Novel bicyclic heterocyclic compound

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel compound of formula (1) or its pharmaceutically acceptable salt, possessing SNS inhibiting properties. In general formula R¹ represents (1) hydrogen atom, (2) halogen atom, (3) C_1-6alkyl group or (4) C_1-6halogenalkyl group ₍where R¹ can be present in any substitutable position of benzene or pyridine ring); L represents (1) simple bond, (2) -O- or (3) -CH₂O- (where L can be present in position 5 or 6 of condensed cycle); R² represents (1) C_6-10aryl group (C_6-10aryl group is optionally condensed with C_3-6cycloalkane), optionally substituted with substituent(s), X represents carbon atom or nitrogen atom. Other values of radicals are given in the invention formula.

EFFECT: obtaining compounds which can be used to prepare medication for treatment or prevention of such diseases as neuropathic pain, nociceptive pain, dysuria, disseminated sclerosis, etc.

19 cl, 47 tbl, 237 ex

The scope of the invention

The present invention relates to a medicinal product for the treatment or prophylaxis of a pathology in a General sense, involving SNS (sensory neuron-specific sodium channel), which includes a new connection with benzimidazole or imidazopyridine skeleton as bicyclic heterocycle or its pharmaceutically acceptable salt as an active ingredient. In particular, the present invention relates to a medicinal product for the treatment or prevention of diseases such as neuropathic pain, nociceptive pain, dysuria, multiple sclerosis and the like.

Background of the invention

In 1952, Hodgkin and Huxley showed that the main core of neural activity is Na channel, and then were developed blockers of Na channels as a means of complications or local anesthetics. In 1961 it was found that lidocaine, which is one of the blockers of Na channels, provides an analgesic effect, and began its clinical use as a tool in blood. However, since the Na channel is also present in tissues that are not related to the nervous system, such as muscle, heart and the like, remained a problem side effects during systemic administration.

With the development of molecular biology one for d is ugim were identified subtypes of Na channels and it is now known that the α subunit of Na channel, which forms a pore, which includes 10 types. Sensory neuron-specific sodium channel (sensory nerve-specific Na channel), i.e., SNS, is one of these α subunits of Na channels is tetrodotoxin (TTX)-resistant Na channel located in having a small diameter cavity (C fiber) dorsal root ganglion, involved in nerve perception, and which is also called SCN10A, PN3 or NaV1.8 (non-patent documents 1, 2). It was reported that mice with SNS-“knockout” insensitive to mechanical stimulation, and the introduction of antisense to SNS models of neuropathic pain or inflammatory pain reduces hypersensitivity and abnormal perception.

Therefore we think that the inhibitor SNS will provide therapeutic or prophylactic drug, demonstrating the analgesic effects of diseases such as neuropathic pain, nociceptive pain, and the like, which is accompanied by pain, numbness, burning sensation, aching pain and the like, in each case with the involvement of C fibers. In addition, since SNS is not expressed in tissues that are not related to the nervous system and the Central nervous system, a drug that selectively inhibits SNS are considered to be a medicinal product that does not have pobo the different effects originating from tissues that are not related to the nervous system, and Central nervous system.

In addition, when the disorder of urination, as it was found, frequent urination, which is the main symptom of this disorder, caused by excessive activity of C fibers; in other words, the dysfunction of the afferent sensory nerve pathways from the lower urinary tract is involved in overactive bladder and cystalgia, and here the suppression of C-fiber sensory nerve of the bladder is an effective (non-patent document 3). Therefore, a drug that inhibits SNS, mainly causing neutral activity C fiber is expected to be a therapeutic or prophylactic agent from urination disorders, which has a new point of action.

On the other hand, in a recent message has documented that SNS detected only in C fiber ectopiceski is expressed in cerebellar Purkinje cells in patients with multiple sclerosis and is involved in the occurrence of the abnormal pattern of inflammation in the cerebellum (non-patent document 4). Thus, it is expected that the inhibitor SNS will be the first therapeutic or prophylactic agent against induction of symptoms caused by abnormal inflammation associated the with SNS expression in cerebellar neurons, such as ataxia and the like, in multiple sclerosis.

The following shows the effective treatment of the above diseases in clinical practice.

(1) neuropathic pain

Neuropathic pain refers to pain, including spontaneous pain and chronic pain developing as a result of nerve injury or nerve stimulation, even when there is no injury and no inflammation of the tissue after complete recovery. Examples include neuralgia after surgery in the lumbar region, diabetic neuropathy, neuralgia after shingles, reflexivearcade dystrophy, phantom limb pains, spinal cord injuries, cancerous pain, at a later stage and prolonged postoperative pain. SPULS (non-steroidal anti-inflammatory drugs)such as aspirin and the like, completely ineffective against neuropathic pain, and opioids, such as morphine and the like, are problematic in terms of resistance to the drug and induction of physiological symptom.

Currently only present on the market of the medicinal product, which is claimed to be effective against neuropathic pain, is meksiletin used in diabetic neuropathy. Because meksiletin n which has selectivity for Na channel, although it provides an analgesic effect, there are concerns that it has side effects and the introduction in higher doses, as reported, is impossible. Some other drugs are clinically used as an auxiliary means. Their examples include antidepressants (sulpirid, trazodone, fluvoxamine, milnacipran), the agonist epinephrine (clonidine, dexmedetomidine), antagonists of the NMDA receptor (ketamine hydrochloride, dextromethorphan), an anti-anxiety (diazepam, lorazepam, etizolam, hydroxyzine hydrochloride), an anticonvulsant drug (carbamazepine, phenytoin, sodium valproate, zonisamide), calcium antagonist (nifedipine, verapamil hydrochloride, lomerizine hydrochloride) and the like, all of which are used as auxiliary means. Taking into account the foregoing, it is desirable to obtain a therapeutic tool, no side effects, originating from tissues that are not related to the nervous system or the Central nervous system and is especially effective against the pain.

(2) nociceptive pain

Nociceptive pain refers to pain caused by activation of nociceptor (Aδ, and C fibers) by mechanical, hyperthermia or chemical noxious stimulation results in tissue damage, etc. Nociceptor sensitize by endogenous chemical stimulat and (causing pain substance), such as serotonin, substance P, bradykinin, prostaglandin and histamine. Examples of nociceptive pain include back pain, abdominal pain and pain in rheumatoid arthritis or osteoarthritis. In clinical practice, the use of NCPLS (acetylsalicylic acid, acetaminophen, diclofenac sodium, indomethacin, movetalk, flurbiprofen, loxoprofen sodium, ampiroxicam), steroid drugs (prednisone, methylprednisolone, dexamethasone, betamethasone), PGE₁(prostaglandin E1 (alprostadil, lipo alprostadil, limaprost alprostadil) and PGI₂(beraprost sodium).

(3) dysuria (disorder urination)

Dysuria is a disease mainly manifested in the form of such basic symptoms as frequent urination, incontinence of urine, feeling of residual urine and painful urination. Currently, the primary method of drug treatment of overactive bladder involves the use of an inhibitor of muscarinic receptor, which inhibits parasimpaticescoe nerve pathways to the bladder. However, it also found its limit. It has been described that capsaicin and resinous toxin, which are stimulants vanilloideae receptor, specifically act on C fiber, inhibiting its function. However, so far not found a drug that is actuat on SNS, present in the C fiber.

(4) multiple sclerosis

Multiple sclerosis is one type of demyelinating disease, which demonstrates scattered foci of demyelination in the white matter of the Central nervous system with various old and new lesions. Lesions occur more frequently in the white matter of the lateral cerebral ventricular periphery of the ocular nerve, brain stem, spinal cord, etc. Histologically myelin sheath is destroyed, and the axon and nerve cell is not damaged. As clinical symptoms occur symptoms such as ocular neuritis, diplopia, violations of the movement of the eyeball, such as nystagmus, paralysis convulsive, painful tonic convulsive attack, the syndrome Lermitte, ataxia, logopedia, urine-rectal disorder and the like, in various combinations. Their etiology is unknown, although there have been suggestions that this is due to autoimmune disease, infection, etc. In real time is highly desirable effective prophylactic or therapeutic drug of multiple sclerosis.

Patent document 1 specified below, refers to the selective modulator CRF1 receptor and, in particular, describes a compound represented by the following formula (A) (Example 5, k). Connections covered in PA is entom document differ that contain amide bond to the methylene on the imidazole ring, and differ from the compounds of the present invention containing the amino group in the methylene on the imidazole ring. In addition, patent document 1 does not contain any descriptions, offering the present invention.

Patent document 2 specified below belongs to the inhibitor of Rho kinase and, in particular, describes a compound represented by the following formula (B) (Example 321). Compounds covered in the patent document does not contain the Deputy on the nitrogen atom of imidazole ring and differ from the compounds according to the present invention essentially contains a Deputy. In addition, patent document 2 does not contain any descriptions, offering the present invention.

The list of documents

Patent documents

Patent document 1: WO 02/28839

Patent document 2: WO 2009/79011

Non-patent documents

non-patent document 1: Nature 379: 257, 1996

non-patent document 2: Pain 78: 107, 1998

non-patent document 3: Urology 57: 116, 2001

non-patent document 4: Brain Research 959: 235, 2003

Brief description of the invention

The problems solved by the present invention

The present invention is the provision of medicinal cf is DSTV for the prevention or treatment of a pathology in a General sense, involving SNS, in particular diseases such as neuropathic pain, nociceptive pain, urination disorder, multiple sclerosis and the like.

Means of solving problems

The authors of the present invention conducted in-depth research, trying to solve the above task, and it was found that bicyclic compound containing an imidazole ring, or its pharmaceutically acceptable salt inhibited TTX-resistant Na channel in cells expressing human SNS gene, and it has the activity of inhibiting SNS and is useful as a therapeutic or prophylactic agent against diseases such as neuropathic pain, nociceptive pain, urination disorder, multiple sclerosis and the like, which led to the creation of the present invention.

Accordingly, the present invention provides the following.

[1] a compound represented by the following formula (1), or its pharmaceutically acceptable salt (hereinafter in some cases listed as “compound of the present invention”):

the compound represented by the formula

where

R¹represents a hydrogen atom, halogen atom, alkyl group containing from 1 to 6 carbon atoms, halogenation group containing from 1 to 6 atoms ug is erode, alkoxygroup containing from 1 to 6 carbon atoms, or halogenlampe containing from 1 to 6 carbon atoms (R¹may be present as a substituent of the benzene ring or pyridine ring at any substitutable position on the ring),

L represents a simple bond, -O - or-CH₂O- (L may be present as a substituent of the benzene ring or pyridine ring at any substitutable position on the ring),

R²represents a substituted or unsubstituted 6-10 membered aryl group or a substituted or unsubstituted 5-to 10-membered aromatic heterocyclic group,

X represents a carbon atom or a nitrogen atom,

R³represents a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, substituted or unsubstituted alkenylphenol group containing from 2 to 6 carbon atoms, substituted or unsubstituted alkylamino group containing from 2 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl group, a substituted or unsubstituted 4-8-membered cycloalkenyl group, a substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group or a substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group,

R⁴isone hydrogen atom, substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, or a substituted or unsubstituted 3-8-membered cycloalkyl group,

R^5aand R^5beach independently represent a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, or R⁴and R^5anot necessarily related to education, together with the nitrogen atom is linked to R⁴, 4-8-membered saturated nitrogen-containing aliphatic heterocycle (in this case, R^5brepresents a hydrogen atom),

R⁶and R⁷each independently represent a hydrogen atom, substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, halogenation group containing from 1 to 6 carbon atoms, substituted or unsubstituted alkenylphenol group containing from 2 to 6 carbon atoms, substituted or unsubstituted alkylamino group containing from 2 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl group, a substituted or unsubstituted 4-8-membered cycloalkenyl group, a substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group, substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group, substituted or unsubstituted 6-10 membered aryl which the group or substituted or unsubstituted 5-to 10-membered aromatic heterocyclic group, or R⁶and R⁷not necessarily related to education, together with the nitrogen atom to which they are attached, a substituted or unsubstituted 4-8-membered saturated nitrogen-containing aliphatic heterocycle or substituted or unsubstituted 5-to 10-membered unsaturated nitrogen-containing aliphatic heterocycle (saturated or unsaturated nitrogen-containing aliphatic heterocycle contains from 0 to 2 oxygen atoms, 0 to 2 sulfur atoms and 1 to 3 nitrogen atoms) (hereinafter in some cases listed as “compound (1)”) or its pharmaceutically acceptable salt;

[2] the compound according to item [1], which is represented by the following formula (2):

where R¹, R², R³, R⁴, R^5a, R^5b, R⁶, R⁷, L and X have the meanings defined in paragraph [1] (hereinafter, in some cases listed as “compound (2)”), or its pharmaceutically acceptable salt;

[3] the compound according to item [1], which is represented by the following formula (3):

where R¹, R², R³, R⁴, R^5a, R^5b, R⁶, R⁷, L and X have the meanings defined in [1] (hereinafter, in some cases listed as “compound (3)”), or its pharmaceutically acceptable salt;

[4] the compound according to any one of paragraphs [1]-[3], where the R ²represents a substituted or unsubstituted phenyl group, or its pharmaceutically acceptable salt;

[5] the compound according to any one of paragraphs [1]-[4], where R³represents a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl group, a substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group or a substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group, or its pharmaceutically acceptable salt;

[6] the compound according to any one of paragraphs [1]-[5], where R⁶and R⁷each independently represent a hydrogen atom, substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, halogenation group containing from 1 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl group, a substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group or a substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group, or R⁶and R⁷not necessarily related to education, together with the nitrogen atom to which they are attached, a substituted or unsubstituted 4-8-membered saturated nitrogen-containing aliphatic Goethe is of ozila or substituted or unsubstituted 5-to 10-membered unsaturated nitrogen-containing aliphatic heterocycle (saturated or unsaturated nitrogen-containing aliphatic heterocycle contains from 0 to 2 oxygen atoms, from 0 to 2 sulfur atoms and 1 to 3 nitrogen atoms), or its pharmaceutically acceptable salt;

[7] the compound according to any one of paragraphs [1]-[6], where R⁴represents a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, or its pharmaceutically acceptable salt;

[8] the compound according to any one of paragraphs [1]-[7], where R^5aand R^5beach independently represent a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, or its pharmaceutically acceptable salt;

[9] the compound according to any one of paragraphs [1]-[8], where X represents a carbon atom, or its pharmaceutically acceptable salt;

[10] the compound according to any of items [1]to[9], where R¹represents a hydrogen atom or halogen atom, or its pharmaceutically acceptable salt;

[11] the compound according to any one of paragraphs [1]-[10], where L represents a simple bond, or its pharmaceutically acceptable salt;

[12] the compound according to any one of paragraphs [1]-[10], where L represents-O-, or its pharmaceutically acceptable salt;

[13] the compound according to any one of paragraphs [1]-[10], where L represents-CH₂O-, or its pharmaceutically acceptable salt;

[14] N²-{[1-(2-ataxite is)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}glycinamide,

N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-2-methylalanine,

N²-{[1-cyclopropyl-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-cyclobutyl-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(4-chlorophenoxy)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(4-pertenece)-1-(2-hydroxy-2-methylpropyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(4-pertenece)-1-(3-methoxypropyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(2-chloro-4-pertenece)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-ethyl-6-(4-methylphenoxy)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(2,4-divergence)-1-(2-hydroxy-2-methylpropyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-(2-ethoxyethyl)-5-fluoro-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-ethyl-5-fluoro-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-(3-methoxypropyl)-6-(4-methylphenoxy)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(4-methylphenoxy)-1-(tetrahydro-2H-Piran-4-yl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[5-chloro-1-(2-ethoxyethyl)-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate or

N -{[5-chloro-6-(3,4-differenl)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

or pharmaceutically acceptable salt of such a compound;

[15] drug comprising the compound according to any one of paragraphs [1]-[14] or its pharmaceutically acceptable salt as an active ingredient;

[16] the drug according to item [15], which is an agent for the prevention or treatment of neuropathic pain, nociceptive pain, urination disorders or multiple sclerosis;

[17] the inhibitor SNS, including a connection according to any of items [1]to[14] or its pharmaceutically acceptable salt as an active ingredient;

[18] the pharmaceutical composition comprising the compound according to any one of paragraphs [1]-[14] or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

The effect of the present invention

The present invention provides an inhibitor SNS, including new bicyclic compound or its pharmaceutically acceptable salt. Inhibitor SNS according to the present invention is useful as a drug for the treatment or prophylaxis of a pathology in a General sense, involving SNS, and, in particular, is applicable for patients with neuropathic pain, nociceptive pain, resstr Istvan urination, multiple sclerosis, etc.

