forfinal)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-o-tolylacetate
- (Z)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-fluoro-3-phenylace the amide
- N-((1-(2,2-diphenylether)-2-oxo-3-(piperidine-4-yl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-((1-(2,2-diphenylether)-2-oxo-3-(piperidine-4-ylmethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-(trifluoromethyl)phenyl)acrylamide
- N-(((3S,5S)-1-(2,2-diphenylpropyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(cyclohexylmethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-1-(1-adamantylamine)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-1-((S)-1,1-diphenylpropane-2-yl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-((R)-1,1-diphenylpropane-2-yl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-cyclohexyl-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-((R)-1-fluoro-1,1-diphenylpropane-2-yl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-3-(2,6-differenl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-3-(2-chloro-6-forfinal)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-3-(4-bromophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)AK is ilamed
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-ethoxyphenyl)acrylamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-cinnamamide
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-chlorophenyl)acrylamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-1,4-dimethoxy-2-naptime
- N-(((3S,5S)-3-(3-(3,3-dimethylguanidine)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-6-hydroxy-2-naptime
- 6-amino-N-(((3S,5S)-1-(2,2-diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-p-tolylacetate
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-forfinal)acrylamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-ethylhexanate
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dimethylbenzamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- N-(((3S,5S)-1-(2,diphenylether)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-ethylhexanate
- N-(((3S,5S)-3-(3-(cyclohexylamino)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-guanidinopropionic)-1-(naphthalene-2-yl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-1-((9H-fluoren-9-yl)methyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-3-(3-(cyclohexylamino)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(4-(isopropylamino)butyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(2,4-differenl)acrylamide
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-cyanophenyl)acrylamide
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(naphthalene-2-yl)acrylamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-(4-pertenece)ndimethylacetamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-5-(4-chlorophenyl)furan-2-carboxamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-4-(1H-pyrrol-1-yl)benzamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-oxo-1-phenylpyrrolidine-3-carboxamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-5-(4-chlorophenyl)isoxazol-3-carboxamid
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-dif is niatel)-2-oxo-1,4-diazepan-5-yl)methyl)-5-(furan-2-yl)isoxazol-3-carboxamid
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-phenylthiazol-4-carboxamid
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-4-(3,5-dimethyl-1H-pyrazole-1-yl)benzamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide
- N-(((3S,5S)-1-(2-cyclohexylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-1-(2-(bicyclo[2.2.1]heptane-2-yl)ethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-bis(4-methoxyphenyl)ethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-(benzylamino)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-(cyclopentylamine)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-(cyclobutylamine)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-(dicycloverine)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-benzyl-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-bis(4-forfinal)ethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-guanidinopropionic)-1-(naphthalene-2-ylmethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(5-METI the thiophene-2-yl)acrylamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-phenyl-1H-pyrazole-5-carboxamide
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-forfinal)-N-methylacrylamide
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-4-methyl-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-yl)benzamide
- (E)-N-(((3S,5S)-3-(3-aminopropyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-bromophenyl)acrylamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(pyrrolidin-1-yl)-propyl)-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)-propyl)-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(pyrrolidin-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-(azetidin-1-yl)propyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-guanidinopropionic)-1-(naphthalene-1-ylmethyl)-2-oxo-1,4-diazepan-6-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-guanidinopropionic)-1-(2-(naphthalene-2-yl)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-((S)-2-acetamido-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)cinnamamide
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-3,4-dimethylbenzamide
3,4 - dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-1-((S)-2-(cyclobutanecarboxylic)-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-((S)-2-(cyclohexanecarboxylate)-2-phenylethyl)-3-(3-guanidino-propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(aminomethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-3-(aminomethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-chlorophenyl)acrylamide
- (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-forfinal)acrylamide
- (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-p-tolylacetate
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)-methyl)-2-naptime
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(piperidine-1-yl-methyl)-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dimethylbenzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-cinnamamide
- (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-chlorophenyl)is Grilamid
3,4 - dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3,4-dimethylbenzamide
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)cinnamamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-(4-forfinal)acrylamide
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-p-tolylacetate
- N-(((3S,5S)-1-(3,5-dimethylbenzyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-1-((S)-2-benzamido-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-((R)-2-benzamido-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-guanidinopropionic)-1-(2-methoxy-2-phenylethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-(2-phenyl-2-propoxyethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2-(benzyloxy)-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2-(allyloxy)-2-phenylethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-3-(3-acetamidophenyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-p-tolylacetate
- N-(3-((2S,7S)-4-(2,2-diphenylether)-3-oxo-7-((E)-3-p-tolylamino)methyl)-1,4-diazepan the-2-yl)propyl)cyclohexanecarboxylic
- N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-(2-phenoxy-2-phenylethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- ethyl 3-((3S,5S)-5-((2-naphthalide)methyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-1-yl)-2-phenylpropanoate
- N-(((3S,5S)-1-(2-ethylbutyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-((3,5-dimethylcyclohexyl)methyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(2-((2S,7S)-7-((E)-3-(4-chlorophenyl)acrylamide)methyl)-4-(2,2-diphenylether)-3-oxo-1,4-diazepan-2-yl)ethyl)cyclohexanecarboxylic
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(2-cyclohexylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-amino-ethyl)-1,4-diazepan-5-yl)ethyl)-benzamide
3,4 - dichloro-N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-amino-ethyl)-1,4-diazepan-5-yl)ethyl)benzamide
- N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-amino-ethyl)-1,4-diazepan-5-yl)ethyl)-2-naptime
- N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)ethyl)benzamide
3,4 - dichloro-N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)ethyl)benzamide
- N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)ethyl)-2-naptime
- N-(((3S,5S)-1-(3-(dimethylamino)-3-oxo-2-phenylpropyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- (E)-N-((3S,5S)-3-(2-amino-ethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-chlorophenyl)acrylamide
- N-(((3S,5S)-1-(3-chloro-5-terbisil)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(3,5-diferensial)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(3-chloro-5-terbisil)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(3,5-diferensial)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,6-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(3,5-dimethoxybenzyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2-Chlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,3-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(2,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(3,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(3-fluoro-5-methylbenzyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(3-fluoro-5-(trifluoromethyl)benzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(4-Chlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((1-paneltitle exil)methyl)-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
3,4 - dichloro-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-4-chloro-3-perbenzoic
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-4-chloro-3-methylbenzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-chloro-4-perbenzoic
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-chloro-4-methylbenzamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- N-(2-((3S,5R)-1-(2,2-diphenylether)-2-oxo-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)ethyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(3,5-is IP(trifluoromethyl)benzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(3-Chlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-2-oxo-1-(2-phenylbutyl)-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-(3-oxo-2-phenyl-3-(piperidine-1-yl)-propyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-guanidinopropionic)-2-oxo-1-(3-oxo-2-phenyl-3-(phenylamino)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(2-((3S,5R)-1-(2,2-diphenylether)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)ethyl)benzamide