Description of variants of the incarnation

In the present description, examples of the “halogen atom” include fluorine atom, chlorine atom, bromine atom and iodine atom.

“Alkyl group” means a linear or branched alkyl group containing from 1 to 6 carbon atoms, and specific examples include methyl group, ethyl group, through the group (1-through group, isopropyl group, 2-through the group), boutelou group (1-boutelou group), second-boutelou group (2-boutelou group), isobutylene group (2-methyl-1-through the group), tert-boutelou group (2-methyl-2-through the group), pentelow group (1-pentelow group), hexoloy group (1-hexoloy group) and the like. The alkyl group preferably represents an alkyl group containing from 1 to 4 carbon atoms.

“Halogenation group” means a linear or branched alkyl group containing from 1 to 6 carbon atoms, which is substituted by the same or different from each other by 1-5 halogen atoms, and specific examples include triptorelin group, 2,2-deperately group, 2,2,2-triptorelin group, 2-chloraniline group, panafcortelone group, 3,3,3-triptorelin group and the like. Halogenation group preferably represents halogenating group and Kilroy group, containing from 1 to 4 carbon atoms.

“Alchemilla group” means a linear or branched alkenylphenol group containing from 2 to 6 carbon atoms, and specific examples include vinyl group, 1-propenyloxy group, 2-propenyloxy group, 1-methylvinyl group, 1-butenyloxy group, 1-ethylvinyl group, 1-methyl-2-propenyloxy group, 2-butenyloxy group, 3-butenyloxy group, 2-methyl-1-propenyloxy group, 2-methyl-2-propenyloxy group, 1-pentanediol group, 1-hexenyl group and the like. Alchemilla group preferably represents alkenylphenol group containing from 2 to 4 carbon atoms.

“Alchemilla group” means a linear or branched alkylamino group containing from 2 to 6 carbon atoms, and specific examples include etinilnoy group, 1-propenyloxy group, 2-propenyloxy group, 1-butenyloxy group, 1-methyl-2-propenyloxy group, 3-butenyloxy group, 1-pantanillo group, 1-hexylamino group and the like. Alchemilla group preferably represents alkylamino group containing from 2 to 4 carbon atoms.

“Alkoxygroup” means a linear or branched alkoxygroup containing from 1 to 6 carbon atoms, and specific examples include a methoxy group, ethoxypropan, propoxylate, 1-methylethoxy, butoxypropyl, 1 methylpropan is a group, 2-methylpropoxy, 1,1-dimethylaminopropyl, pentyloxy, hexyloxy and the like. Alkoxygroup preferably represents alkoxygroup containing from 1 to 4 carbon atoms.

“Halogenlampe” means a linear or branched alkoxygroup containing from 1 to 6 carbon atoms, which is substituted by the same or different from each other by 1-5 halogen atoms, and specific examples include cryptometer, 2,2-dipterocarp, 2,2,2-triptracker, 2-chlorethoxyfos, pentafluoropropyl, 3,3,3-cryptocracy and the like. Halogenlampe preferably represents halogenlampe containing from 1 to 4 carbon atoms.

“Cycloalkyl group” means a 3 to 8-membered monocyclic or bicyclic cycloalkyl group, and specific examples include cyclopropyl group, cyclobutyl group, cyclopentyl group, tsiklogeksilnogo group, cycloheptyl group, cyclooctyl group and the like. Cycloalkyl group preferably is a 4-6-membered cycloalkyl group.

“Cycloalkenyl group” means a 4-to 8-membered monocyclic or bicyclic cycloalkenyl group, and specific examples include cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, qi is leptanillinae group and cyclooctyl group. The position of the double bond in the ring is not specifically limited.

Cycloalkenyl group preferably represents a 5 - or 6-membered cycloalkenyl group.

“Saturated aliphatic heterocyclic group” means a 4-to 8-membered monocyclic or bicyclic saturated aliphatic heterocyclic group containing 1 to 3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom (provided that the number of oxygen atoms and sulfur atoms contained in the saturated aliphatic heterocycle is for each kind of atoms to 2). The position of the heteroatom is not specifically limited, provided that the saturated aliphatic heterocyclic group is chemically stable. Specific examples include azetidinol group, pyrrolidinyl group, piperidino group, piperidino, piperazinilnom group, sepanlou group, atenilol group, tetrahydrofuryl group, tetrahydrocannibinol group, tetrahydropyranyloxy group, morpholinyl group, morpholinopropan, thiomorpholine group, 1,4-dioxolo group, 1,2,5-thiadiazolidine group, 1,4-occasianally group, 1,4-diazepino group and the like.

“Unsaturated aliphatic heterocyclic group” means a 5-10 membered monocyclic or bicyclic of nenasi the military aliphatic heterocyclic group, containing from 1 to 3 double bonds and 1 to 3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom (provided that the number of oxygen atoms and sulfur atoms contained in unsaturated aliphatic heterocycle, is for each kind of atoms to 2). The position of the heteroatom double bond is not specifically limited, provided that the unsaturated aliphatic heterocyclic group is chemically stable. Specific examples include pyrrolidino group, imidazolidinyl group, tetrahydroisoquinoline group and the like, and preferable are 2-pyrrolidinone group and 2-imidazolidinone group.

“Saturated nitrogen-containing aliphatic heterocycle” means a 4-to 8-membered monocyclic or bicyclic saturated aliphatic heterocycle containing at least one nitrogen atom and optionally additionally containing from 1 to 3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom (provided that the number of oxygen atoms and sulfur atoms contained in the saturated aliphatic heterocycle is for each kind of atoms to 2). The position of the heteroatom is not specifically limited, provided that the saturated nitrogen-containing aliphatic heterocycle is chemically stable. Specific examples include azetidinone number of the TSO, pyrolidine ring, imidazolidine ring, pyrazolidine ring, piperidine ring, pieperazinove ring, asianave ring, isakanova ring, morpholine ring, thiomorpholine ring, oxazolidine ring, thiazolidine ring and the like.

“Unsaturated nitrogen-containing aliphatic heterocycle” means a 4-to 8-membered monocyclic or bicyclic unsaturated aliphatic heterocycle containing at least one nitrogen atom and optionally additionally containing from 1 to 3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom (provided that the number of oxygen atoms and sulfur atoms contained in unsaturated aliphatic heterocycle, is for each kind of atoms to 2). The position of the heteroatom is not specifically limited, provided that the unsaturated nitrogen-containing aliphatic heterocycle is chemically stable. Specific examples include pyrrolinone ring, piperidine ring, imidazoline ring, pyrazoline ring, oxazolinone ring, thiazoline ring, tetrahydroquinoline ring, tetrahydroisoquinoline ring and the like.

“Aryl group” means a 6-10-membered monocyclic or bicyclic aryl group, and specific examples include phenyl group, 1-naftalina group, 2-naftalina gr the foam and the like.

“Aromatic heterocyclic group” means a 5-10 membered monocyclic or bicyclic aromatic heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom (provided that the number of oxygen atoms and sulfur atoms contained in the aromatic heterocyclic group is for each kind of atoms to 2). The position of the heteroatom is not specifically limited, provided that the aromatic heterocyclic group is chemically stable. Specific examples include follow group, thienyl group, pyrrolidino group, oxazolidinyl group, isoxazolyl group, thiazolidine group, isothiazolinone group, imidazolidinyl group, pyrazolidine group, foratenolol group, oxadiazolyl group, triazolyl group, pyridyloxy group, pyrimidinyl group, personilnya group, indolenine group, pinolillo group, izohinolinove group, chinazolinei group, imidazo[2,1-b][1,3]thiazolidine group and the like.

“Allylthiourea” means a linear or branched allylthiourea containing from 1 to 6 carbon atoms, and specific examples include metalcorp, ethylthiourea, PropertyGroup, 1-metilethylchlorophos, butylthiourea, 1-methylpropyloxy, 2-methylpropionate, 1,1-DIMET is latitiude, intelligroup, vexillographer and the like. Allylthiourea preferably represents allylthiourea containing from 1 to 4 carbon atoms.

Examples of alkyl in “alkylcarboxylic group” include groups similar to certain higher alkyl group. Preferred examples alkylcarboxylic group include acetyl group, propionyl group, butyryloxy group and the like.

“Alkylcarboxylic” means a group where the oxygen atom is linked to the carbonyl carbon of the above “alkylcarboxylic group”.

Examples of alkyl in “alkylsulfonyl group” include groups similar to defined above “alkyl group”. Preferred examples alkylsulfonyl groups include methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group and the like.

Examples of alkoxy in “alkoxycarbonyl group” include groups similar to defined above, “alkoxygroup”. Preferred examples alkoxycarbonyl groups include methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group, tert-butoxycarbonyl group and the like.

Examples of the alkyl group in the “amino group, optionally substituted by one alkyl group or the same or different from each drugabuse alkyl group, “carbamoyl group, optionally substituted by one alkyl group or the same or different from each other, the two alkyl groups” and “sulfamoyl group, optionally substituted by one alkyl group or the same or different from each other, the two alkyl groups include groups similar to defined above “alkyl group”.

Preferred examples of “amino group, optionally substituted by one alkyl group or the same or different from each other, the two alkyl groups” include methylaminopropyl, ethylamino, propylamino, dimethylaminopropyl, diethylaminopropyl, methylethylamine and the like.

Preferred examples of “carbamoyl group, optionally substituted by one alkyl group or the same or different from each other, the two alkyl groups” include methylcarbamoyl group, ethylcarbitol group, profilirovannuju group, isopropylcarbamate group, dimethylcarbamoyl group, diethylcarbamoyl group, methylethylcarbinol group and the like.

Preferred examples of “sulfamoyl group, optionally substituted by one alkyl group or the same or different from each other, the two alkyl groups” include methylsulfonyl group, ethylsulfate the optimum group, propylsulfonyl group, dimethylsulphamoyl group, diethylcarbamoyl group, methylaminoethanol group and the like.

Examples of “alkoxycarbonyl group” in the “amidinopropane, optionally substituted one alkoxycarbonyl group or the same or different from each other two alkoxycarbonyl groups include groups similar to defined above, “alkoxycarbonyl group”. Preferred examples of “amidinopropane, optionally substituted one alkoxycarbonyl group or the same or different from each other two alkoxycarbonyl groups” include methoxycarbonylamino, ethoxycarbonylmethoxy, propoxycarbonylphenoxide and the like.

The aryl group in the “alloctype”, “arylcarboxylic group” and “arylsulfonyl group” shall have the meaning given for the above-mentioned “aryl group”.

Aromatic heterocyclic group in the aromatic heterocyclisation”, “aromatic heterocalixarenes group” and “aromatic heterocyclisation group” shall have the meaning given for the above-mentioned “aromatic heterocyclic group”.

Deputy for the “alkyl group”, “alkenylphenol group” and “alkenylphenol group selected from the group comprising the decree is installed next (i)-(v), and can be the same or different from each other deputies:

(i) a halogen atom, hydroxyl group, carboxyl group and cyano;

(ii) substituted or unsubstituted amino group, substituted or unsubstituted carnemolla group and a substituted or unsubstituted Altamarena group;

(iii) alkoxygroup, halogenlampe, alkylcarboxylic group, alkylcarboxylic, alkoxycarbonyl group, allylthiourea and alkylsulfonyl group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, amino group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, alkoxygroup, halogenlampe, alkoxycarbonyl group, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group];

(iv) cycloalkyl group, cycloalkenyl the group and saturated or unsaturated aliphatic heterocyclic group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, carbonyl group, tocography, amino group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, carbamoyl group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, alkoxygroup, halogenlampe, optionally substituted alkoxycarbonyl group, optionally substituted alkylcarboxylic group, optionally substituted alkylsulfonyl group, optionally substituted alkyl groups, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for alkoxycarbonyl group, alkylcarboxylic group, alkylsulfonyl group and alkyl group include halogen atom, hydroxyl group, carboxyl group, alkoxygroup, halogenlampe and karbamoilnuyu group. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, Alcock carbonyloxy group, the nitrogroup, cyano and karbamoilnuyu group];

(v) aryl group, aromatic heterocyclic group, alloctype, aromatic heterotardigrada, arylcarbamoyl group, an aromatic geterotsiklicheskikh group, arylsulfonyl group and aromatic heterocyclisation group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl group, substituted or unsubstituted sulfamoyl group, alkoxygroup, halogenlampe, alkoxycarbonyl group, optionally substituted alkyl groups, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for the alkyl group include halogen atom, hydroxyl group, carboxyl group, alkoxygroup and halogenlampe. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group].

Deputy for “cycloalkyl group”, “cycloalkenyl groups, saturated aliphatic heterocyclic groups, unsaturated aliphatic heterocyclic group, a saturated nitrogen-containing aliphatic heterocycle” and “unsaturated nitrogen-containing aliphatic heterocycle” represents one Deputy or the same or different from each other, two or more substituents, which are selected from the group comprising the following (vi)-(x):

(vi) a halogen atom, hydroxyl group, carboxyl group, cyano, oxoprop, tocograph and amidinopropane, optionally substituted one alkoxycarbonyl group or the same or different from each other two alkoxycarbonyl groups;

(vii) substituted or unsubstituted amino group, substituted or unsubstituted carnemolla group and a substituted or unsubstituted Altamarena group;

(viii) an alkyl group, halogenation group, alkoxygroup, halogenlampe, alkylcarboxylic group, alkylcarboxylic, alkoxycarbonyl group, allylthiourea and alkylsulfonyl group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, carbamoyl group, optional Zam is on one alkyl group or the same or different from each other by two alkyl groups, alkoxygroup, optionally substituted alkoxygroup(groups) and/or carbamoyl group(or groups), halogenlampe, allylthiourea, alkoxycarbonyl group, optionally substituted alloctype, optionally substituted aromatic geterotsiklicheskikh, optionally substituted aryl groups, optionally substituted aromatic heterocyclic group and optionally substituted amino. Examples of the substituent for alloctype, aromatic geterotsiklicheskikh, aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group. Examples of the substituent for the amino group include an optionally substituted alkyl group, optionally substituted alkylcarboxylic group, optionally substituted alkylsulfonyl group and karbamoilnuyu group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups. Examples of the substituent for the alkyl group in the alkyl group, alkylcarboxylic group, alkylsulfonyl group and carbamoyl group include a halogen atom, hydroximino group, carboxyl group, alkoxygroup, halogenlampe and karbamoilnuyu group];

(ix) cycloalkyl group, cycloalkenyl group and saturated or unsaturated aliphatic heterocyclic group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, carbonyl group, tocography, amino group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, alkoxygroup, halogenlampe, alkoxycarbonyl group, optionally substituted alkyl groups, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for the alkyl group include halogen atom, hydroxyl group, carboxyl group, alkoxygroup and halogenlampe. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group];

(x) aryl group, aromatic heterocyclic group, alloctype, aromatic g is eroticlingerie, arylcarbamoyl group, an aromatic geterotsiklicheskikh group, arylsulfonyl group and aromatic heterocyclisation group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, ceanography, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl group, substituted or unsubstituted sulfamoyl group, alkoxygroup, halogenlampe, alkoxycarbonyl group, optionally substituted alkyl groups, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for the alkyl group include halogen atom, hydroxyl group, carboxyl group, alkoxygroup and halogenlampe. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group].