3,4 - dichloro-N-(2-((3S,5R)-3-(2-(diisopropylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)ethyl)benzamide
- N-(((3S,5S)-3-(aminomethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- N-(((3S,5S)-3-(aminomethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-3-(aminomethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(4-chlorophenyl)acrylamide
3,4 - dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)benzamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(piperidine-1-yl-methyl)-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- (E)-N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide
3,4 - dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(pyrrolidin-1-ylmethyl)-1,4-diazepan-5-yl)methyl)benzo the ID
- N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(pyrrolidin-1-ylmethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((S)-2-phenylpropyl)-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((R)-2-phenylpropyl)-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(2-(dimethylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-1-(3,5-diethylphenyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(diethylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-3-(2-(diethylamino)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-those who butyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethylbutyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-bromo-2-naptime
- N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)-methyl)-6-fluoro-2-naptime
- 6-chloro-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-bromo-N-(((3S,5S)-1-(2-ethylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-((3,5-dimethylcyclohexyl)methyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-((3,5-dimethylcyclohexyl)methyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-((3,5-dimethylcyclohexyl)methyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)acrylamide
- 6-chloro-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-6-fluoro-2-naptime
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(pyrrolidin-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-ylmethyl)benzamide
- N-(((3S,5S)-3-(3-aminopropyl)-1-((2,6-dimethylcyclohexyl)methyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)-methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-1-((3,5-dimethylcyclohexyl)methyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-1-((3,5-dimethylcyclohexyl)methyl)-3-(2-(isopropylamino)-ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(3-methyl-2-phenylbutyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(3-aminopropyl)-2-oxo-1-((R)-2-phenylbutyl)-1,4-diazepan-5-yl)-methyl)-2-naptime
- 3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)propanamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(4-chlorophenyl)propanamide
- N-(((2S,7S)-7-((E)-3-(4-chlorophenyl)acrylamide)methyl)-4-(2,2-diphenylether)-3-oxo-1,4-diazepan-2-yl)methyl)picolinate
- N-(((3S,5S)-1-((R)-3-methyl-2-phenylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-((3)-3-methyl-2-phenylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-(4-isopropylphenyl)acrylamide
- (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-IU who yl)-3-(4-isopropylphenyl)acrylamide
- (E)-3-(2,4-dimetilfenil)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(2,4-dimetilfenil)acrylamide
- (E)-3-(2,4-differenl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-methyl)-3-(2,4-differenl)acrylamide
- N-(((2S,7S)-7-((E)-3-(4-chlorophenyl)acrylamide)methyl)-4-(2,2-diphenylether)-3-oxo-1,4-diazepan-2-yl)methyl)cyclohexanecarboxylic
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-morpholinoethyl)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(2,5-dimethyl-1H-pyrrol-1-yl)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(2,5-dimethylpiperidin-1-yl)ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)acrylamide
- 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(pyrrolidin-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- (E)-3-(4-chlorophenyl)-N-(((3S,5S)-3-(2-(isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)acrylamide
- 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-the l)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
is benzyl ((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methylcarbamate
- (E)-3-(4-bromophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)acrylamide
- 5-(4-chlorophenyl)-N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)isoxazol-3-carboxamid
- 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(piperidine-1-ylmethyl)-1,4-diazepan-5-yl)methyl)benzamide
- 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(3-(piperidine-1-yl)propyl)-1,4-diazepan-5-yl)methyl)benzamide
- (E)-N-(2-((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)-propan-2-yl)-3-(4-chlorophenyl)acrylamide
- (E)-3-(4-chlorophenyl)-N-(2-((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)propan-2-yl)acrylamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-((R)-2-(4-chlorophenyl)propyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-(4-chlorophenyl)propyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-naptime
- N-(((3S,5S)-1-((R)-2-(4-chlorophenyl)propyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-((S)-2-(4-chlorophenyl)propyl)-2-oxo-3(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-3-(2-(methyl(phenyl)amino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-(diethylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-morpholinoethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-2-oxo-3-(2-(phenylamino)ethyl)-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-3-(2-(benzylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- N-(((3S,5S)-3-(2-(tert-butylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-(4-methylpiperazin-1-yl)ethyl)-2-oxo-1-((S)-2-phenyl-butyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-2-oxo-1-((R)-2-fenilpentil)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-2-oxo-1-((S)-2-fenilpentil)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-4-(trifluoromethyl)benzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-4-(trifluoromethyl)benzamide
- N-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-(trifluoromethyl)benzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,2-diphenylether)-2-oxo-1,4-diazepan-5-yl)methyl)-3-(trifluoromethyl)benzamide
- 6-chloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(2-(isopropylamino)ethyl)-2-oxo-1,diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(2-(isopropylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- 6-chloro-N-(((3S,5S)-3-(2-(isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime
- N-(((3S,5S)-3-(2-(benzyl(methyl)amino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
3,4 - dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperazine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-(methyl(pentyl)amino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-(diisopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-(4-methylpiperidin-1-yl)ethyl)-2-oxo-1-((S)-2-phenyl-butyl)-1,4-diazepan-5-yl)methyl)benzamide
- (S)-6-chloro-N-((2-oxo-1-(2-phenylbutyl)-3-(piperidine-4-yl)-1,4-diazepan-5-yl)-methyl)-2-naptime
- (S)-6-chloro-N-(3-(1-isopenicillin-4-yl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-3-(2-(3,5-dimethylpiperidin-1-yl)ethyl)-2-oxo-1-((S)-2-phenyl-butyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-(4-hydroxypiperidine-1-yl)ethyl)-2-oxo-1-((S)-2-phenyl-butyl)-1,4-diazepan-5-yl)methyl)benzamide
- 1-(2-((2S,7S)-7-((3,4-dichlorobenzamide)methyl)-3-oxo-4-((S)-2-phenylbutyl)-1,4-diazepan-2-yl)ethyl)piperidine-4-carboxylic acid
- N-(((3S,5S)-3-(2-(azepin-1-yl)et is l)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)-methyl)-3,4-dichlorobenzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-((S)-2-methylpiperidin-1-yl)ethyl)-2-oxo-1-((S)-2-phenyl-butyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-3-(2-(tert-butyl(methyl)amino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- 6-chloro-N-((3-(1-ethylpiperazin-4-yl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)-methyl)-2-naptime
- (3S,5S)-5-((3,4-dichloraniline)methyl)-1-(2,2-diphenylether)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-2-he
- 6-chloro-N-(((3S,5S)-3-(2-guanidinate)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-3-(2-(3-methylguanine)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-((R)-2-ethyl-3-methylbutyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-3,4-dichlorobenzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-((S)-2-ethyl-3-methylbutyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-3,4-dichlorobenzamide
3,4 - dichloro-N-(((3S,5S)-1-((R)-2-ethyl-3-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-1-((S)-2-ethyl-3-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-3-(2-amino-2-methylpropyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-(isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(3,5-dichlorobenzyl)-2-oxo-1,4-diazepan-5-is)methyl)-6-chloro-2-naptime
- 6-chloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-3-(2-methyl-2-(piperidine-1-yl)propyl)-2-oxo-1-((S)-2-phenyl-butyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-((R)-2-ethyl-3-methylbutyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-6-chloro-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-((S)-2-ethyl-3-methylbutyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-6-chloro-2-naptime
- 6-chloro-N-(((3S,5S)-1-((R)-2-ethyl-3-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-1-((S)-2-ethyl-3-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-(((3S,5S)-1-(2,2-diphenylether)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methylcarbamoyl)-2-naphthoic acid
- 6-chloro-N-(((3S,5S)-3-(2-(3-isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethyl-3-methylbut-3-enyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-3,4-dichlorobenzamide
3,4 - dichloro-N-(((3S,5S)-1-(2-ethyl-3-methylbut-3-enyl)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethyl-3-methylbut-3-enyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-6-chloro-2-naptime
- 6-chloro-N-(((3S,5S)-1-((R)-2-ethyl-3-methylbut-3-enyl)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-1-((S)-2-ethyl-3-methylbut-3-enyl)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-1-(cycle shall heximer)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl) - biphenyl-4-carboxamid
- N-(((3S,5S)-1-(cyclohexylmethyl)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)-2-(1H-indol-3-yl)ndimethylacetamide, and
- N-(((3S,5S)-1-(temporarilly)-3-(3-guanidinopropionic)-2-oxo-1,4-diazepan-5-yl)-methyl)quinoline-3-carboxamide.

20. A compound selected from the group consisting of the following compounds:
3,4 - dichloro-N-(((3S,5S)-3-(2-(4,4-deformability-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-(3,3-deformability-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
- (3S,5S)-5-((3,4-dichloraniline)methyl)-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-2-he
3,4 - dichloro-N-(((3S,5S)-1-(2-cyclopropylethyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-cyclopropylethyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-6-chloro-2-naptime
- 6-chloro-N-(((3S,5S)-1-(2-cyclopropylethyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-3-(2-(2,5-dioxopiperidin-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
- 6-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(3-ureidopropionic)-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(1,1,1-tryptophan-2-ylamino)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-3-(2-(3,3-dimethyl-2,5-dioxopiperidin-1-yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-3-(2-(ASEAN--yl)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)-methyl)-6-chloro-2-naptime
- 6-chloro-N-(((3S,5S)-3-(2-(3-isopropylamino)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)biphenyl-4-carboxamid
- N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-phenylthiazol-4-carboxamid
- 4'-chloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)biphenyl-2-carboxamide
- 6-chloro-N-(((3S,5S)-3-(2-(N-isopropylacrylamide)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-3-((isopropylamino)methyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-3-(guanidinate)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 2-(2,4-dichlorophenyl)-N-(((3S,5S)-2-oxo-1-((5)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)ndimethylacetamide
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
3,4 - dichloro-N-(((3S,5S)-1-(2,4-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-1-(2,4-dichlorobenzyl)-3-(2-(methylsulfonylamino)ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
3,4 - dichloro-N-(((3S,5S)-1-(2,4-dichlorobenzyl)-3-(2-(4-methylphenylsulfonyl)-ethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-3-(2-((S)-2-amino-3-methylbutanoate)ethyl)-1-(2,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-3,4-dichlorobenzamide
- N-((3S,5S)-3-(2-amino-ethyl)-1-(2,4-dichlorobenzyl)-2-oxo-1,4-diazepan-5-yl)methyl)-6-chloro-2-naptime
- 6-chloro-N-(((3S,5S)-1-(2,4-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-2-oxo-1-(2-(thiophene-3-yl)butyl)-1,4-diazepan-5-yl)-methyl)-6-chloro-2-naptime
- 6-chloro-N-(((3S,5S)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1-((R)-2-(thiophene-3-yl)butyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1-((S)-2-(thiophene-3-yl)butyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethyl-2-methylbutyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-6-chloro-2-naptime
- 6-chloro-N-(((3S,5S)-1-(2-ethyl-2-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-1-(2,2-diphenylether)-3-(2-morpholinoethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-3-(2-morpholinoethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(2-morpholinoethyl)-2-oxo-1,4-diazepan-5-yl)methyl)-2-naptime
3,4 - dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-3-(2-morpholinoethyl)-2-oxo-1,4-diazepan-5-yl)methyl)benzamide
- N-(3,4-dichlorobenzyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)ndimethylacetamide
- 1-(4-Chlorobenzyl)-3-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)urea
- N-(((3S,5S)-3-(2-amino-ethyl)-1-(2-ethyl-2-methylbutyl)-2-oxo-1,4-diazepan-5-yl)-methyl)-3,4-dichlorobenzamide
3,4 - dichloro-N-(((3S,5S)-1-(2-ethyl-2-methylbutyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diaza the h-5-yl)methyl)benzamide
- 6-chloro-N-(((3S,5S)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1-(2,3,5-trichlorobenzoyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-3-(2-(1-methylethanolamine)ethyl)-2-oxo-1-((S)-2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- butyl 2-((2S,7S)-7-((6-chloro-2-naphthalide)methyl)-3-oxo-4-((S)-2-phenylbutyl)-1,4-diazepan-2-yl)ethylcarbamate
- (S)-6-chloro-N-((3-(1-isopropylpiperazine-4-yl)-2-oxo-1-(2-phenylbutyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 6-chloro-N-(((3S,5S)-2-oxo-1-((R)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 5-(4-chlorophenyl)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)isoxazol-3-carboxamid
- 2,4-dichloro-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
- N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-6-methoxy-2-naptime
- 6-chloro-N-(([a 513C,the 415N](3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)[13C]methyl)-2-naptime
- N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-1-methoxy-2-naptime
- (E)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-(4-(triptoreline)phenyl)acrylamide
- 5-(4-chlorophenyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)methyl)isoxazol-3-carboxamid
- 2,4-dichloro-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-yl)ethyl)-1,4-diazepan-5-yl)methyl)benzamide
- 5,6-dichloro-2-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)isoindoline-1,3-dione
- (E)-N-(((3S,5S)-1-(3,5-dichlorobenzyl)-2-oxo-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-3-(3-fluoro-4-(triptoreline)phenyl)acrylamide
- 6-methoxy-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- 1-methoxy-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)-2-naptime
- (E)-3-(3-fluoro-4-(triptoreline)phenyl)-N-(((3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)ethyl)-1,4-diazepan-5-yl)methyl)acrylamide and
- 6-chloro-N-(([5,6,6-2H3](3S,5S)-2-oxo-1-((S)-2-phenylbutyl)-3-(2-(piperidine-1-yl)-ethyl)-1,4-diazepan-5-yl)[2H2]methyl)-2-naptime.