Deputy for “phenyl group”, “aryl group” and “aromatic heterocyclic group” represents 1-5 substituents selected from GRU the dust, includes the following (xi)-(xv):

(xi) halogen atom, hydroxyl group, carboxyl group, cyano, a nitro-group, methylendioxy, atlantoxerus and -(CH₂)_n- (n is an integer having a value of from 3 to 5);

(xii) substituted or unsubstituted amino group, substituted or unsubstituted carnemolla group and a substituted or unsubstituted Altamarena group;

(xiii) an alkyl group, halogenation group, Alchemilla group, Alchemilla group, alkoxygroup, halogenlampe, alkylcarboxylic group, alkylcarboxylic, alkoxycarbonyl group, allylthiourea and alkylsulfonyl group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, amino group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, optionally substituted alkoxygroup, halogenlampe, alkoxycarbonyl group, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for alkoxygroup, aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl the th group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group];

(xiv) cycloalkyl group, cycloalkenyl group and saturated or unsaturated aliphatic heterocyclic group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, carbonyl group, tocography, amino group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, alkoxygroup, halogenlampe, alkoxycarbonyl group, optionally substituted alkyl groups, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for the alkyl group include halogen atom, hydroxyl group, carboxyl group, alkoxygroup and halogenlampe. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group];

(xv) aryl group is a, aromatic heterocyclic group, alloctype, aromatic heterotardigrada, arylcarbamoyl group, an aromatic geterotsiklicheskikh group, arylsulfonyl group and aromatic heterocyclisation group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl group, substituted or unsubstituted sulfamoyl group, alkoxygroup, halogenlampe, alkoxycarbonyl group, optionally substituted alkyl groups, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for the alkyl group include halogen atom, hydroxyl group, carboxyl group, alkoxygroup and halogenlampe. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group].

Deputy for the “amino group”, “carbamoyl group” and “sulfato Inoi group” represents one Deputy or the same or different from each other, two Deputy, selected from the group comprising the following (xvi)-(xviii):

(xvi) an alkyl group, halogenation group, Alchemilla group, Alchemilla group, alkylcarboxylic group, alkylsulfonyl group and alkoxycarbonyl group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, amino group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, carbamoyl group, alkoxygroup, halogenlampe, alkoxycarbonyl group, saturated or unsaturated aliphatic heterocyclic group, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group];

(xvii) cycloalkyl group, cycloalkenyl group, and saturated or unsaturated aliphatic heterocyclic group

[these groups are optionally substituted by one or more will replace the guides and selected from a halogen atom, hydroxyl group, carboxyl group, carbonyl group, tocography, amino group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, alkoxygroup, halogenlampe, alkoxycarbonyl group, optionally substituted alkyl groups, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for the alkyl group include halogen atom, hydroxyl group, carboxyl group, alkoxygroup and halogenlampe. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group];

(xviii) aryl group, aromatic heterocyclic group, arylcarbamoyl group, an aromatic geterotsiklicheskikh group, arylsulfonyl group and aromatic heterocyclisation group

[these groups are optionally substituted by one or more substituents selected from a halogen atom, hydroxyl group, carboxyl group, amino group, not battelino substituted by one alkyl group or the same or different from each other by two alkyl groups, carbamoyl group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, sulfamoyl group, optionally substituted by one alkyl group or the same or different from each other by two alkyl groups, alkoxygroup, halogenlampe, alkoxycarbonyl group, optionally substituted alkyl groups, optionally substituted aryl groups and optionally substituted aromatic heterocyclic group. Examples of the substituent for the alkyl group include halogen atom, hydroxyl group, carboxyl group, alkoxygroup and halogenlampe. Examples of the substituent for the aryl group and aromatic heterocyclic group include halogen atom, hydroxyl group, carboxyl group, alkyl group, halogenation group, alkoxygroup, halogenlampe, alkoxycarbonyl group, a nitrogroup, cyano and karbamoilnuyu group].

In addition, two Deputy for the “amino group”, “carbamoyl group” or “sulfamoyl groups” are not necessarily related to education, together with the adjacent nitrogen atom, 5-to 10-membered nitrogen-containing aliphatic heterocycle.

Examples of nitrogen-containing aliphatic heterocycle include pyrolidine ring, Piperi the new ring, asianova ring, isakanova ring, pieperazinove ring, morpholine ring, thiomorpholine ring and tetrahydroisoquinoline ring. In addition, nitrogen-containing aliphatic heterocycle optionally substituted by one or more substituents selected from a halogen, hydroxyl group, carboxyl group, optionally substituted alkyl groups, halogenoalkanes group, alkoxygroup and halogenlampe. Examples of the substituent for the alkyl group include halogen atom, hydroxyl group, carboxyl group, alkoxygroup, halogenlampe and karbamoilnuyu group.

In the compound of the present invention, represented by formula (1), each group preferably defined as follows.

R¹represents a hydrogen atom, halogen atom, alkyl group containing from 1 to 6 carbon atoms, halogenation group containing from 1 to 6 carbon atoms, alkoxygroup containing from 1 to 6 carbon atoms, or halogenlampe containing from 1 to 6 carbon atoms, preferably represents a hydrogen atom, halogen atom, alkyl group containing from 1 to 6 carbon atoms or halogenation group containing from 1 to 6 carbon atoms, more preferably a hydrogen atom, halogen atom or alkyl group containing from 1 to d is 6 atoms carbon more preferably a hydrogen atom or a halogen atom, particularly preferably a hydrogen atom. R¹may be present on the benzene ring or pyridine ring at any substitutable position.

Specific examples of R¹include a hydrogen atom, fluorine atom, chlorine atom, methyl group, ethyl group, through the group, triptorelin group and the like. Of them, preferred are a hydrogen atom, fluorine atom and chlorine atom, and more preferred is a hydrogen atom.

L represents a simple bond, -O - or-CH₂O-, preferably a simple bond or-O-, more preferably-O-. L may be present on the benzene ring or pyridine ring at any substitutable position. When L represents-CH₂O-, an oxygen atom, a group-CH₂O - linked with the benzene ring or pyridine ring, and a methylene chain is associated with R².

R²represents a substituted or unsubstituted 6-10 membered aryl group or a substituted or unsubstituted 5-to 10-membered aromatic heterocyclic group, preferably a substituted or unsubstituted 6-10 membered aryl group, more preferably a substituted or unsubstituted phenyl group.

Preferred examples of the substituent aryl group or aromatic heterocyclic group for R² include a halogen atom, substituted or unsubstituted alkyl group (preferably unsubstituted alkyl group containing from 1 to 6 carbon atoms), halogenating group (preferably halogenating group containing from 1 to 6 carbon atoms), alkoxygroup (preferably alkoxygroup containing from 1 to 6 carbon atoms), halogenlampe (preferably halogenlampe containing from 1 to 6 carbon atoms), cyano and the like, in particular a fluorine atom, a chlorine atom, methyl group, ethyl group, isopropyl group, tert-boutelou group, triptorelin group, cryptometer, a methoxy group, ethoxypropan, a cyano and similar. Of them, preferred are a fluorine atom, a methyl group and tripterocarpa.

Specific examples of the substituted or unsubstituted aryl group for R²include a phenyl group and phenyl group, substituted preferable Deputy(deputies) for the above-described aryl group, and the like.

Specific examples of the aromatic heterocyclic group for R²include pyridyloxy group, follow group, thienyl group, pyrimidinyl group, personilnya group and the like. Of them, preferred are Peregrina group and furilla group.

R³represents a substituted or n is substituted alkyl group, containing from 1 to 6 carbon atoms, substituted or unsubstituted alkenylphenol group containing from 2 to 6 carbon atoms, substituted or unsubstituted alkylamino group containing from 2 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl group, a substituted or unsubstituted 4-8-membered cycloalkenyl group, a substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group or a substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group, preferably a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl group, substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group or a substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group, more preferably a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl group or a substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group, more preferably a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, or a substituted or unsubstituted 3-8-membered cycloalkyl.

Preferred examples of the substituent for the alkyl group for R³include a hydroxyl group, alkoxygroup (preferably alkoxygroup containing from 1 to 6 carbon atoms), 4-8-membered saturated aliphatic heterocyclic group and the like, in particular a hydroxyl group, a methoxy group, ethoxypropan, isopropoxy, tetrahydrofuryl group, tetrahydropyranyl group and the like.

Preferred examples of the substituent for the saturated aliphatic heterocyclic group for R³include alkylcarboxylic group, alkoxycarbonyl group, alkylsulfonyl group, mono-alkylcarboxylic group (alkyl group preferably contains from 1 to 6 carbon atoms) and the like, in particular acetyl group, tert-butoxycarbonyl group, methylsulfonyl group, isopropylcarbamate group and the like.

Specific examples of R³include ethyl group, isopropyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, methoxyamino group, ethoxyethylene group, isopropoxyaniline group, hydroxyethylene group, methoxypropyl group, ethoxypropanol group, hydroxypropyl group, tetrahydropyranyloxy group, tetrahydrofuryl group, 2,2-dimethyl-2-hydroxyethylene group, tet is hydrodynamically group, tetrahydropyrimidine group, 4-piperidino group, 1-(tert-butoxycarbonyl)piperidine-4-ilen group, 1-isopropylcarbodiimide-4-ilen group, 1-acetylpiperidine-4-ilen group, 1-methylsulfonylmethane-4-ilen group and the like. More preferably R³represents cyclobutyl group, 2-ethoxyethylene group or ethyl group.

R⁴represents a hydrogen atom, substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, or a substituted or unsubstituted 3-8-membered cycloalkyl group, preferably a hydrogen atom, or substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, more preferably a hydrogen atom.

Preferred examples of the substituent for the alkyl group and cycloalkyl group for R⁴include halogen atom, hydroxyl group, alkoxygroup (preferably alkoxygroup containing from 1 to 6 carbon atoms), 4-8-membered saturated aliphatic heterocyclic group and the like, in particular a fluorine atom, a chlorine atom, a hydroxyl group, a methoxy group, ethoxypropan, tetrahydrofuryl group, tetrahydropyranyl group and the like.

Specific examples of R⁴include a hydrogen atom, methyl group, cyclopropyl group and the like. Of them predpochtitel the YMI are a hydrogen atom and a methyl group, and more preferred is a hydrogen atom.

R^5aand R^5beach independently represent a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, or R⁴and R^5anot necessarily related to education, together with the nitrogen atom is linked to R⁴, 4-8-membered saturated nitrogen-containing aliphatic heterocycle (in this case, R^5brepresents a hydrogen atom), preferably each independently represents a hydrogen atom, or substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms. Preferred examples of the substituent for the alkyl group for R^5aor R^5binclude halogen atom, hydroxyl group, alkoxygroup (preferably alkoxygroup containing from 1 to 6 carbon atoms), 4-8-membered saturated aliphatic heterocyclic group and the like, in particular a fluorine atom, a chlorine atom, a hydroxyl group, a methoxy group, ethoxypropan, tetrahydrofuryl group, tetrahydropyranyl group and the like.

Specific examples of R^5aand R^5binclude, each independently, a hydrogen atom, methyl group, ethyl group and isopropyl group (preferably R^5arepresents a hydrogen atom, methyl group, ethyl group or isopropyl group, and R^5brepresents METI is inuu group, ethyl group or isopropyl group). Of them, preferred are a hydrogen atom and a methyl group (preferably R^5arepresents a hydrogen atom, and R^5brepresents a methyl group).

When R^5aand R^5bare different from each other, the carbon atom with which they are associated, is an asymmetric carbon atom, and spatial configuration preferably is an S-configuration, taking into account aspects such as the availability of the starting materials.

Specific examples 4-8-membered saturated nitrogen-containing aliphatic heterocycle formed by R⁴and R^5athat are associated with each other, together with the nitrogen atom is linked to R⁴include azetidinone ring, pyrolidine ring, piperidine ring and the like. Of them pyrolidine ring is preferred.

R⁶and R⁷each independently represent a hydrogen atom, substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, halogenation group containing from 1 to 6 carbon atoms, substituted or unsubstituted alkenylphenol group containing from 2 to 6 carbon atoms, substituted or unsubstituted alkylamino group containing from 2 to 6 carbon atoms, substituted or unsubstituted 3-8-members of the ing cycloalkyl group, substituted or unsubstituted 4-8-membered cycloalkenyl group, a substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group, substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group, substituted or unsubstituted 6-10 membered aryl group or a substituted or unsubstituted 5-to 10-membered aromatic heterocyclic group, or R⁶and R⁷not necessarily related to education, together with the nitrogen atom to which they are attached, a substituted or unsubstituted 4-8-membered saturated nitrogen-containing aliphatic heterocycle or substituted or unsubstituted 5-to 10-membered unsaturated nitrogen-containing aliphatic heterocycle (saturated or unsaturated nitrogen-containing aliphatic heterocycle contains from 0 to 2 oxygen atoms, 0 to 2 sulfur atoms and 1 to 3 nitrogen atoms), preferably each independently represents a hydrogen atom, substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, halogenation group containing from 1 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl group, a substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group or a substituted or unsubstituted 5-to 10-membered unsaturated aliphatic, heterocyclic is a mini-group, more preferably each independently represents a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, more preferably a hydrogen atom.

Preferred examples of the substituent for the alkyl group for R⁶or R⁷include a hydroxyl group, alkoxygroup (preferably alkoxygroup containing from 1 to 6 carbon atoms), 4-8-membered saturated aliphatic heterocyclic group and the like, in particular a hydroxyl group, a methoxy group, ethoxypropan, tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group, piperidino, piperazinilnom group, morpholinopropan and the like. Specific examples of substituted alkyl groups for R⁶or R⁷include methoxyamino group, 2,2-dimethyl-2-hydroxyethylene group, morpholinoethyl group and the like.

Preferred specific examples of R⁶or R⁷include a hydrogen atom, methyl group, ethyl group, isopropyl group and the like. Of them, preferred are a hydrogen atom and a methyl group, and more preferred is a hydrogen atom.

Specific examples of the substituted or unsubstituted 4-8-membered saturated nitrogen-containing aliphatic heterocycle and to replace the military or unsubstituted 5-to 10-membered unsaturated nitrogen-containing aliphatic heterocycle, which formed R⁶and R⁷that are associated with each other, together with the nitrogen atom to which they relate, include morpholino ring, pyrolidine ring, piperidine ring, pieperazinove ring and the like. Of them, preferred are morpholino ring and pieperazinove ring.

Preferred examples of the substituent for the above saturated nitrogen-containing aliphatic heterocycle or unsaturated nitrogen-containing aliphatic heterocycle include oxoprop, cyano, halogenation group (preferably halogenating group containing from 1 to 6 carbon atoms) and the like. Of them, preferred are oxoprop, cyano and triptorelin group.

Preferred examples of the compound (1) include the following compounds and their pharmaceutically acceptable salts.

Preferred variants of the embodiment includes the connection, where

R¹represents a hydrogen atom or halogen atom,

L represents a simple bond or-O-,

R²represents a substituted or unsubstituted phenyl group,

X represents a carbon atom,

R³represents a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl GRU is PU, substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group or a substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group,

R⁴represents a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms,

R^5aand R^5beach independently represent a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, and

R⁶and R⁷each independently represent a hydrogen atom, substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms, halogenation group containing from 1 to 6 carbon atoms, substituted or unsubstituted 3-8-membered cycloalkyl group, a substituted or unsubstituted 4-8-membered saturated aliphatic heterocyclic group or a substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group, or

R⁶and R⁷not necessarily related to education, together with the nitrogen atom to which they are attached, a substituted or unsubstituted 4-8-membered saturated nitrogen-containing aliphatic heterocycle or substituted or unsubstituted 5-to 10-membered unsaturated nitrogen-containing aliphatic heterocycle (saturated or unsaturated with the first nitrogen-containing aliphatic heterocycle contains from 0 to 2 oxygen atoms, from 0 to 2 sulfur atoms and 1 to 3 nitrogen atoms).