21. Pharmaceutical composition for treatment of a condition associated with MC5R containing compound according to any one of claims 1 to 20 and a pharmaceutically acceptable carrier, diluent or excipient.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a novel derivative of N-acylanthranilic acid, represented by the following general formula 1, or to its pharmaceutically acceptable salt, in which R1, R2, R3, X1, X2, X3, X4 and A are determined in the invention formula.

EFFECT: invention relates to an inhibitor of collagen production, a medication for treating diseases, associated with the excessive production of collagen, containing N-acylanthranilic acid derivative Formula 1.

FIELD: chemistry.

SUBSTANCE: invention relates to a photoinitiator, a method for production and use thereof and a coating composition. The photoinitiator is a compound of formula: (PI-Sp)n-BB (I), where PI is a thioxanthone group, optionally including additional substitutes in the Sp group; Sp is a spacer link selected from a group consisting of or , BB is a backbone chain link selected from a group consisting of

The method of producing the photoinitiator includes the following steps: (a) optionally substituted thioxanthone, containing at least one hydroxy group, reacts with epichlorohydrin or haloacetic acid ester; (b) the compound from step (a) reacts with the corresponding backbone chain link containing a functional group, or the compound from step (a) reacts with a compound containing a functional group, and the obtained intermediate then reacts with the corresponding backbone chain link; optionally (c) obtaining derivatives of the compounds from step (b). The photoinitiator is used to cure a coating composition, preferably printing ink containing a polymerisable component.

EFFECT: invention enables to obtain a photoinitiator with good curing activity, faint odour and good compatibility with other components of the composition.

10 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula

,

wherein: each of R1, R2, R4, R5, R6, R7, R8 R9, R10, R11, R12, R13, R14, R15 R16 and R17 is independently specified in a group consisting of deuterium or hydrogen; and R3 is independently specified in a group consisting of CD3 and CH3; provided R3 represents CH3, at least one of the groups R1, R2, R4, R5, R6, R7, R8 R9, R10, R11, R12, R13, R14, R15 R16 and R17 represents deuterium; and R18 represents hydrogen. The invention also refers to a drug on the basis of the above compound for treating a condition causing pain.

EFFECT: there are prepared new compounds inhibiting MMPs (metalloproteinases) which show the high activity, metabolic stability and/or lower toxicity in relation to the currently known MMP inhibitors for treating pain and other diseases, such as cancer.

16 cl, 2 dwg, 14 tbl, 136 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 6-substituted isoquinoline and isoquinolinone derivatives of formula or to its stereoisomer and/or tautomer forms and/or a pharmaceutically acceptable salt, wherein R1 represents H, OH or NH2; R3 represents H; R4 represents H, a halogen atom, CN or (C1-C6)alkylene-(C6-C10)aryl; R5 represents H, a halogen atom, (C1-C6)alkyl; R7 represents H, a halogen atom, (C1-C6)alkyl, O-(C1-C6)alkyl; R8 represents H; R9 and R6 are absent; R10 represents (C1-C6)alkyl, (C1-C8)heteroalkyl, (C3-C8)cycloalkyl, (C6)hetrocycloalkyl, (C1-C6)alkylene-(C3-C8)cycloalkyl, (C1-C6)alkylene-(C6-C10)aryl, (C1-C6)alkylene-(C6)heterocycloalkyl; R11 represents H; R12 represents (C1-C6)alkyl, (C3-C8)cycloalkyl, (C5)heteroaryl or (C6-C10)aryl; R13 and R14 independently represent H, (C1-C6)alkyl, (C1-C6)alkylene-R'; n is equal to 0; m is equal to 2 or 3; s is equal to 1 or 2; r is equal to 1; L represents O or NH; R' represents (C3-C8)cycloalkyl, (C6-C10)aryl; wherein in the rests, R10, R12-R14 alkyl or alkylene are unsubstituted or optionally substituted by one or more OCH3; wherein in the rests, R10, R12-R14 alkyl or alkylene are unsubstituted or optionally substituted by one or more halogen atoms; wherein (C1-C8)heteroaryl group means (C1-C8)alkyl groups, wherein at least one carbon atom is substituted by O;. (C6)heterocycloalkyl group means a monocyclic carbon ring system containing 6 ring atoms wherein one carbon atom can be substituted by 1 oxygen atom or 1 sulphur atom which can be optionally oxidated; (C5)heteroaryl means a monoring system wherein one or more carbon atoms can be substituted by 1 nitrogen atom or 1 sulphur atom or a combination of various heteroatoms. Also, the invention refers to using the compound of formula (I) and to a therapeutic agent based on the compound of formula (I).