Other preferred variants of the embodiment includes the connection, where

R¹represents a hydrogen atom, halogen atom or alkyl group containing from 1 to 6 carbon atoms,

L represents a simple bond or-O-,

R²represents a substituted or unsubstituted 6-10 membered aryl group (Deputy preferably represents a halogen atom, an alkyl group containing from 1 to 6 carbon atoms or halogenlampe containing from 1 to 6 carbon atoms, more preferably a fluorine atom, a methyl group, or cryptometer),

X represents a carbon atom,

R³represents a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms (Deputy preferably represents a hydroxyl group, alkoxygroup containing from 1 to 6 carbon atoms, or 4 to 8-membered saturated aliphatic heterocyclic group, more preferably a hydroxyl group, a methoxy group, ethoxypropan, isopropoxy, tetrahydrofuryl group or tetrahydropyranyloxy group), substituted or unsubstituted 3-8-membered cycloalkyl group (preferably unsubstituted 3-8-membered cycloalkyl group), substituted or unsubstituted 4-8-membered the feast upon the percent aliphatic heterocyclic group (preferably unsubstituted 4-8-membered saturated aliphatic heterocyclic group or substituted or unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group (preferably unsubstituted 5-to 10-membered unsaturated aliphatic heterocyclic group),

R⁴represents a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms (preferably unsubstituted alkyl group containing from 1 to 6 carbon atoms),

R^5aand R^5beach independently represent a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms (preferably unsubstituted alkyl group containing from 1 to 6 carbon atoms), and

R⁶and R⁷each independently represent a hydrogen atom or a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms (preferably unsubstituted alkyl group containing from 1 to 6 carbon atoms).

Of these compounds, which

R¹represents a hydrogen atom or halogen atom,

L represents a simple bond or-O-,

R²represents a substituted or unsubstituted phenyl group (Deputy preferably represents a halogen atom, an alkyl group containing from 1 to 6 carbon atoms, or halogenlampe containing from 1 to 6 carbon atoms, more preferably a fluorine atom, a methyl group, or cryptometer),

X PR is dstanley a carbon atom,

R³represents a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms (Deputy preferably represents a hydroxyl group, alkoxygroup containing from 1 to 6 carbon atoms, or 4 to 8-membered saturated aliphatic heterocyclic group, more preferably a hydroxyl group, a methoxy group, ethoxypropan, isopropoxy, tetrahydrofuryl group or tetrahydropyranyloxy group), or substituted or unsubstituted 3-8-membered cycloalkyl group (preferably unsubstituted 3-8-membered cycloalkyl group)

R⁴represents a hydrogen atom or methyl group,

R^5aand R^5beach independently represent a hydrogen atom, methyl group, ethyl group or isopropyl group (preferably R^5arepresents a hydrogen atom, methyl group, ethyl group or isopropyl group, and R^5brepresents a methyl group, ethyl group or isopropyl group), and

R⁶and R⁷represents a hydrogen atom,

is preferred, and

connection, where

R¹represents a hydrogen atom,

L represents-O-,

R²represents a substituted or unsubstituted phenyl group (Deputy predpochtitel what about represents a halogen atom, alkyl group containing from 1 to 6 carbon atoms, or halogenlampe containing from 1 to 6 carbon atoms, more preferably a fluorine atom, a methyl group, or cryptometer),

X represents a carbon atom,

R³represents a substituted or unsubstituted alkyl group containing from 1 to 6 carbon atoms (Deputy preferably represents a hydroxyl group, alkoxygroup containing from 1 to 6 carbon atoms, or 4 to 8-membered saturated aliphatic heterocyclic group, more preferably a hydroxyl group, a methoxy group, ethoxypropan, isopropoxy, tetrahydrofuryl group or tetrahydropyranyloxy group), or substituted or unsubstituted 3-8-membered cycloalkyl group (preferably unsubstituted 3-8-membered cycloalkyl group)

R⁴represents a hydrogen atom or methyl group,

R^5aand R^5beach independently represent a hydrogen atom or a methyl group (preferably R^5arepresents a hydrogen atom and R^5brepresents a methyl group), and

R⁶and R⁷represents a hydrogen atom,

is more preferred.

The compound of the present invention is preferably a compound (2), or the connection is giving (3), or its pharmaceutically acceptable salt, more preferably the compound (2) or its pharmaceutically acceptable salt.

Preferred specific examples include the following compounds and their pharmaceutically acceptable salts.

Specific examples include the connection, where

R¹represents a

(1) a hydrogen atom,

(2) a halogen atom (preferably fluorine atom, chlorine atom),

(3) C_1-6alkyl group (preferably methyl) or

(4) C_1-6halogenating group (preferably trifluoromethyl),

L represents a

(1) a simple link,

(2) -O - or

(3) -CH₂O-,

R²represents a

(1) C_6-10aryl group (C_6-10aryl group optionally is condensed with C_3-6cyclopropane) (preferably phenyl, indanyl, more preferably phenyl), optionally substituted by 1-3 substituents selected from the

(a) a halogen atom (preferably fluorine atom, chlorine atom),

(b) C_1-6alkyl group (preferably methyl, ethyl, isopropyl, tert-butyl),

(c) C_1-6halogenoalkanes group (preferably trifloromethyl),

(d) C_1-6alkoxygroup (preferably methoxy, ethoxy),

(e) C_1-6halogenlampe (preferably triptoreline) and

(f) ceanography or

(2) 5-10-membered aromatic the Russian heterocyclic group (preferably 5 - or 6-membered aromatic heterocyclic group, more preferably pyridyl, furil),

X represents a carbon atom or a nitrogen atom,

R³represents a

(1) C_1-6alkyl group (preferably methyl, ethyl, propyl, isopropyl, isobutyl), optionally substituted by 1-3 substituents selected from the

(a) C_1-6alkoxygroup (preferably methoxy, ethoxy, isopropoxy),

(b) 4-to 8-membered saturated aliphatic heterocyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably of tetrahydropyranyl, tetrahydrofuryl), and

(c) a hydroxyl group,

(2) C_3-8cycloalkyl group (preferably cyclopropyl, cyclobutyl, cyclopentyl) or

(3) 4-to 8-membered saturated aliphatic heterocyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably tetrahydropyranyl, piperidyl), optionally substituted by 1-3 substituents selected from the

(a) C_1-6alkyl-carbonyl group (preferably acetyl),

(b) C_1-6alkoxy-carbonyl group (preferably tert-butoxycarbonyl),

(c) C_1-6alkylsulfonyl group (preferably methylsulphonyl), and

(d) carbamoyl group, optionally mono - or di-substituted C_1-6alkyl group(the group) (predpochtitelno isopropyl),

R⁴represents a

(1) a hydrogen atom, or

(2) C_1-6alkyl group (preferably methyl),

R^5aand R^5beach independently represent

(1) a hydrogen atom, or

(2) C_1-6alkyl group (preferably methyl, ethyl, isopropyl), or

R⁴and R^5anot necessarily related to education, together with the nitrogen atom is linked to R⁴, 4-8-membered saturated nitrogen-containing aliphatic heterocycle (preferably 5 - or 6-membered saturated nitrogen-containing aliphatic heterocycle, more preferably pyrrolidin) (R^5brepresents a hydrogen atom), and

R⁶and R⁷each independently represent

(1) a hydrogen atom, or

(2) C_1-6alkyl group (preferably ethyl, isobutyl), optionally substituted by 1-3 substituents selected from the

(a) a hydroxyl group,

(b) C_1-6alkoxygroup (preferably methoxy), and

(c) 4-to 8-membered saturated aliphatic heterocyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably of morpholinyl), or

R⁶and R⁷not necessarily related to education, together with the nitrogen atom to which they relate, 4-8-membered saturated nitrogen-containing aliphatic heterocycle (predpochtitelno 5 - or 6-membered saturated nitrogen-containing aliphatic heterocycle, more preferably the research, piperazine), optionally substituted by 1-3 substituents selected from the

(a) the carbonyl group,

(b) ceanography and

(c) C_1-6halogenoalkanes group (preferably trifluoromethyl).

Preferred specific examples include the connection, where

R¹represents a

(1) a hydrogen atom, or

(2) a halogen atom (preferably fluorine atom, chlorine atom),

L represents a

(1) a simple link or

(2) -O-,

R²represents a phenyl group, optionally substituted by 1-3 substituents selected from the

(a) a halogen atom (preferably fluorine atom, chlorine atom),

(b) C_1-6alkyl group (preferably methyl, ethyl, isopropyl, tert-butyl),

(c) C_1-6halogenoalkanes group (preferably trifloromethyl),

(d) C_1-6alkoxygroup (preferably methoxy, ethoxy),

(e) C_1-6halogenlampe (preferably triptoreline) and

(f) ceanography,

X represents a carbon atom,

R³represents a

(1) C_1-6alkyl group (preferably methyl, ethyl, propyl, isopropyl, isobutyl), optionally substituted by 1-3 substituents selected from the

(a) C_1-6alkoxygroup (preferably methoxy, ethoxy, isopropoxy),

(b) 4-to 8-membered saturated aliphatic gets acyclically group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably tetrahydropyranyl, tetrahydrofuryl), and

(c) a hydroxyl group,

(2) C_3-8cycloalkyl group (preferably cyclopropyl, cyclobutyl, cyclopentyl) or

(3) 4-to 8-membered saturated aliphatic heterocyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably tetrahydropyranyl, piperidyl), optionally substituted by 1-3 substituents selected from the

(a) C_1-6alkyl-carbonyl group (preferably acetyl),

(b) C_1-6alkoxy-carbonyl group (preferably tert-butoxycarbonyl),

(c) C_1-6alkylsulfonyl group (preferably methylsulfonyl) and

(d) carbamoyl group, optionally mono - or di-substituted C_1-6alkyl group(the group) (preferably isopropyl),

R⁴represents a

(1) a hydrogen atom, or

(2) C_1-6alkyl group (preferably methyl),

R^5aand R^5beach independently represent

(1) a hydrogen atom, or

(2) C_1-6alkyl group (preferably methyl, ethyl, isopropyl), and

R⁶and R⁷each independently represent

(1) a hydrogen atom, or

(2) C_1-6alkyl group (preferably ethyl, isobutyl), optionally substituted by 1-3 substituents, is selected from

(a) a hydroxyl group,

(b) C_1-6alkoxygroup (preferably methoxy), and

(c) 4-to 8-membered saturated aliphatic heterocyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably of morpholinyl), or

R⁶and R⁷not necessarily related to education, together with the nitrogen atom to which they relate, 4-8-membered saturated nitrogen-containing aliphatic heterocycle (preferably 5 - or 6-membered saturated nitrogen-containing aliphatic heterocycle, more preferably of the research, piperazine), optionally substituted by 1-3 substituents selected from the

(a) the carbonyl group,

(b) ceanography and

(c) C_1-6halogenoalkanes group (preferably trifloromethyl).

Other preferred specific examples include the connection, where

R¹represents a

(1) a hydrogen atom,

(2) a halogen atom (preferably fluorine atom, chlorine atom), or

(3) C_1-6alkyl group (preferably methyl),

L represents a

(1) a simple link or

(2) -O-,

R²represents a C_6-10aryl group (C_6-10aryl group optionally is condensed with C_3-6cyclopropane) (preferably phenyl, indanyl, more preferably phenyl), optional what about substituted by 1-3 substituents, selected from the

(a) a halogen atom (preferably fluorine atom, chlorine atom),

(b) C_1-6alkyl group (preferably methyl, ethyl, isopropyl, tert-butyl),

(c) C_1-6halogenoalkanes group (preferably trifloromethyl),

(d) C_1-6alkoxygroup (preferably methoxy, ethoxy),

(e) C_1-6halogenlampe (preferably triptoreline) and

(f) ceanography,

X represents a carbon atom,

R³represents a

(1) C_1-6alkyl group (preferably methyl, ethyl, propyl, isopropyl, isobutyl), optionally substituted by 1-3 substituents selected from the

(a) C_1-6alkoxygroup (preferably methoxy, ethoxy, isopropoxy),

(b) 4-to 8-membered saturated aliphatic heterocyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably of tetrahydropyranyl, tetrahydrofuryl), and

(c) a hydroxyl group,

(2) C_3-8cycloalkyl group (preferably cyclopropyl, cyclobutyl, cyclopentyl) or

(3) 4-to 8-membered saturated aliphatic heterocyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably tetrahydropyranyl, piperidyl), optionally substituted by 1-3 substituents, select the reference from the

(a) C_1-6alkyl-carbonyl group (preferably acetyl),

(b) C_1-6alkoxy-carbonyl group (preferably tert-butoxycarbonyl),

(c) C_1-6alkylsulfonyl group (preferably methylsulfonyl) and

(d) carbamoyl group, optionally mono - or di-substituted C_1-6alkyl group(the group) (preferably isopropyl),

R⁴represents a

(1) a hydrogen atom, or

(2) C_1-6alkyl group (preferably methyl),

R^5aand R^5beach independently represent

(1) a hydrogen atom, or

(2) C_1-6alkyl group (preferably methyl, ethyl, isopropyl), and

R⁶and R⁷each independently represent

(1) a hydrogen atom, or

(2) C_1-6alkyl group (preferably ethyl, isobutyl), optionally substituted by 1-3 substituents selected from the

(a) a hydroxyl group,

(b) C_1-6alkoxygroup (preferably methoxy), and

(c) 4-to 8-membered saturated aliphatic heterocyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably of morpholinyl).

Of these compounds, which

R¹represents a

(1) a hydrogen atom, or

(2) a halogen atom (preferably fluorine atom, chlorine atom),

L represents the oops

(1) a simple link or

(2) -O-,

R²represents a phenyl group optionally substituted by 1-3 substituents selected from the

(a) a halogen atom (preferably fluorine atom, chlorine atom),

(b) C_1-6alkyl group (preferably methyl, ethyl, isopropyl, tert-butyl),

(c) C_1-6halogenoalkanes group (preferably trifloromethyl),

(d) C_1-6alkoxygroup (preferably methoxy, ethoxy),

(e) C_1-6halogenlampe (preferably triptoreline) and

(f) ceanography,

X represents a carbon atom,

R³represents a

(1) C_1-6alkyl group (preferably methyl, ethyl, propyl, isopropyl, isobutyl), optionally substituted by 1-3 substituents selected from the

(a) C_1-6alkoxygroup (preferably methoxy, ethoxy, isopropoxy),

(b) 4-to 8-membered saturated aliphatic heterocyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably of tetrahydropyranyl, tetrahydrofuryl) and

(c) a hydroxyl group, or

(2) C_3-8cycloalkyl group (preferably cyclopropyl, cyclobutyl, cyclopentyl),

R⁴represents a hydrogen atom or methyl group,

R^5aand R^5beach independently represent seboyeta hydrogen, methyl group, ethyl group or isopropyl group (preferably R^5arepresents a hydrogen atom, methyl group, ethyl group or isopropyl group, and R^5brepresents a methyl group, ethyl group or isopropyl group), and

R⁶and R⁷represents a hydrogen atom,

is preferred, and

connection, where

R¹represents a hydrogen atom,

L represents-O-,

R²represents a phenyl group, optionally substituted by 1-3 substituents selected from the

(a) a halogen atom (preferably fluorine atom, chlorine atom),

(b) C_1-6alkyl group (preferably methyl, ethyl, isopropyl, tert-butyl),

(c) C_1-6halogenoalkanes group (preferably trifloromethyl),

(d) C_1-6alkoxygroup (preferably methoxy, ethoxy),

(e) C_1-6halogenlampe (preferably triptoreline) and

(f) ceanography,

X represents a carbon atom,

R³represents a

(1) C_1-6alkyl group (preferably methyl, ethyl, propyl, isopropyl, isobutyl), optionally substituted by 1-3 substituents selected from the

(a) C_1-6alkoxygroup (preferably methoxy, ethoxy, isopropoxy),

(b) 4-to 8-membered saturated aliphatic courtesans is a cyclic group (preferably 5 - or 6-membered saturated aliphatic heterocyclic group, more preferably tetrahydropyranyl, tetrahydrofuryl) and

(c) a hydroxyl group, or

(2) C_3-8cycloalkyl group (preferably cyclopropyl, cyclobutyl, cyclopentyl),

R⁴represents a hydrogen atom or methyl group, and

R^5aand R^5beach independently represent a hydrogen atom or a methyl group (preferably R^5arepresents a hydrogen atom, and R^5brepresents a methyl group), and

R⁶and R⁷represents a hydrogen atom,

is more preferred.

Other preferred specific examples include the

N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}glycinamide,

N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-2-methylalanine,

N²-{[1-cyclopropyl-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-cyclobutyl-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(4-chlorophenoxy)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(4-pertenece)-1-(2-hydroxy-2-methylpropyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate, N²-{[6-(4-pertenece)-1-(3-methoxypropyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-ethyl-6-(4-methylphenoxy)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(2,4-divergence)-1-(2-hydroxy-2-methylpropyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-(2-ethoxyethyl)-5-fluoro-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-ethyl-5-fluoro-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[1-(3-methoxypropyl)-6-(4-methylphenoxy)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[6-(4-methylphenoxy)-1-(tetrahydro-2H-Piran-4-yl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,

N²-{[5-chloro-1-(2-ethoxyethyl)-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate, and

N²-{[5-chloro-6-(3,4-differenl)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate and

their pharmaceutically acceptable salts.

The compound (1) can be obtained, for example, in accordance with the method below.

The scheme of reactions 1

where R¹, R², R³, R⁴, R^5a, R^5b, R⁶, R⁷, L and X have the meanings defined above.

The compound (1) can be obtained by subjecting the compound (1-1) recovery aminating with the appropriate amine compounds. As a solvent, you can use ethereal solvent, t is such as tetrahydrofuran, 1,4-dioxane and the like, halogenated solvents such as dichloromethane, chloroform, 1,2-dichloroethane and the like, alcohol solvents such as methanol, ethanol and the like, ethyl acetate, N,N-dimethylformamide, acetonitrile and the like. Of them tetrahydrofuran, dichloromethane and methanol are preferred. As a reducing agent can be used borohydride sodium, triacetoxyborohydride sodium, cyanoborohydride sodium and the like. The reaction temperature ranges from -20°C to the boiling temperature used in the reaction solvent, and particularly preferably in the range of 0°C to about room temperature. Molecular sieves or sodium sulfate can be added as an agent of dehydration. You can add acetic acid or hydrochloric acid as an additive.

The compound (1A), which is a compound (1), where R⁴and R^5aunrelated, can also be obtained from compound (1-1) in accordance with the method represented in the reaction Scheme 2 below.

The scheme of reactions 2

where R¹, R², R³, R⁴, R^5a, R^5b, R⁶, R⁷, L and X have the meanings defined above, except that R⁴and R^5anot connected, and Y represents a removable group such as halogen atom, methyloxirane, tosyloxy the group and such.

The compound (1-1) is subjected to reductive aminating using the compounds (1-2) to obtain the compounds (1-3) and the compound (1-3) is subjected to interaction with the compound (1-4) in the presence of a base in a solvent such as an ether solvent (e.g. tetrahydrofuran, 1,4-dioxane and the like), halogenated solvent (e.g. dichloromethane, chloroform, 1,2-dichloroethane and the like), ethyl acetate, N,N-dimethylformamide, acetonitrile and the like, at temperatures from 0°C to the boiling temperature used in the reaction solvent to obtain the compound (1A). Although the base is not specifically limited, can be used inorganic bases such as potassium carbonate, cesium carbonate, sodium hydroxide, sodium hydride, potassium hydride, tert-piperonyl potassium and the like, and organic bases such as triethylamine, diisopropylethylamine and the like.

In addition, the compound (1) can also be obtained in accordance with the method represented in the reaction Scheme 3 below.

The reaction scheme 3

where R¹, R², R³, R⁴, R^5a, R^5b, R⁶, R⁷, L, Y and X have the meanings defined above.

The compound (1) can be obtained by reacting compounds (1-5) with the appropriate amine compound in the presence of a base in a solvent such as ether is the solvent (for example, tetrahydrofuran, 1,4-dioxane and the like), halogenated solvent (e.g. dichloromethane, chloroform, 1,2-dichloroethane and the like), ethyl acetate, N,N-dimethylformamide, acetonitrile and the like, at temperatures from 0°C to the boiling temperature used in the reaction solvent. Although the base is not specifically limited, can be used inorganic bases such as potassium carbonate, cesium carbonate, sodium hydroxide, sodium hydride, potassium hydride, tert-piperonyl potassium and the like, and organic bases such as triethylamine, diisopropylethylamine and the like.

The compound (1B), which is a compound (1), where R⁴represents a hydrogen atom, can be obtained, for example, shown in reaction Scheme 4 below.

The reaction scheme 4

where R¹, R², R³, R^5a, R^5b, R⁶, R⁷, L, Y and X have the meanings defined above.

The compound (1B) can be obtained by reacting compound (1-7), which is produced from compound (1-5) (1-6), in the same manner as in the reaction Scheme 3, in an acidic solvent such as triperoxonane acid, triftormetilfullerenov acid, hydrochloric acid, sulfuric acid and the like, at temperatures ranging from room temperature to the boiling point of COI is lisemore in the reaction solvent. More preferably, when the reaction is carried out in triperoxonane acid at a temperature of about 50°C.

The above compounds (1-1) and (1-5) can be obtained by the method presented below, and a similar method.

Of the above compounds (1-1), the compound (2-1) can be obtained, for example, shown in reaction Scheme 5 below.

The reaction scheme 5

where R²and R³have the meanings given above.

The compound (2-3) can be obtained by reacting 2,4-deformirovannoe with compound (2-2) in the presence of a base in a solvent such as an ether solvent (e.g. tetrahydrofuran, dimethoxyethane, 1,4-dioxane and the like), N,N-dimethylformamide, acetonitrile and the like, at temperatures ranging from room temperature to the boiling temperature used in the reaction solvent. As a basis you can use potassium carbonate, cesium carbonate, sodium hydroxide, sodium hydride, potassium hydride, tert-piperonyl potassium and the like, and preferably using potassium carbonate. As the preferred solvent is 1,4-dioxane.

The compound (2-5) can be obtained by reacting compound (2-3) with compound (2-4) in the presence of a base, in a solvent such as an ether solvent (e.g. tetrahydrofuran, DIMET xitan, 1,4-dioxane and the like), N,N-dimethylformamide, acetonitrile and the like, at temperatures ranging from room temperature to the boiling temperature used in the reaction solvent. As a basis you can use potassium carbonate, cesium carbonate, sodium hydroxide, sodium hydride, potassium hydride, tert-piperonyl potassium and the like, and preferably using cesium carbonate. As the preferred solvent is 1,4-dioxane.

The compound (2-6) can be obtained by restoring the nitro group of the compound (2-5) to the amino group. Recovery used in this reaction can be carried out in a conventional reducing conditions. Preferred are catalytic reduction using palladium on carbon and the like, recovery using metal, such as iron and the like, and the like, the Solvent used for the reduction is preferably chosen in accordance with the terms of recovery. For example, catalytic reduction is chosen methanol, ethanol, tetrahydrofuran, ethyl acetate, and the like, and to restore using a metal, such as iron and the like, choose tetrahydrofuran, acetic acid, methanol, ethanol, water and the like. Catalytic reduction is preferably carried out at room temperature, and recovering the use of metal, such as iron and the like, is preferably carried out at a temperature from 50°C to the boiling temperature used in the reaction solvent.

The compound (2-1) can be obtained by mixing compound (2-6) with glycolic acid and heating them at a temperature from 100°C to 150°C and by oxidation of the hydroxyl group obtained the corresponding cyclic compounds. Oxidation used for this reaction can be carried out in the normal oxidative conditions. Their examples include oxidation using manganese dioxide, chromium, etc. and oxidation of organic oxidizer represented by dimethyl sulfoxide. Oxidation using manganese dioxide and the oxidation method Swarna are preferred. Of these oxidation using manganese dioxide is particularly preferred. The solvent used for the oxidation, preferably chosen in accordance with the conditions of oxidation. For example, for oxidation using metal preferably chosen halogenated solvents such as dichloromethane, chloroform and the like, and ether solvents such as tetrahydrofuran, dimethoxyethane, 1,4-dioxane and the like. For oxidation of organic oxidant halogenated solvents such as dichloromethane, chloroform is similar, are preferred. Oxidation using metal preferably carried out at room temperature, and oxidation of the organic oxidant is preferably carried out at a temperature from -78°C to room temperature.

In the above compounds (1-1), the compound (3-1) can also be obtained, for example, shown in reaction Scheme 6 below.

The scheme of reactions 6

where R²and R³have the meanings given above.

The compound (3-4) can be obtained by reacting compound (3-2) with the compound (3-3) in the presence of a base in a solvent such as an ether solvent (e.g. tetrahydrofuran, dimethoxyethane, 1,4-dioxane and the like), N,N-dimethylformamide, acetonitrile and the like, at temperatures ranging from room temperature to the boiling temperature used in the reaction solvent. As a basis you can use potassium carbonate, cesium carbonate, sodium hydroxide, sodium hydride, potassium hydride, tert-piperonyl potassium and the like, and preferably using potassium carbonate. As the preferred solvent is 1,4-dioxane.

Connection (3-5) can be obtained by restoring the nitro group of the compound (3-4) to the amino group. Recovery used in this reaction, predpochtite the flax is a recovery using metal, such as iron, tin and the like, and the like, the Solvent used for recovery, preferably represents tetrahydrofuran, acetic acid, methanol, ethanol, water and the like. Recovery using metal preferably carried out at a temperature from 50°C to the boiling temperature used in the reaction solvent.

The compound (3-6) can be obtained by mixing compound (3-5) with glycolic acid and heating them at a temperature from 100°C to 150°C. the Compound (3-7) can be obtained by oxidation of the hydroxyl group of the compound (3-6). Oxidation used for this reaction can be carried out in the normal oxidative conditions. Their examples include oxidation using manganese dioxide, chromium and the like, and oxidation of organic oxidizer represented by dimethyl sulfoxide. Oxidation using manganese dioxide and the oxidation method Swarna are preferred. Of these oxidation using manganese dioxide is particularly preferred. The solvent used for the oxidation, preferably chosen in accordance with the conditions of oxidation. For example, for oxidation using metal preferred are halogenated solvent such as dichloromethane, chloroform and the like, ether R is storytell, such as tetrahydrofuran, dimethoxyethane, 1,4-dioxane and the like, and for oxidation of organic oxidant preferred are halogenated solvent such as dichloromethane, chloroform and the like. Oxidation using metal preferably carried out at room temperature, and oxidation of the organic oxidant is preferably carried out at a temperature from -78°C to room temperature.

The compound (3-1) can be obtained by reacting compounds (3-7) with the appropriate compound of boranova acid using a palladium catalyst, a ligand and a base in a solvent such as dimethoxyethane, 1,4-dioxane, toluene, ethanol and the like, at temperatures ranging from room temperature to the boiling temperature of the solvent. Examples of the palladium catalyst include, but are not limited to, palladium acetate, tetranitroaniline palladium, tribenzylamine dipalladium and the like. Although the ligand is not specifically limited, and its examples include triphenylphosphine, tri-o-tolylphosphino, three-tert-butylphosphine and the like. Although the base is not specifically limited, and its examples include sodium carbonate, potassium carbonate, cesium carbonate and the like.

In the above compounds (1-1), the compound (4-1) can be obtained, for example, in soo is according to the way represented in the reaction Scheme 7 below.

The scheme of reactions 7

where R²and R³have the meanings given above.

The compound (4-3) can be obtained by reacting compound (3-6) with compound (4-2) using a copper catalyst, a ligand and a base, in a solvent such as N-methylpyrrolidine, 1,4-dioxane, dimethylsulfoxide, N,N-dimethylformamide and the like, at temperatures ranging from room temperature to the boiling temperature of the solvent. Although copper catalyst is not specifically limited, and its examples include copper iodide, copper bromide, copper chloride and the like. Although the ligand is not specifically limited, and its examples include 2,2,6,6-tetramethylheptane-3,5-dione, N,N-dimethylglycine and the like. Although the base is not specifically limited, and its examples include sodium carbonate, potassium carbonate, cesium carbonate and the like.

The compound (4-1) can be obtained by oxidation of the hydroxyl group of the compound (4-3). Oxidation used for this reaction can be carried out in the normal oxidative conditions. Examples include oxidation using manganese dioxide, chromium and the like, and oxidation of organic oxidizer represented by dimethyl sulfoxide. Oxidation using manganese dioxide and the oxidation method Swarna site are titlename. Of these oxidation using manganese dioxide is particularly preferred. The solvent used for the oxidation, preferably chosen in accordance with the conditions of oxidation. For example, for oxidation using metal preferably chosen halogenated solvents such as dichloromethane, chloroform and the like, and ether solvents such as tetrahydrofuran, dimethoxyethane, 1,4-dioxane and the like. For oxidation of organic oxidant preferred are halogenated solvents such as dichloromethane, chloroform and the like. Oxidation using metal preferably carried out at room temperature, and oxidation of the organic oxidant is preferably carried out at a temperature from -78°C to room temperature.

In the above compounds (1-1), the compound (5-1) can be obtained, for example, shown in reaction Scheme 8 below.

The scheme of reactions 8

where R², R³and Y have the meanings given above.

The compound (5-4) can be obtained by reacting compound (5-2) with compound (5-3) in the presence of a base in a solvent such as an ether solvent (e.g. tetrahydrofuran, dimethoxyethane, 1,4-dioxane and the like), N,N-dim is telharmonic and the like, at a temperature ranging from room temperature to the boiling temperature used in the reaction solvent. As a basis you can use potassium carbonate, cesium carbonate, sodium hydroxide, sodium hydride, potassium hydride, tert-piperonyl potassium and the like, and preferably using potassium carbonate. As the preferred solvent is N,N-dimethylformamide.

The compound (5-1) can be obtained from compound (5-4) in the same manner as in the reaction Scheme 5.

In the above compounds (1-1), the compound (6-1) can be obtained, for example, according to reaction Scheme 9, below.

The reaction scheme 9

where R²and R³have the meanings given above.

The compound (6-3) can be obtained by reacting 2,6-dichloro-3-nitropyridine with compound (6-2) in the presence of a base in a solvent such as an ether solvent (e.g. tetrahydrofuran, dimethoxyethane, 1,4-dioxane and the like), N,N-dimethylformamide, acetonitrile and the like, at temperatures ranging from room temperature to the boiling temperature used in the reaction solvent. As a basis you can use potassium carbonate, cesium carbonate, sodium hydroxide, sodium hydride, potassium hydride, tert-piperonyl potassium and the like can be used, and prefer is Ino use potassium carbonate. As the preferred solvent is 1,4-dioxane.

Connection (6-5) can be obtained by reacting compound (6-3) with compound (6-4) in the presence of a base, in a solvent such as an ether solvent (e.g. tetrahydrofuran, dimethoxyethane, 1,4-dioxane and the like), N,N-dimethylformamide, acetonitrile and the like, at temperatures ranging from room temperature to the boiling temperature used in the reaction solvent. As a basis you can use potassium carbonate, cesium carbonate, sodium hydroxide, sodium hydride, potassium hydride, tert-piperonyl potassium and the like, and preferably using cesium carbonate. As the preferred solvent is 1,4-dioxane.

The compound (6-1) can be obtained from compound (6-5) in the same manner as in the reaction Scheme 5.

In the above compounds (1-1), the compound (7-1) can be obtained, for example, shown in reaction Scheme 10, below.

The reaction scheme 10

where R²and R³have the meanings given above.

The compound (7-2) can be obtained from compound (6-3) in the same manner as in reaction Scheme 6.

The compound (7-1) can be obtained by reacting compound (7-2) with the appropriate compound of boranova acid using paradiesvogelschi, ligand and a base in a solvent such as dimethoxyethane, 1,4-dioxane, toluene, ethanol and the like, at temperatures ranging from room temperature to the boiling temperature of the solvent. Examples of the palladium catalyst include, but are not limited to, palladium acetate, tetranitroaniline palladium, tribenzylamine dipalladium and the like. Although the ligand is not specifically limited, and its examples include triphenylphosphine, tri-o-tolylphosphino, three-tert-butylphosphine and the like. Although the base is not specifically limited, and its examples include sodium carbonate, potassium carbonate, cesium carbonate and the like.

The above compound (1-5) can be obtained from compound (8-1), for example, shown in reaction Scheme 11 below.

The reaction scheme 11

where R¹, R², R³, L, X and Y have the meanings given above.