EFFECT: there are prepared new compounds effective for treating and/or preventing diseases associated with Rho-kinase and/or mediated by Rho-kinase by phosphorylation of myosin light chain phosphatase, and the compositions containing these compounds.

32 cl, 111 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula or to its therapeutically acceptable salt, where A1 represents N or C(A2); A2 represents H; B1 represents H, OR1 or NHR1; D1 represents H; E1 represents H; Y1 represents CN, NO2, F, Cl, Br, I, R17 or SO2R17; R1 represents R4 or R5; Z1 represents R26 or R27; Z2 represents R30; Z1A and Z2A both are absent; L1 represents R37; R26 represents phenylene; R27 represents indolyl; R30 represents piperasinyl; R37 represents R37A; R37A represents C2-C4 alkylene; Z3 represents R38, R39 or R40; R38 represents phenyl; R39 represents benzodioxilyl; R40 represents C4-C7cycloalkenyl, heterocycloalkyl, which represents monocyclic six- or seven-member ring, containing one heteroatom, selected from O, and zero of double bonds, or azaspiro[5.5]undec-8-ene; the remaining values of radicals are given in i.1 of invention formula. Invention also relates to pharmaceutical composition, based on claimed compound.

EFFECT: novel compounds, which can be applied in medicine for treatment of diseases, in the process of which anti-apoptotic Bcl-2 protein is expressed, are obtained.

8 cl, 2 tbl, 411 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compounds can find application for preventing or treating cancer, lung cancer, non-small cells lung cancer, small-cell lung cancer, EML4-ALK hybrid polynucleotide-positive cancer, EML4-ALK hybrid polynucleotide-positive lung cancer or EML4-ALK hybrid polynucleotide-positive non-small cells lung cancer. In formula (I) -X-: group of formula , A represents chlorine, ethyl or isopropyl; R1 represents phenyl wherein carbon in the 4th position is substituted by the group -W-Y-Z, and carbon in the 3rd position can be substituted by a group specified in a group consisting of halogen, R00 and -O-R00; R00: lower alkyl which can be substituted by one or more halogen atoms; -W-: a bond, piperidine-1,4-diyl or piperazine-1,4-diyl; -Y- represents a bond; Z represents a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more substitutes R00; R2 represents (i) an optionally bridged saturated C3-10cycloalkyl which can be substituted by one or more groups specified in -N(lower alkyl)2, lower alkyl, -COO-lower alkyl, -OH, -COOH, -CONH-RZB and morpholinyl, or (ii) a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more groups specified in a group consisting of lower alkyl, -CO-lower alkyl, oxo, -CO-RZB and benzene; and RZB: phenyl which can be substituted by a group consisting of halogen and -O-lower alkyl; R3 represents -H.

EFFECT: invention refers to new compounds of formula or their pharmaceutically acceptable salts possessing the properties of a selective inhibitor of EML4-ALK hybrid protein kinase activity.

16 cl, 201 tbl, 582 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to methods of treating or relieving severity of disease in patient, where disease is selected from mucoviscidosis, hereditary emphysema, chronic obstructive pulmonary disease (COPD), "dry eye" disease. Methods include introduction of effective amount of N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or pharmaceutical composition, containing said compound, to patient.

EFFECT: treatment of relief of disease severity in patient, where disease is selected from mucoviscidosis, hereditary emphysema, chronic obstructive pulmonary disease (COPD), "dry eye" disease.

16 cl, 15 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel fungicidally active 5-fluoropyrimidines of general formula I. In compounds of formula , R1 is -N(R3)R4; R2 is -OR21; R3 is: H; C1-C6-alkyl, optionally substituted with 1-3 groups R5; C2-C6-alkenyl, optionally substituted with 1-3 groups R5; a 5- or 6-member heteroaromatic cycle, selected from a group consisting of furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl; wherein each heteroaromatic cycle is optionally substituted with 1-3 R29 groups; 3H-isobenzofuran-1-oyl; -C(=O)R6; -C(=S)R6; -C(=S)NHR8; -(=O)N(R8)R10; -OR7; -P(O)(OR15)2; -S(O)2R8;-SR8; -Si(R8)3; -N(R9)R10; -(CHR24)mOR29 or -C(=NR16)SR16; where m equals an integer from 1 to 3; R4 is: H; C1-C6-alkyl, optionally substituted with 1-3 R5 groups; or -C(=O)R6; alternatively, R3 and R4 together can form: a 5- or 6-member saturated or unsaturated cycle containing 1-2 heteroatoms selected from N and O, where each cycle can be optionally substituted with 1-3 R11 groups; =C(R12)N(R13)R14 or =C(R15)OR15. The rest of the radicals are given in the claim.

EFFECT: obtaining novel fungicidally active 5-fluoropyrimidines of general formula I.

4 cl, 3 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 5-membered heterocyclic compounds of general formula (I), their prodrugs or pharmaceutically acceptable salts, which possess xanthine oxidase inhibiting activity. In formula (I) T represents nitro, cyano or trifluoromethyl; J represents phenyl or heteroaryl ring, where heteroaryl represents 6-membered aromatic heterocyclic group, which has one heteroatom, selected from nitrogen, or 5-membered aromatic heterocyclic group, which has one heteroatom, selected from oxygen; Q represents carboxy, lower alkoxycarbonyl, carbomoyl or 5-tetrasolyl; X1 and X2 independently represent CR2 or N, on condition that both of X1 and X2 do not simultaneously represent N and, when two R2 are present, these R2 are not obligatorily similar or different from each other; R2 represents hydrogen atom or lower alkyl; Y represents hydrogen atom, hydroxy, amino, halogen atom, perfluoro(lower alkyl), lower alkyl, lower alkoxy, optionally substituted with lower alkoxy; nitro, (lower alkyl)carbonylamino or (lower alkyl) sulfonylamino; R1 represents perfluoro(lower alkyl), -AA, -A-D-L-M or -A-D-E-G-L-M (values AA, A, D, E, G, L, M are given in i.1 of the invention formula).