As a stage of transformation in the group that you want where you want to remove the group Y represents methyloxirane or tailorshop corresponding chloride (methylchloride, taillored) is subjected to interaction in the presence of a base, such as triethylamine, pyridine and the like, to obtain the corresponding mesyl or toiley form. When the deleted group, Y represents a halogen atom, you can use the methods, opisanie Comprehensive Organic Transformation [R.C. Larock, VCH Publishers Inc. (1989)], 4th Edition Jikken Depending Kouza (Maruzen), Shinjikken Called Koza (Courses in Experimental Chemistry) (Maruzen) and the like, for Example, the corresponding bromide can be obtained by adding tribromide phosphorus in tetrahydrofuran.

Each of the above reactions can be carried out in accordance with methods described in the examples of the present description, Comprehensive Organic Transformation [R.C. Larock, VCH Publishers Inc. (1989)], 4th Edition Jikken Depending Kouza (Maruzen), Shinjikken Called Koza (Courses in Experimental Chemistry) (Maruzen).

In addition, the compounds used as starting substances in the above methods of preparation, can appropriately be obtained by using commercially available product or in accordance with the method, known to specialists in this field.

In addition, when receiving the connection according to the present invention or its pharmaceutically acceptable salt, you can protect or unprotect a functional group such as hydroxyl group, carboxyl group, amino group and the like, at any stage, where it is needed. The type of the protective group and the method of introduction and removal of the protective group may be a method known to specialists in this field. For example, you can refer to “Protective Groups in Organic Synthesis (T.W. Greene et al., John Wiley & Sons, Inc. published in 1991), and the like.

When the compound (1) contains a group capable of salt formation, in his article is ucture, you can convert, if necessary, an acid additive salt with inorganic acid or organic acid or basic additive salt, which is acceptable as medicines. Examples of pharmaceutically acceptable acid additive salts include salts of inorganic acids such as hydrochloride, hydrobromide, sulfate, phosphate and the like, salts with organic carboxylic acid, such as formate, acetate, fumarate, maleate, oxalate, citrate, malate, tartrate, aspartate, glutamate and the like, salts with sulfonic acid such as methanesulfonate, bansilalpet, p-toluensulfonate, hydroxybenzenesulfonate, dihydroxybenzenesulfonic and the like, and examples of pharmaceutically acceptable basic additive salts include ammonium salt, lithium salt, sodium salt, potassium salt, calcium salt, magnesium salt and the like.

In addition, the present invention also encompasses hydrate and MES, such as ethanolate and the like, compound (1) or its pharmaceutically acceptable salt. In addition, the present invention encompasses any tautomer and a stereoisomer, such as optical isomer and the like, and any crystalline form of compound (1). They can appropriately be cleaned using a method well-known to specialists in this field, is such as column chromatography on silica gel, WAHI, ion exchange chromatography, recrystallization and the like.

To obtain the above optical isomer in pure form, you can use the optical separation, known to specialists in this field. In particular, when the compound of the present invention or an intermediate alkaline compound contains a functional group, it can form a salt with an optically active acid (e.g., monocarboxylic acids such as mandelic acid, N-benzyloxyethanol, lactic acid and the like, dicarboxylic acids such as tartaric acid, o-diisopropylidene acid, malic acid and the like, sulfonic acids such as camphorsulfonic acid, broncontrolebeheer acid and the like) in an inert solvent. In addition, when the compound of the present invention or an intermediate compound contains an acidic functional group, it can also form a salt with an optically active amine (e.g., organic amines such as α-phenethylamine, kinin, quinidine, cinchonidine, cinchonine, strychnine, and the like). The temperature for the formation of salts is in the range from room temperature to the boiling temperature of the solvent.

A new compound containing the bicyclic heterocycle, according to the present invention, or E. what about the pharmaceutically acceptable salts have activity of inhibiting SNSy, and they can be used as a therapeutic or preventive medicines for neuropathic pain and nociceptive pain. Examples of neuropathic pain include neuralgia after surgery in the lumbar region, diabetic neuropathy, neuralgia after shingles, reflex simpaticheskuyu dystrophy, phantom limb pains, spinal cord injury, cancerous pain, at a later stage and prolonged postoperative pain. Examples of nociceptive pain include back pain, abdominal pain, rheumatoid arthritis, pain in osteoarthritis and the like. In addition, the compound of the present invention or its pharmaceutically acceptable salt can also be used as a therapeutic or preventive medicines from urination disorders. Examples of urination disorders here include frequent urination, cystalgia in benign prostate hyperplasia and the like. In addition, it can also be used as a therapeutic or prophylactic medication to suppress abnormal nerve inflammation in the cerebellum in multiple sclerosis. As a drug without side effects, originating from tissues that are not related to the nervous system or the Central n is rvnoy system, connection with SNS-selective inhibitory activity, is preferable.

Therapeutic or prophylactic drug of the present invention from neuropathic pain, nociceptive pain, urination disorders or multiple sclerosis can contain various optional components to obtain the drug, such as conventionally used carrier, binder, stabilizer, excipient, diluent, pH-regulating buffer agent, baking powder, solubilizers substance, a substance that promotes dissolution, isotonic agent and the like, which are pharmaceutically acceptable. In addition, these therapeutic or prophylactic drugs can be administered orally or parenterally. For example, for oral administration, the drug can be administered orally in the form that is usually used, for example, in dosage forms such as tablet, pill, powder, granule, capsule, syrup, emulsion, suspension and the like. For parenteral administration, the drug may be formulated in the form of the drug in the form of, for example, intravenous injection (drip infusion), intramuscular injection, subcutaneous injection, liniment, eye drops, eye ointments, etc.

Solid preparation such to the to the tablet, prepared by mixing the active ingredient with a conventional pharmaceutically acceptable carrier or excipient, such as lactose, sucrose, corn starch and the like, binders such as crystalline cellulose, hydroxypropylcellulose, polyvinylpyrrolidone, hypromellose and such, baking powder, such as sodium carboxymethyl cellulose, sodium starch glycolate and the like, a lubricant such as stearic acid, magnesium stearate and the like, preservative, etc.

For parenteral administration the active ingredient can be dissolved or suspended in a physiologically acceptable medium such as water, physiological saline solution, oil, aqueous glucose solution and the like, and you can add an emulsifier, stabilizer, salt for regulating the osmotic pressure or buffer agent as auxiliary additives, if necessary.

The preparation of the compounds of the present invention can be obtained in accordance with the traditionally used method. For example, the tablet can be obtained by mixing compound of Example 1 (20 mg), lactose (100 mg), crystalline cellulose (25 mg) and magnesium stearate (1 mg) and tabletting the mixture.

Although the dose and frequency of injection varies depending on the method of administration and the age,body weight, the disease severity of patients and so on, the way local injection at the site of lesions caused by disease, trauma, is preferred. Also preferably, the administration of a medicinal product once or twice or more a day. With the introduction of two or more times, preferably sequential introduction or re-introduction with appropriate intervals.

Dose is 10 mg to 2 g, preferably 1 mg to 1 g, more preferably 10-100 mg amount of the active ingredient per adult patient per one introduction that can be entered as a single injection or multiple injections throughout the day. For parenteral administration, the dose may be about 0.1-100 mg/day, more preferably from 0.3 to 50 mg/day for an adult patient, and can be entered as a single injection or multiple injections throughout the day. To reduce the frequency of injection can also use the drug slow release.

In addition, therapeutic or prophylactic drug of the present invention from neuropathic pain, nociceptive pain, urination disorders or multiple sclerosis can also be used as a medicine for animals.

EXAMPLES

The present invention is explained in more detail hereinafter with Silkina Reference examples and Examples; however, the technical scope of the present invention is not limited to such examples, and other Compounds were identified by using the absorption spectrum of hydrogen nuclear magnetic resonance (¹H-NMR), etc.

Further, in some cases, there may be used the abbreviations listed below, to simplify description of the present invention.

Me: methyl, Et: ethyl, Pr: propyl, iPr: isopropyl, Ph: phenyl, Ac: acetyl, Boc: tert-butoxycarbonyl, Bn: benzyl, TBDMS: tert-butyldimethylsilyl, PyBOP: hexaphosphate benzotriazol-1-yl-oxy-Tris(pyrrolidino)of phosphonium, J: the interaction constant, s: singlet, d: doublet, DD: double doublet, DDD: 4 doublet, dt: 3 doublet, t: triplet, dt: double triplet, square: Quartet, Quint.: quintet, usher.: broadened, m: multiplet.

Unless otherwise specified, used as starting compounds, the compounds used in the reactions of the reagents and solvents are commercially available products.

Reference example 1:

To a solution of 2,4-deformirovannoe (15 g, 94 mmol) in dioxane (300 ml) was added potassium carbonate (14.4 g, 104 mmol) and 2-amoxicillin (8,4 g, 104 mmol) and the mixture was stirred at room temperature overnight. To the reaction mixture were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated salt concrete is, was dried over sodium sulfate and concentrated under reduced pressure to obtain the target product (21 g, 98%).

¹H-NMR (CDCl₃) δ 1,25 (t, J=7,1 Hz, 3H), 3.43 points (sq, J=5,2 Hz, 2H), to 3.58 (sq, J=7,1 Hz, 2H), and 3.72 (t, J=5,2 Hz, 2H), 6,37 (DDD, J=9,5, 7,3, 2.5 Hz, 1H), 6,51 (DD, J=a 11.5 and 2.5 Hz, 1H), they were 8.22 (DD, J=a 9.5 and 6.1 Hz, 1H), scored 8.38 (user., 1H).

Reference example 2:

To a solution (60 ml) of the compound (3.0 g, 13,2 mmol)obtained in Reference example 1 in dioxane) was added cesium carbonate (6.4 g, of 19.7 mmol) and phenol (1.5 g, 15.8 mmol) and the mixture was heated to 80°C. After stirring for 7 hours to the reaction mixture were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure to obtain the target product (4.1 g, 100%).

¹H-NMR (CDCl₃) δ of 1.23 (t, J=7.0 Hz, 3H), 3,34 (sq, J=5,2 Hz, 2H), 3,55 (sq, J=7,0 Hz, 2H), to 3.67 (t, J=5,2 Hz, 2H), from 6.22 (DD, J=9,4, 2.5 Hz, 1H), 6,29 (d, J=2.5 Hz, 1H), 7,07 for 7.12 (m, 2H), 7.23 percent (m, 1H), 7,35-7,45 (m, 2H)that is 8.16 (d, J=9.4 Hz, 1H), 8,39 (user., 1H).

Reference example 3-1:

To a solution (50 ml) of the compound (1.8 g, 6.0 mmol)obtained in Reference example 2 in ethanol was added 10% palladium on carbon (1 g) and the mixture was stirred at room temperature for 4 hours in hydrogen atmosphere. The reaction mixture was filtered through celite and the filtrate to what has centriole and dried under reduced pressure to obtain the desired product (1.4 g, 86%).

¹H-NMR (CDCl₃) δ 1,22 (t, J=7.0 Hz, 3H), 3,21 (t, J=5,2 Hz, 2H), 3,23 (user., 2H), 3,53 (sq, J=7,0 Hz, 2H), to 3.67 (t, J=5,2 Hz, 2H), 6,34 (DD, J=8,3, 2.6 Hz, 1H), 6,40 (d, J=2.6 Hz, 1H), to 6.67 (d, J=8,3 Hz, 1H), 6,92? 7.04 baby mortality (m, 3H), 7.24 to 7,30 (m, 2H).

Reference example 3-2:

Above the target product can be obtained as follows.

To a suspension of (3:2:1, 120 ml) of iron (13,9 g, 0.25 mol) and ammonium chloride (6.6 g, 0.12 mol) in a mixture of tetrahydrofuran-methanol-water was added dropwise a solution (60 ml) of the compound (9.8 g, 32 mmol)obtained in Reference example 2 in a mixed solvent (3:2:1) tetrahydrofuran-methanol-water when heated to the boiling temperature under reflux. After stirring for 2 hours the reaction mixture was allowed to cool and filtered through celite. To the filtrate was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure to obtain the target product (8.7 g, 100%).

Reference example 4:

To the compound (5.0 g, 18.4 mmol)obtained in Reference example 3 was added glycolic acid (8 g) and the mixture was stirred at 120°C for 30 minutes. After cooling, to the reaction mixture were added water and chloroform and the mixture is neutralized using 30% aqueous sodium hydroxide solution with cooling the AI ice. The organic layer was extracted, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (chloroform:methanol=50:1-30:1) to obtain the desired crude product (4.1 g).

Reference example 5:

To a solution of compound (4.1 g)obtained in Reference example 4 in dichloromethane (100 ml) was added manganese dioxide (8 g) and the mixture was stirred at room temperature. After stirring for 2 hours the reaction mixture was filtered through celite and the filtrate was concentrated. The residue was purified on a column of silica gel (ethyl acetate:hexane=1:2) to obtain the target product (3.5 g, 61%, stage 2).

¹H-NMR (CDCl₃) δ of 1.03 (t, J=7.0 Hz, 3H), 3,37 (sq, J=7,0 Hz, 2H), of 3.73 (t, J=5.3 Hz, 2H), of 4.66 (t, J=5.3 Hz, 2H),? 7.04 baby mortality-7,20 (m, 5H), 7,34-7,41 (m, 2H), 7,86 (d, J=8,8 Hz, 1H), of 10.05 (s, 1H).

Reference example 6:

Target the crude product obtained from 2,4-deformirovannoe (20,0 g, 126 mmol) and 4-terfenol in the same manner as in Reference example 1-4, recrystallized from chloroform/hexane and then recrystallized from acetonitrile to obtain the desired product (23.3 g, 56%, 4 steps).

¹H-NMR (CDCl₃) δ of 1.05 (t, J=7.0 Hz, 3H), 3,37 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5,1 Hz, 2H), 4,34 (t, J=5,1 Hz, 2H), 4,89 (s, 2H), 6.89 in-7,03 (m, 6H), 7,58 (m, 1H).

Reference example 7:

The target product was obtained in the same manner as in Reference example 5, from compound obtained in Reference example 6.

¹H-NMR (CDCl₃) δ 0,99 (t, J=7.0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 2H), 3,69 (t, J=5,1 Hz, 2H), to 4.62 (t, J=5,1 Hz, 2H), 6,92-to 7.09 (m, 6H), 7,81 (m, 1H), 10,00 (s, 1H).

Example 1: N²-{[1-(2-ethoxyethyl)-6-phenoxy-1H-benzimidazole-2-yl]methyl}-L-alaninate

To a solution of the compound (2.0 g, 6.5 mmol)obtained in Reference example 5, in dichloromethane (50 ml) were added hydrochloride (L)-alaninemia (0.96 g, 7.7 mmol) and the mixture was stirred at room temperature. After stirring for 1 hour to the mixture was added triacetoxyborohydride sodium (1.6 g, 7.7 mmol) and the mixture was stirred for 2 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with ethyl acetate. The organic layer was extracted, washed with water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (chloroform:methanol=50:1-10:1) to obtain the target product (0,59 g, 24%).

¹H-NMR (CDCl₃) δ a 1.08 (t, J=7,1 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 3,38 (sq, J=7,1 Hz, 2H), 3,68 (t, J=5,1 Hz, 2H), Android 4.04 (d, J=14,7 Hz, 1H), 4,12 (d, J=14,7 Hz, 1H), 4,17-4,32 (m, 2H), 5,50 (users, 1H), 6,98-7,02 (m, 4H), to 7.09 (m, 1H), 7,28 and 7.36 (m, 3H), 7,68 (m, 1H).

The above connection takemore be obtained as follows.

To a solution of the compound (0.15 g, 0.48 mmol)obtained in Reference example 5 in tetrahydrofuran (10 ml) were added hydrochloride (L)-alaninemia (0.18 g, 1,45 mmol), sodium sulfate (3 g) and triethylamine (0,20 ml) and the mixture was stirred at room temperature. After stirring for 30 minutes, to the mixture was added cyanoborohydride sodium (45 mg, to 0.72 mmol) and the mixture was stirred for 2 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with chloroform. The organic layer was extracted, washed with saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (chloroform:methanol=50:1-10:1) to obtain the target product (0.09 g, 49%).

Example 2: N²-{[1-(2-ethoxyethyl)-6-phenoxy-1H-benzimidazole-2-yl]methyl}glycinamide

To a solution of compound (44 mg, 0.14 mmol)obtained in Reference example 5, in methanol (3 ml) were added hydrochloride glycinamide (31 mg, 0.28 mmol) and the mixture was stirred at room temperature. After stirring for 1 hour to the mixture was added cyanoborohydride sodium (18 mg, 0.28 mmol) and the mixture was stirred over night. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with ethyl acetate. The organic is the second layer was extracted, washed with water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (chloroform:methanol=50:1-10:1) to obtain the target product (23 mg, 43%).

¹H-NMR (CDCl₃) δ a 1.08 (t, J=7.0 Hz, 3H), 3,38 (sq, J=7,0 Hz, 2H), 3,42 (s, 2H), 3,68 (t, J=5,1 Hz, 2H), 4,10 (s, 2H), 4.26 deaths (t, J=5,1 Hz, 2H), 5,72 (users, 1H), of 6.96-7,02 (m, 4H), was 7.08 (m, 1H), 7,21 (users, 1H), 7,28 and 7.36 (m, 2H), 7,68 (m, 1H).

Example 3: N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}glycinamide

The target product was obtained in the same manner as in Example 2 from the compound obtained in Reference example 7.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), 3,39 (sq, J=7,0 Hz, 2H), 3,42 (s, 2H), 3,69 (t, J=5.0 Hz, 2H), 4,10 (s, 2H), 4.26 deaths (t, J=5.0 Hz, 2H), 5,54 (users, 1H), 6,93-7,05 (m, 6H), 7,18 (users, 1H), to 7.67 (m, 1H).

Example 4: N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-valinamide

The target product was obtained in the same manner as in Example 1 from the compound obtained in Reference example 7, and the hydrochloride of (L)-valinamide.

¹H-NMR (CDCl₃) δ 0,99 (d, J=7,0 Hz, 3H), of 1.02 (d, J=7,0 Hz, 3H), of 1.08 (t, J=7.0 Hz, 3H), of 2.08 (m, 1H), 2,97 (d, J=5.5 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5,1 Hz, 2H), 3,98 (d, J=14,5 Hz, 1H), 4,15 (d, J=14,5 Hz, 1H), 4,17-and 4.40 (m, 2H), 5.56mm (users, 1H), 6,93-7,01 (m, 7H), to 7.67 (m, 1H).

Example 5: N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-shall benzimidazol-2-yl]methyl}-2-methylalanine

The target product was obtained in the same manner as in Example 1 from the compound obtained in Reference example 7 and 2-methylalanine, which is a known connection.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.46 (s, 6H), 3,38 (sq, J=7,0 Hz, 2H), 3,69 (t, J=5,1 Hz, 2H), was 4.02 (s, 2H), 4,24 (t, J=5,1 Hz, 2H), 5,43 (users, 1H), 6,93-7,05 (m, 6H), of 7.48 (users, 1H), 7,68 (m, 1H).

Examples 6-58:

Connection Examples 6-58 presented in Tables 1-9 were obtained in the same manner as in Reference examples 1 to 7, Example 1 or Example 2, from 2,4-deformirovannoe and using commercially available or known compounds.

Table 1-1
Example	The structural formula	1H-NMR (CDCl3) δ
6		of 1.40 (d, J=7,0 Hz, 3H), 1,79-of 1.88 (m, 2H), 2,42-of 2.58 (m, 2H), 3,28 (sq, J=7,0 Hz, 1H), 3,51-to 3.58 (m, 2H), a 4.03 (d, J=14,8 Hz, 1H), 4,11 (d, J=14,8 Hz, 1H), 4,13-4,19 (m, 2H), 4,48 (m, 1H), 5,45 (users, 1H), 6,91-7,05 (m, 6H), 7,26 (users, 1H), to 7.67 (d, J=8,8 Hz, 1H).
7		0,98-1,05 (m, 2H), 1,15-of 1.27 (m, 2H), 1,44 (d, J=7,0 Hz, 3H), 3,18 (m, 1H), 3,35 (sq, J=7,0 Hz, H), 4.09 to (d, J=15.6 Hz, 1H), 4,17 (d, J=15.6 Hz, 1H), 5,35 (users, 1H), 6,91-7,05 (m, 5H), 7,14 (d, J=2.4 Hz, 1H), 7,25 (users, 1H), 7,63 (d, J=8,8 Hz, 1H).
8		of 1.47 (s, 6H), 1,80 is 1.86 (m, 2H), 2,44-of 2.58 (m, 2H), 3,50-3,59 (m, 2H), 4,01 (s, 2H), 4,14-4,19 (m, 2H), 4,43 (m, 1H), of 5.84 (users, 1H), 6.90 to? 7.04 baby mortality (m, 5H), 7,16 (users, 1H), 7,26 (d, J=2.0 Hz, 1H), 7,66 (d, J=8,8 Hz, 1H).
9		of 1.40 (d, J=7,0 Hz, 3H), 1,58 (d, J=7,0 Hz, 6H), 3,30 (sq, J=7,0 Hz, 1H), 4,01 (d, J=14,7 Hz, 1H), 4,08 (d, J=14,7 Hz, 1H), 4,69 (m, 1H), 6,10 (users, 1H), 6,92-7,02 (m, 3H), 7,07 (m, 1H), 7,15 (users, 1H), 7,21 (m, 1H), 7,27-7,37 (m, 2H), 7,65 (d, J=8.6 Hz, 1H).

Table 1-2
10		was 1.58 (d, J=7,0 Hz, 6H), 3.43 points (s, 2H), 4,07 (s, 2H), 4,69 (m, 1H), 6,15 (users, 1H), 6,91-7,01 (m, 4H),? 7.04 baby mortality (m, 1H), 7,11 (users, 1H), 7,20 (d, J=1.9 Hz, 1H), 7.29 trend was 7.36 (m, 2H), to 7.64 (d, J=8,8 Hz, 1H).
11		of 1.42 (d, J=7,0 Hz, 3H), 1,82-2,04 (m, 2H), 2,44-of 2.58 (m, 2H), was 2.76-2.91 in (m, 2H), 3,30 (sq, J=7,0 Hz, 1H), 3,99 (d, J=14.1 Hz, 1H), 4,06 (d, J=14.1 Hz, 1H), 4,87 (m, 1H), 5,52 (users, 1H), 6,94-7,11 (m, 4H), 7,13 (users, 1H), 7,30-7,37 (m, 3H), 7,66 (d, J=8,8 Hz, 1H).

Table 2-1
Example	The structural formula	1H-NMR (CDCl3) δ
12		1,88-2,04 (m, 2H), 2,46 at 2.59 (m, 2H), was 2.76 of 2.92 (m, 2H), 3,44 (s, 2H), of 4.05 (s, 2H), 4,88 (m, 1H), 5,50 (users, 1H), 6,95 for 7.12 (m, 5H), 7,30 and 7.36 (m, 3H), 7,66 (d, J=8,8 Hz, 1H).
13		1,30-and 1.54 (m, 4H), USD 1.43 (d, J=6.8 Hz, 3H), of 2.06 (m, 1H), 3,22-3,37 (m, 3H), 3,86-4,10 (m, 6H), 5,51 (users, 1H), of 6.96-7,13 (m, 6H), 7,29-7,35 (m, 2H), to 7.67 (m, 1H).
14		1,32-and 1.54 (m, 4H), to 2.06 (m, 1H), 3,30 (td, J=11,5, 2,6 Hz, 2H), 3.45 points (s, 2H), 3,92-4,00 (m, 4H), 4,06 (s, 2H), 5,57 (users, 1H), of 6.96 for 7.12 (m, 6H), 7,30-7,37 (m, 2H), to 7.67 (m, 1H).
15		a 1.08 (t, J=7.0 Hz, 3H), 1,78-2,05 (m, 3H), to 2.29 (m, 1H), 2,60 (m, 1H), and 3.16 (m, 1H), 3,28-of 3.42 (m, 3H), 3,70 (t, J=5,2 Hz, 2H), 3,94 (d, J=14,3 Hz, 1H), 4,21 (d, J=14,3 Hz, 1H), 4,27-to 4.38 (m, 2H), 5,39 (users, 1H), 6,93-7,06 (m, 6H), to 7.64 (users, 1H), 7,68 (d, J=9.4 Hz, 1H).
16		1,32-of 1.52 (m, 4H), 1,80 to 2.35 (m, 5H), 2,59 (sq, J=8,4 Hz, 1H), 3,20-to 3.36 (m, 4H), 3,88-4,18 (who, 6H), 5,50 (users, 1H), of 6.96 for 7.12 (m, 5H), 7,28-7,38 (m, 2H), 7,44 (users, 1H), 7,68 (m, 1H).

Table 2-2
17		of 1.42 (d, J=6.8 Hz, 3H), 1,86-2,04 (m, 2H), 2,47-to 2.57 (m, 2H), 2,78-is 2.88 (m, 2H), 3,30 (sq, J=6,8 Hz, 1H), 3,99 (d, J=to 15.0 Hz, 1H), 4,06 (d, J=to 15.0 Hz, 1H), 4,87 (m, 1H), 5,45 (users, 1H), 6.90 to-7,06 (m, 5H), 7,12 (users, 1H), 7,27 (d, J=2.2 Hz, 1H), 7,66 (d, J=8,8 Hz, 1H).

Table 3-1
Example	The structural formula	1H-NMR (CDCl3) δ
18		1,86-to 2.06 (m, 2H), 2,30-of 2.58 (m, 2H), 2,75-2,90 (m, 2H), 3.43 points (s, 2H), of 4.05 (s, 2H), 4,87 (m, 1H), 5,59 (users, 1H), 6.90 to-7,10 (m, 6H), 7,27 (m, 1H), 7,65 (d, J=8,8 Hz, 1H).
19		of 1.56 (m, 1H), 1,80-to 2.06 (m, 6H), to 2.29 (m, 1H), 2,58 (sq, J=8.5 Hz, 1H), 3,18 (m, 1H), 3,32 (DD, J=9,8, a 5.4 Hz, 1H), 3,67-3,82 (m, 2H), 3,95 (d, J=14.4 Hz, 1H), 4,11-4,34 (m, 4H), 5,28 (users, 1H), of 6.96-7,10 (m, 5H), 7,29-7,35 (m, 2H), to 7.67 (users, 1H), 7,68 (d, J=8.5 Hz, 1H).
20		of 1.41 (d, J=7,1 Hz, 3H), of 1.55 (m, 1H), 1,80-of 1.93 (m, 2H), 2,10 (m, 1H), 3,35 (sq, J=7,1 Hz, 1H), 3,67-a 3.83 (m, 2H), 4,00-4,30 (m, 5H), 5,41 (users, 1H), 6,85-7,10 (m, 5H), 7,25-7,35 (m, 3H), to 7.67 (d, J=8.5 Hz, 1H).
21		of 1.55 (m, 1H), 1,80-of 2.08 (m, 6H), 2,28 (m, 1H), 2,61 (sq, J=8.6 Hz, 1H), up 3.22 (m, 1H), 3,33 (DD, J=9,7, a 5.4 Hz, 1H), 3,67-3,81 (m, 2H), 3,98 (d, J=14.6 Hz, 1H), 4,15-4,24 (m, 4H), 5,33 (users, 1H), of 6.96-7,10 (m, 5H), 7,29-7,35 (m, 2H), 7,55 (users, 1H), 7,68 (d, J=8.5 Hz, 1H).

Table 3-2
22		of 1.41 (d, J=6.8 Hz, 3H), and 1.56 (m, 1H), 1.85 to 1,95 (m, 2H), 2.05 is (m, 1H), 3,32 (sq, J=6,8 Hz, 1H), 3,67-a-3.84 (m, 2H), 4,03-4,22 (m, 5H), are 5.36 (users, 1H), 6,80-7,10 (m, 5H), 7.24 to 7,34 (m, 3H), to 7.67 (d, J=8.5 Hz, 1H).
23		2,02 (m, 2H), 3.27 to to 3.34 (m, 5H), of 3.45 (s, 2H), 4,07 (s, 2H), 4,21 (t, J=6,8 Hz, 2H), 5,78 (users, 1H), 6,98-7,10 (m, 5H), 7,21 (users, 1H), 7,30-7,35 (m, 2H), to 7.67 (m, 1H).

Table 4-1
Example	The structural formula	1H-NMR (CDCl3) δ
24		of 1.42 (d, J=6.8 Hz, 3H), 2.00 in of 2.26 (m, 2H), or 3.28 (s, 3H), 3,28-to 3.36 (m, 3H), 4,01 (d, J=14,5 Hz, 1H), 4,07 (d, J=14,5 Hz, 1H), 4,28 (t, J=6,8 Hz, 2H), 5,47 (users, 1H), 6,97-7,10 (m, 5H), 7.23 percent (users, 1H), 7,29-7,34 (m, 2H), to 7.67 (m, 1H).
25		1,74-of 2.38 (m, 8H), 3,44 (s, 2H), 4.09 to (s, 2H), 4,78 (m, 1H), 5,93 (users, 1H), 6,93-to 7.68 (m, 9H).
26		1,40-of 1.42 (m, 3H), 1,74-of 2.21 (m, 8H), 3,30 (sq, J=6,8 Hz, 1H), 4,00-4,11 (m, 2H), 4,72-of 4.77 (m, 1H), 5,76 (users, 1H), 6,94-to 7.68 (m, 9H).
27		of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,34 (sq, J=7,0 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5,1 Hz, 2H), Android 4.04 (d, J=14,8 Hz, 1H), 4,12 (d, J=14,8 Hz, 1H), 4,19-4.26 deaths (m, 2H), 5.40 to (users, 1H), 6,90-7,00 (m, 4H), 7.23 percent (users, 1H), 7.24 to 7,30 (m, 2H), 7,69 (m, 1H).
28		of 1.09 (t, J=7.0 Hz, 3H), 3,39 (sq, J=7,0 Hz, 1H), 3,42 (s, 2H), 3,69 (t, J=5.0 Hz, 2H), 4,10 (s, 2H), 4,27 (t, J=5.0 Hz, 2H), 6.90 to-7,00 (m, 4H), 7,18 (users, 1H), 7.24 to 7,30 (m, 3H), 7,68 (m, 1H).

Table 4-2
29		a 1.08 (t, J=7,0 is C, 3H), of 1.41 (d, J=6.8 Hz, 3H), 3,30-of 3.42 (m, 3H), 3,68-3,70 (m, 2H), Android 4.04 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,21-4,32 (m, 2H), 5,73 (users, 1H), 6,86-7,05 (m, 5H), 7,20-7,27 (m, 2H), 7,71 (m, 1H).

Table 5-1
Example	The structural formula	1H-NMR (CDCl3) δ
30		of 1.09 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), 3,39 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5.0 Hz, 2H), Android 4.04 (s, 2H), 4,27 (t, J=5.0 Hz, 2H), 5,49 (users, 1H), 6,85-7,06 (m, 5H), of 7.23 (t, J=8,1 Hz, 1H), of 7.48 (users, 1H), 7,71 (d, J=8,4 Hz, 1H).
31		of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5.0 Hz, 2H), a 4.03 (d, J=14,8 Hz, 1H), 4,12 (d, J=14,8 Hz, 1H), 4,22 (dt, J=15,1, 5.0 Hz, 1H), 4,28 (dt, J=15,1, 5.0 Hz, 1H), 5,63 (users, 1H), 6.89 in-7,19 (m, 5H), 7,26 (users, 1H), 7,47 (DD, J=7,9, and 1.6 Hz, 1H), 7,68 (DD, J=8,4, 0.7 Hz, 1H).
32		of 1.09 (t, J=7.0 Hz, 3H), of 1.46 (s, 6H), 3,38 (sq, J=7,0 Hz, 2H), 3,69 (t, J=5,1 Hz, 2H), a 4.03 (s, 2H), 4,25 (t, J=5,1 Hz, 2H), 5,55 (users, 1H), 6.89 in-to 7.18 (m, 5H), 7,45-of 7.48 (m, 2H), 7,68 (d, J=8,4 Hz, 1H).
33		of 1.47 (s, 6H), 1,86-2,04 (m, 2H), 2,45-to 2.57 (m, 2H), 2.77-to of 2.92 (m, 2H), 3.96 points (s, 2H), around 4.85 (m, 1H), 5,46 (users, 1H), 6,94-7,11 (m, 4H), 7,29-7,37 (m, 4H), to 7.67 (d, J=8,8 Hz, 1H).