EFFECT: invention relates to xanthine oxidase inhibitor and pharmaceutical composition, which contain formula (I) compound.

27 cl, 94 tbl, 553 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted pyrrolidine-2-carboxamides of formula I or their pharmaceutically acceptable salts, where values X, Y, R1, R2, R3, R3, R4, R5, R6 and R7 are given in item 1 of the formula. Compounds can be used in pharmaceutical composition, inhibiting interaction of MDM2-p53.

EFFECT: compounds can be used as anti-cancer medications.

46 cl, 4 dwg, 347 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: in general formula A1 stands for CR10R11 or S; A2 stands for CR12R13, C(=O), O, S or S(=O)2; R1 stands for C1-10-alkyl, saturated or unsaturated, branched or non-branched, non-substituted, or monosubstituted, or polysubstituted; C3-10-cycloalkyl or 5- or 6-membered heterocyclyl with the O-atom, each time saturated or unsaturated, non-substituted, or monosubstituted, or polysubstituted; C6-10-aryl or C5-10-heteroaryl with 1-3 heteroatoms, selected from N, O or S, each time non-substituted, or monosubstituted, or polysubstituted; through C1-8-alkyl or C2-8-heteroalkyl bound by the bridge bond C3-10-cycloalkyl, each time saturated, non-substituted, and the alkyl or heteroalkyl chain each time can be branched or non-branched, saturated, non-substituted; or through C1-8-alkyl, bound by the bridge bond aryl or heteroaryl, each time non-substituted, or monosubstituted, or polysubstituted, and the alkyl chain each time can be branched or non-branched, saturated or unsaturated, non-substituted, or monosubstituted, or polysubstituted; R2, R3 and R4 each time independently on each other stand for H; F; Cl; Br; I; methyl; O-C1-6-alkyl or NRaRb, and Ra and Rb together with the nitrogen atom that binds them form heterocyclyl, saturated, non-branched, non-substituted; R5, R6, R7, R8, R10, R11, R12 and R13each time independently on each other stand for H; F; Cl; Br; I; OH or C1-10-alkul; or R5 and R6 or R7 and R11 together with carbon atom(s), that bind(s) them form C3-8-cycloalkyl, each time saturated or non-saturated, non-substituted, or monosubstituted, or polysubstituted; with respective remaining substituents R5, R6, R7, R8, R10, R11, R12 and R13 having the value given above; R9 stands for C3-10-cycloalkyl, saturated, non-substituted; C6-10-aryl or 5- or 6-membered heteroaryl with heteroatom, selected from N and S, each time non-substituted or monosubstituted.

EFFECT: invention relates to substituted nicotinamides of general formula (1), to a medication based on them and their application for treating KCNQ2/3-mediated diseases.

13 cl, 3 tbl, 224 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 6-substituted isoquinoline and isoquinolinone derivatives of formula or to its stereoisomer and/or tautomer forms and/or a pharmaceutically acceptable salt, wherein R1 represents H, OH or NH2; R3 represents H; R4 represents H, a halogen atom, CN or (C1-C6)alkylene-(C6-C10)aryl; R5 represents H, a halogen atom, (C1-C6)alkyl; R7 represents H, a halogen atom, (C1-C6)alkyl, O-(C1-C6)alkyl; R8 represents H; R9 and R6 are absent; R10 represents (C1-C6)alkyl, (C1-C8)heteroalkyl, (C3-C8)cycloalkyl, (C6)hetrocycloalkyl, (C1-C6)alkylene-(C3-C8)cycloalkyl, (C1-C6)alkylene-(C6-C10)aryl, (C1-C6)alkylene-(C6)heterocycloalkyl; R11 represents H; R12 represents (C1-C6)alkyl, (C3-C8)cycloalkyl, (C5)heteroaryl or (C6-C10)aryl; R13 and R14 independently represent H, (C1-C6)alkyl, (C1-C6)alkylene-R'; n is equal to 0; m is equal to 2 or 3; s is equal to 1 or 2; r is equal to 1; L represents O or NH; R' represents (C3-C8)cycloalkyl, (C6-C10)aryl; wherein in the rests, R10, R12-R14 alkyl or alkylene are unsubstituted or optionally substituted by one or more OCH3; wherein in the rests, R10, R12-R14 alkyl or alkylene are unsubstituted or optionally substituted by one or more halogen atoms; wherein (C1-C8)heteroaryl group means (C1-C8)alkyl groups, wherein at least one carbon atom is substituted by O;. (C6)heterocycloalkyl group means a monocyclic carbon ring system containing 6 ring atoms wherein one carbon atom can be substituted by 1 oxygen atom or 1 sulphur atom which can be optionally oxidated; (C5)heteroaryl means a monoring system wherein one or more carbon atoms can be substituted by 1 nitrogen atom or 1 sulphur atom or a combination of various heteroatoms. Also, the invention refers to using the compound of formula (I) and to a therapeutic agent based on the compound of formula (I).

EFFECT: there are prepared new compounds effective for treating and/or preventing diseases associated with Rho-kinase and/or mediated by Rho-kinase by phosphorylation of myosin light chain phosphatase, and the compositions containing these compounds.

32 cl, 111 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula or to its therapeutically acceptable salt, where A1 represents N or C(A2); A2 represents H; B1 represents H, OR1 or NHR1; D1 represents H; E1 represents H; Y1 represents CN, NO2, F, Cl, Br, I, R17 or SO2R17; R1 represents R4 or R5; Z1 represents R26 or R27; Z2 represents R30; Z1A and Z2A both are absent; L1 represents R37; R26 represents phenylene; R27 represents indolyl; R30 represents piperasinyl; R37 represents R37A; R37A represents C2-C4 alkylene; Z3 represents R38, R39 or R40; R38 represents phenyl; R39 represents benzodioxilyl; R40 represents C4-C7cycloalkenyl, heterocycloalkyl, which represents monocyclic six- or seven-member ring, containing one heteroatom, selected from O, and zero of double bonds, or azaspiro[5.5]undec-8-ene; the remaining values of radicals are given in i.1 of invention formula. Invention also relates to pharmaceutical composition, based on claimed compound.

EFFECT: novel compounds, which can be applied in medicine for treatment of diseases, in the process of which anti-apoptotic Bcl-2 protein is expressed, are obtained.

8 cl, 2 tbl, 411 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel chromenone derivatives of formula II or its pharmaceutically acceptable salts, where each R20 is hydrogen; R11 is selected from phenyl and 5-6 member saturated or aromatic heterocycle, including one or two heteroatoms, selected from N, O or S, where R11 is optionally substituted with one-two substituents, independently selected from C1-C4alkyl, =O, -O-R13, -(C1-C4alkyl)-N(R13)(R13), -N(R13)(R13), where each R13 is independently selected from hydrogen and -C1-C4alkyl; or two R13 together with nitrogen atom, to which they are bound, form 5-6-member saturated heterocycle, optionally including one additional O, where, when R13 is alkyl, alkyl is optionally substituted with one or more substituents, selected from -OH, fluorine, and, when two R13 together with nitrogen atom, to which they are bound, form 6-member saturated heterocycle, saturated heterocycle is optionally substituted on each carbon atom with -C1-C4alkyl; R12 is selected from phenyl and pyridyl, where R12 is optionally substituted with one or more substituents, independently selected from halogen, C1-C4alkyl, C1-C2 fluorine-substituted alkyl, -O-R13, -S(O)2-R13, -(C1-C4alkyl)-N(R13)(R13), -N(R13)(R13); R14 is selected from hydrogen; and X1 is selected from -NH-C(=O)-†, -C(=O)-NH-†, - -S(=O)2-NH-†, where † stands for place, where X1 is bound with R11; and, when R14 is H; R12is phenyl; and X1 is - C(=O)-NH-†, then R11 is not 1H-pyrazol-3-yl, possessing stimulating activity.

EFFECT: invention relates to pharmaceutical composition based on said compounds, method of treating subject, suffering from or having resistance to insulin, metabolic syndrome or diabetes, as well as to method of increasing sensitivity to insulin.

16 cl, 1 tbl, 24 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compounds can find application for preventing or treating cancer, lung cancer, non-small cells lung cancer, small-cell lung cancer, EML4-ALK hybrid polynucleotide-positive cancer, EML4-ALK hybrid polynucleotide-positive lung cancer or EML4-ALK hybrid polynucleotide-positive non-small cells lung cancer. In formula (I) -X-: group of formula , A represents chlorine, ethyl or isopropyl; R1 represents phenyl wherein carbon in the 4th position is substituted by the group -W-Y-Z, and carbon in the 3rd position can be substituted by a group specified in a group consisting of halogen, R00 and -O-R00; R00: lower alkyl which can be substituted by one or more halogen atoms; -W-: a bond, piperidine-1,4-diyl or piperazine-1,4-diyl; -Y- represents a bond; Z represents a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more substitutes R00; R2 represents (i) an optionally bridged saturated C3-10cycloalkyl which can be substituted by one or more groups specified in -N(lower alkyl)2, lower alkyl, -COO-lower alkyl, -OH, -COOH, -CONH-RZB and morpholinyl, or (ii) a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more groups specified in a group consisting of lower alkyl, -CO-lower alkyl, oxo, -CO-RZB and benzene; and RZB: phenyl which can be substituted by a group consisting of halogen and -O-lower alkyl; R3 represents -H.

EFFECT: invention refers to new compounds of formula or their pharmaceutically acceptable salts possessing the properties of a selective inhibitor of EML4-ALK hybrid protein kinase activity.

16 cl, 201 tbl, 582 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to methods of treating or relieving severity of disease in patient, where disease is selected from mucoviscidosis, hereditary emphysema, chronic obstructive pulmonary disease (COPD), "dry eye" disease. Methods include introduction of effective amount of N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or pharmaceutical composition, containing said compound, to patient.

EFFECT: treatment of relief of disease severity in patient, where disease is selected from mucoviscidosis, hereditary emphysema, chronic obstructive pulmonary disease (COPD), "dry eye" disease.

16 cl, 15 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula , wherein A means a six-merous aryl radical or a five-merous heteroaryl radical which contains one heteroatom specified in oxygen and sulphur; one or more hydrogen atoms in the above aryl or heteroaryl radicals can be substituted by substituting groups R1 which are independently specified in a group consisting of: F, Cl, Br, I, (C1-C10)-alkyl-, (C1-C10)-alkoxy-, -NR13R14; B means a radical with mono- or condensed bicyclic rings specified in a group consisting of: six-ten-merous aryl radicals, five-ten-merous heteroaryl radicals and nine-fourteen-merous cycloheteroalkylaryl radicals, wherein cycloheteroalkyl links can be saturated or partially unsaturated, while the heterocyclic groups can contain one or more heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, one or more hydrogen atoms in the radical groups B can be substituted by substituting groups R5 (as specified in the patent claim), L means a covalent bond, X means the group -O-, R2 is absent or means one or more substitutes specified in F and (C1-C4)-alkyl radical; R3 and R4 independently mean (C1-C10)-alkyl, (C3-C14)-cycloalkyl, (C4-C20)-cycloalkylalkyl, (C2-C19)-cycloheteroalkyl, (C3-C19)-cycloheteroalkylalkyl, (C6-C10)-aryl, (C7-C20)-arylalkyl, (C1-C9)-heteroaryl, (C2-C19)-heteroarylalkyl radicals, or R3 and R4 together with nitrogen attached whereto can form a four-ten-merous saturated, unsaturated or partially unsaturated heterocyclic compound which can additionally contain one or more heteroatoms among -O-, -S(O)n-, =N- and -NR8-; other radicals are such as specified in the patient claim. Also, the invention refers to using the compound of formula I for preparing a drug.

EFFECT: compounds of formula (I) as Na+/H+ metabolism inhibitors NHE3.

22 cl, 27 dwg, 1 tbl, 756 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of general formula (I) or pharmaceutically acceptable salts thereof, where Alk is an C1-C6alkyl group; G is C=O and Q is CR51R52 or NR51, where R51 and R52, being identical or different, independently denote H, C1-C6alkyl, optionally substituted with a substitute selected from a group comprising carboxy, phenoxy, benzyloxy, C1-C6alkoxy or hydroxy; C3-C6cycloalkylC1-C6alkyl; phenylC1-C6alkyl, optionally substituted with a halogen; phenylamidoC1-C6alkyl; phenylC1-C6alkylamidoC1-C6alkyl, optionally substituted with a C1-C6alkoxy group; or R51 and R52, together with a carbon atom with which they are bonded form a C=O or C2-C6alkenyl group, optionally substituted with a phenyl; M1 is CR49, where R49 is H; M2 is CR50, where R50 is H; R38 is H, C1-C6alkyl, substituted with a phenoxy group; C3-C6cycloalkylC1-C6alkyl; arylC1-C6alkyl, optionally substituted with 1 or 2 substitutes selected from a group comprising C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxycarbonyl, carboxyl, N-methylamido, hydroxy, C1-C6alkoxyC1-C6alkoxy, C1-C6alkylthio, C1-C6alkylsulphanyl, cyano, halogen, perfluoroC1-C6alkyl, nitro, formyl, hydroxyC1-C6alkyl and amino, wherein the aryl moiety is a phenyl or naphthyl; and heteroarylC1-C6alkyl, where the heteroaryl moiety is pyridinyl, optionally substituted with 1 or 2 groups selected from C1-C6alkoxy or hydroxyC1-C6alkyl, pyrazolyl or isoxazolyl, substitute with 1 or 2 C1-C6alkyl groups; R47 and R48 is C1-C6alkyl. The invention also relates to specific compounds, a method of reducing or weakening bitter taste, a composition of a food/non-food product or beverage or drug for reducing or lightening bitter taste and a method of producing a compound of formula (I).

EFFECT: obtaining novel compounds which are useful as bitter taste inhibitors or taste modulators.

37 cl, 6 dwg, 12 tbl, 186 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of organic chemistry, namely to compounds of the general formula I , and its pharmaceutically acceptable salts, where R1, R2 and R3 represent hydrogen, D, E, G, J and L represent CH; n equals to an integer number 1 or 2; W represents oxygen; R4 represents C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkenyl, where the said C1-6alkyl is possibly substituted with one substituent, independently selected from a group, consisting of hydrogen, C1-4alkyl, C3-6cycloalkyl and C3-6cycloalkenyl; Y represents carbonyl; R5 represents C1-6alkyl, C1-6alkoxy or C3-4heteroaryl, which represents a heterocyclic aromatic ring, containing 1-2 heteroatoms, selected from nitrogen and oxygen. The invention also relates to a pharmaceutical composition based on a formula I compound, application of the formula I compound and a method of prevention, treatment of alleviation of a disease, associated with abnormal angiogenesis.

EFFECT: obtained are novel compounds useful in treatment of diseases associated with unregulated angiogenesis, such as cancer, as well as skin and eye diseases.

13 cl, 3 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel fungicidally active 5-fluoropyrimidines of general formula I. In compounds of formula , R1 is -N(R3)R4; R2 is -OR21; R3 is: H; C1-C6-alkyl, optionally substituted with 1-3 groups R5; C2-C6-alkenyl, optionally substituted with 1-3 groups R5; a 5- or 6-member heteroaromatic cycle, selected from a group consisting of furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl; wherein each heteroaromatic cycle is optionally substituted with 1-3 R29 groups; 3H-isobenzofuran-1-oyl; -C(=O)R6; -C(=S)R6; -C(=S)NHR8; -(=O)N(R8)R10; -OR7; -P(O)(OR15)2; -S(O)2R8;-SR8; -Si(R8)3; -N(R9)R10; -(CHR24)mOR29 or -C(=NR16)SR16; where m equals an integer from 1 to 3; R4 is: H; C1-C6-alkyl, optionally substituted with 1-3 R5 groups; or -C(=O)R6; alternatively, R3 and R4 together can form: a 5- or 6-member saturated or unsaturated cycle containing 1-2 heteroatoms selected from N and O, where each cycle can be optionally substituted with 1-3 R11 groups; =C(R12)N(R13)R14 or =C(R15)OR15. The rest of the radicals are given in the claim.

EFFECT: obtaining novel fungicidally active 5-fluoropyrimidines of general formula I.

4 cl, 3 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) , where R1 and R2 have the following values: (i) R1 and R2 together form =O; (ii) R1 and R2 together with carbon atom, which they are bound with, form duoxacycloalkyl; R1 represents hydrogen or halogen; and R2 represents halogen; (iv) R1 represents C1-6alkyl, where alkyl is optionally substituted with cyano, -RxS(O)qRv or -RxNRyRz; and R2 represents hydrogen; (v) R1 represents -OR12 or -NR13R14; and R2 represents hydrogen, deutero or phenyl, which is optionally substituted with halogen; R3 represents hydrogen, halogen, C1-6alkyl, cyano, halogen C1-6alkyl, C3-10cycloalkyl or C1-6alkoxy; R4 and R5 represent hydrogen; R6 is independently selected from halogen, C1-6alkyl, halogenC1-6alkyl, -RxOR18 and -RxS(O)qRv; R7 independently represents halogen or -RxORw; R12 is selected from hydrogen and C1-6alkyl, R13 represents hydrogen; R14 is selected from hydrogen, C3-10cycloalkyl, -C(O)Rv and -C(O)ORw; R18 represents hydrogen, C1-6alkyl, or pyperidinyl, where R18 is optionally substituted with 1-3 Q1 groups, each Q1 is independenly selected from hydroxyl, C1-6alkoxy, C1-6alkoxycarbonyl, carboxyl and morpholinyl; Rx independently represents C1-6alkylene or simple bond; Rv and Rw represent hydrogen or C1-6alkyl; Ry and Rz represent hydrogen; n has value 0-4; p has value 0-5; and each q independently has value 0, 1 or 2. Invention also relates to compounds of formula (II) , where substituents have values, given in the invention formula, to pharmaceutical composition, possessing inhibiting activity with respect to JAK kinases, containing compounds of formula (I) or (II), methods of treating JAK-modulated disease, and application of compounds of formula (I) or (II).

EFFECT: compounds of formula (I) or (II) as inhibitors of JAK kinases.

32 cl, 6 dwg, 2 tbl, 84 ex

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