Table 5-2
34		of 1.42 (d, J=7,0 Hz, 3H), 1,82-2,04 (m, 2H), 2,44-of 2.58 (m, 2H), was 2.76-2.91 in (m, 2H), 3,30 (sq, J=7,0 Hz, 1H), 3,99 (d, J=14.1 Hz, 1H), 4,06 (d, J=14.1 Hz, 1H), 4,87 (m, 1H), 5,52 (users, 1H), 6,94-7,11 (m, 4H), 7,13 (users, 1H), 7,30-7,37 (m, 3H), 7,66 (d, J=8,8 Hz, 1H).
35		of 1.46 (s, 6H), 1.57 in (m, 1H), 1,82 is 2.10 (m, 3H), 3,67-a-3.84 (m, 2H), 3.96 points-of 4.25 (m, 5H), are 5.36 (users, 1H), of 6.96-7,11 (m, 5H), 7,28-7,35 (m, 2H), of 7.48 (users, 1H), 7,68 (d, J=8.6 Hz, 1H).

Table 6-1
Example	The structural formula	1H-NMR (CDCl3) δ
36		a 1.08 (t, J=7.0 Hz, 3H), of 1.40 (d, J=7,0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5.0 Hz, 2H), a 4.03 (d, J=14,7 Hz, 1H), 4,12 (d, J=14,7 Hz, 1H), 4,17-4,32 (m, 2H), 5,95 (users, 1H), 6,98-7,10 (m, 5H), 7,29-7,35 (m, 3H), 7,68 (m, 1H).
37		a 1.01 (t, J=7,3 Hz, 3H), of 1.08 (t, J=7.0 Hz, 3H), 1.70 to of 1.84 (m, 2H), 3.15 in (t, J=6.3 Hz, 1H), 3,37 (sq, J=7,3 Hz, 2H), 3,68 (t, J=5,2 Hz, 2H), 4,01 (d, J=14.6 Hz, 1H), 4,13 (d, J=14.6 Hz, 1H), 4,21 (dt, J=15.2 in, and 5.2 Hz, 1H), 4,30 (dt, J=15,2, and 5.2 Hz, 1H), 5.56mm (users, 1H), 6,98-7,11 (m, 5H), 7,18 (users, 1H), 7,27-7,35 (m, 2H), 7,68 (m, 1H).
38		0,99 (d, J=6.9 Hz, 3H), of 1.02 (d, J=6.9 Hz, 3H), of 1.08 (t, J=7.0 Hz, 3H), of 2.08 (m, 1H), 2,97 (d, J=5.3 Hz, 1H), 3,37 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5,2 Hz, 2H), 3,99 (d, J=14.4 Hz, 1H), 4,14 (d, J=14,4 Hz, 1H), 4,22 (dt, J=15,2, and 5.2 Hz, 1H), 4,35 (dt, J=15,2, and 5.2 Hz, 1H), 5,80 (users, 1H), 6,97-7,11 (m, 6H), 7,27-7,35 (m, 2H), 7,68 (m, 1H).

39

of 1.09 (t, J=7.0 Hz, 3H), of 1.46 (s, 6H), 3,39 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5.0 Hz, 2H), a 4.03 (s, 2H), 4,24 (t, J=5.0 Hz, 2H), 5,76 (users, 1H), 6,97-7,10 (m, 5H), 7,27-7,35 (m, 2H), 7,51 (users, 1H), 7,69 (m, 1H).

Table 6-2
40		a 1.08 (t, J=7.0 Hz, 3H), 2,43 (s, 3H), 3,20 (s, 2H), 3,38 (sq, J=7,0 Hz, 2H), 3,71 (t, J=5,2 Hz, 2H), 3.96 points (s, 2H), 4,37 (t, J=5,2 Hz, 2H), of 5.84 (users, 1H), 6,98-7,11 (m, 5H), 7,27-7,35 (m, 2H), 7,38 (users, 1H), of 7.69 (m, 1H).
41		a 1.01 (t, J=7.4 Hz, 3H), of 1.08 (t, J=7.0 Hz, 3H), 1,69 is 1.86 (m, 2H), 3.15 in (t, J=6.3 Hz, 1H), 3,37 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5.0 Hz, 2H), 4.00 points (d, J=14.6 Hz, 1H), 4,12 (d, J=14.6 Hz, 1H), 4,19-to 4.33 (m, 2H,), 5,79 (users, 1H), 6,94-7,05 (m, 6H), 7,18 (users, 1H), to 7.67 (m, 1H).

Table 7-1
Example	The structural formula	1H-NMR (CDCl3) δ
42		a 1.08 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.9 Hz, 3H), of 2.33 (s, 3H), 3.33 and (sq, J=6,9 Hz, 1H), 3,37 (sq, J=7,0 Hz, 2H), to 3.67 (t, J=5,1 Hz, 2H), a 4.03 (d, J=14,7 Hz, 1H), 4,11 (d, J=14,7 Hz, 1H), 4,18-4,32 (m, 2H), 5,62 (users, 1H), 6.87 in-7,00 (m, 4H), 7,09-7,16 (m, 2H), 7,26 (users, 1H), 7,65 (d, J=9.4 Hz, 1H).
43		a 1.08 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.9 Hz, 3H), 3,34 (sq, J=6,9 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,69 (t, J=5.0 Hz, 2H), Android 4.04 (d, J=14,7 Hz, 1H), 4,13 (d, J=14,7 Hz, 1H), 4,19 is 4.36 (m, 2H), 5,75 (users, 1H), 6,94? 7.04 baby mortality (m, 4H), 7,13-7,20 (m, 2H), 7,25 (users, 1H), 7,69 (d, J=8.6 Hz, 1H).
44		of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), and 2.27 (users, 1H), 3,34 (sq, J=7,0 Hz, 1H), 3,39 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,14 (d, J=14,8 Hz, 1H), 4,23-of 4.35 (m, 2H), 5,80 (users, H), 6,51-only 6.64 (m, 2H), 6,92-was 7.08 (m, 2H), 7,21 (users, 1H), 7,72 (d, J=8.6 Hz, 1H).
45		a 1.08 (t, J=7.0 Hz, 3H), of 1.42 (d, J=6.9 Hz, 3H), 1,94 (users, 1H), 3,34 (sq, J=6,9 Hz, 1H), 3,39 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,14 (d, J=14,8 Hz, 1H), 4,20-4,37 (m, 2H), 5,63 (users, 1H), 6,95-7,03 (m, 3H), was 7.08 (d, J=1.8 Hz, 1H), 7,19 (users, 1H), 7,55-7,63 (m, 2H), 7,74 (d, J=8,8 Hz, 1H).

Table 7-2
46		a 1.08 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 2,32 (users, 1H), 3,34 (sq, J=7,0 Hz, 1H), 3,39 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5,1 Hz, 2H), 4,05 (d, J=14,7 Hz, 1H), 4,14 (d, J=14,7 Hz, 1H), 4,20-4,37 (m, 2H), 5,64 (users, 1H), 6,97-was 7.08 (m, 4H), 7,22 (users, 1H), 7,56 (userd, J=8,4 Hz, 2H), 7,72 (d, J=8.6 Hz, 1H).
47		to 1.14 (t, J=7.0 Hz, 3H), of 1.39 (d, J=7,0 Hz, 3H), of 1.99 (m, 2H), 3,28-to 3.41 (m, 5H), 3,99 (d, J=14.6 Hz, 1H), 4,05 (d, J=14.6 Hz, 1H), 4,18 (t, J=7,0 Hz, 2H), 5,41 (users, 1H), of 6.71-7,02 (m, 6H), 7,16 (users, 1H), 7,63 (d, J=8.6 Hz, 1H).

Table 8-1
Example	The structural formula	1H-NMR (CDCl3) the
48		of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 3,39 (sq, J=7,0 Hz, 2H), 3,69 (t, J=5,1 Hz, 2H), Android 4.04 (d, J=14,8 Hz, 1H), 4,12 (d, J=14,8 Hz, 1H), 4,20-to 4.33 (m, 2H), 5,43 (user., 1H), of 6.71 (m, 1H), 6,80 (m, 1H), 6,95-7,00 (m, 2H), 7,10 (sq, J=9.0 Hz, 1H), 7,22 (user., 1H), 7,69 (d, J=8,3 Hz, 1H).
49		a 1.08 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5.0 Hz, 2H), a 4.03 (d, J=14,8 Hz, 1H), 4,11 (d, J=14,8 Hz, 1H), 4,18-4,32 (m, 2H), 5,41 (user., 1H), 6,83 (m, 1H), 6,91-7,05 (m, 4H), 7,22 (user., 1H), the 7.65 (m, 1H).
50		to 1.21 (s, 3H), of 1.29 (s, 3H), of 1.33 (d, J=6.9 Hz, 3H), 3,35 (sq, J=6,9 Hz, 1H), Android 4.04 (d, J=a 13.9 Hz, 1H), 4,10 (s, 2H), 4,11 (d, J=a 13.9 Hz, 1H), by 5.87 (users, 1H), 6,91-7,05 (m, 6H), 7,09 (users, 1H), 7,63 (d, J=9,3 Hz, 1H).
51		of 1.40 (d, J=7,0 Hz, 3H), of 1.55 (m, 1H), 1,77-of 1.94 (m, 2H), 1,97-2,12 (m, 2H), 3,34 (sq, J=7,0 Hz, 1H), 3,65-a 3.83 (m, 2H), 3.96 points-4,27 (m, 5H), 5,67 (users, 1H), 6,91-7,06 (m, 6H), 7,24 (users, 1H), 7,66 (DD, J=8,4, 0.6 Hz, 1H).

Table 8-2
52
53		of 1.09 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 3,34 (sq, J=7,0 Hz, 1H), 3,39 (sq, J=7,0 Hz, 2H), 3,69 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,19 is 4.35 (m, 2H), 5,44 (user., 1H), 6,64-for 6.81 (m, 3H), 6,98-7,06 (m, 2H), 7,20-7,30 (m, 2H), 7,71 (d, J=8,4 Hz, 1H).

Table 9-1
Example	The structural formula	1H-NMR (CDCl3) δ
54		of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.8 Hz, 3H), 3.33 and (sq, J=6,8 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5,2 Hz, 2H), a 4.03 (d, J=14,7 Hz, 1H), 4,12 (d, J=14,7 Hz, 1H), 4,16-4,32 (m, 2H), 5,41 (users, 1H), 6,93-7,05 (m, 6H), 7.23 percent (users, 1H), to 7.67 (m, 1H).
55		of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 3,39 (sq, J=7,0 Hz, 2H), 3,69 (t, J=5.0 Hz, 2H), Android 4.04 (d, J=14,8 Hz, 1H), 4,12 (d, J=14,8 Hz, 1H), 4,19-4,34 (m, 2H), 5,35 (user., 1H), 6,79-7,13 (m, 4H), 7,20 (user., 1H), 7,69 (d, J=8.6 Hz, 1H).
56		of 1.41 (d, J=6.8 Hz, 3H), 1,50 is 2.10 (m, 4H), 3,32 (sq, J=6,8 Hz, 1H), 3,66-a-3.84 (m, 2H), 4,01-to 4.23 (m, 5H), 5,44 (user., 1H), 6,93-7,05 (m, 6H), 7,25 (m, 1H), 7,66 (d, J=6,4 Hz, 1H).
57		a 1.08 (t, J=7.0 Hz, 3H), of 1.42 (d, J=6.8 Hz, 3H), 3,34 (sq, J=6,8 Hz, 1H), 3,39 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5,1 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,20 is 4.35 (m, 2H), 5,47 (user., 1H), 6,39 (m, 1H), 6,65 (m, 1H), 7,01 (DD, J=8,8, 2.4 Hz, 1H), was 7.08 (d, J=2.4 Hz, 1H), 7,20 (user., 1H), 7,72 (d, J=8,8 Hz, 1H).

Table 9-2
58		a 1.08 (t, J =7.0 Hz, 3H), of 1.41 (d, J=6.8 Hz, 3H), 3.33 and (sq, J=6,8 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,69 (t, J=5.0 Hz, 2H), a 4.03 (d, J=14,8 Hz, 1H), 4,12 (d, J=14,8 Hz, 1H), 4,19-4,34 (m, 2H), 5,52 (user., 1H), 6,72 (m, 1H), 6.87 in? 7.04 baby mortality (m, 4H), 7.23 percent (OSiR., 1H), 7,68 (d, J=8.6 Hz, 1H).

Referential example 8:

To a solution of compound (0,22 g, 0.66 mmol)obtained in Reference example 6 in tetrahydrofuran (3 ml) was added tribromide phosphorus (0.18 g, 0.66 mmol) under cooling with ice. After stirring for 1 hour to the mixture was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate, dried over magnesium sulfate and concentrated when s is low pressure. Concentrate directly used for the next reaction.

¹H-NMR (CDCl₃) δ a 1.08 (t, J=7.0 Hz, 3H), 3,39 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5,1 Hz, 2H), 4,37 (t, J=5,1 Hz, 2H), to 4.81 (s, 2H), 6,95-7,05 (m, 6H), of 7.69 (m, 1H).

Example 59: N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate

To a solution of compound (107 mg, 0.27 mmol)obtained in Reference example 8 in acetonitrile (3 ml) was added diisopropylethylamine (0.10 ml, 0.55 mmol) and N-(2,4-dimethoxybenzyl)alaninate (97,7 mg, 0.41 mmol). After stirring at 50°C for 5 hours to the mixture was added an aqueous solution of sodium bicarbonate and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. To the mixture was added triperoxonane acid (3 ml) and the mixture is again stirred at 50°C for 2 hours, neutralized using aqueous sodium hydroxide solution and was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was recrystallized from chloroform/2-propanol to obtain the desired product (75 mg, 70%).

¹H-NMR (CDCl₃) δ a 1.08 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.8 Hz, 3H), 3.33 and-to 3.41 (m, 3H), 3,68 (t, J=5,1 Hz, 2H), a 4.03 (d, J=14.6 Hz, 1H), 4,12 (d, J=14.6 Hz, 1H), 4,23-4,27 (m, 2H), 5,58 (users, 1H), 6,94-7,05 (m, 6H), 7,24 (users, 1H), to 7.67 (m, 1H).

Examples 6-65:

Connection Examples 60-65 presented in Table 10 were obtained in the same manner as in Reference examples 1-4, 8 and Example 59, from 2,4-deformirovannoe and using commercially available or known compounds.

Table 10-1
Example	The structural formula	1H-NMR (CDCl3) δ
60		of 1.41 (d, J=7,0 Hz, 3H), 3,26 (s, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 3,65 (t, J=4.9 Hz, 2H), was 4.02 (d, J=14.6 Hz, 1H), 4,10 (d, J=14.6 Hz, 1H), 4,22-to 4.28 (m, 2H), 5,34 (users, 1H), 6,94-7,05 (m, 6H), 7,25 (users, 1H), to 7.67 (m, 1H),
61		of 1.02 (d, J=6.2 Hz, 6H), 3,40-of 3.48 (m, 3H), 3,68 (t, J=5,1 Hz, 2H), 4,10 (s, 2H), 4,24 (t, J=5,1 Hz, 2H), 5,45 (users, 1H), 6,94-7,05 (m, 6H), 7,21 (users, 1H), to 7.67 (m, 1H),
62		a 1.01 (d, J=6.0 Hz, 6H), of 1.41 (d, J=7,0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 3.43 points (m, 1H), to 3.67 (t, J=5,1 Hz, 2H), Android 4.04 (d, J=14,8 Hz, 1H), 4,12 (d, J=14,8 Hz, 1H), 4,22 (m, 2H), 5,33 (users, 1H), 6,93-7,05 (m, 6H), 7,26 (users, 1H), to 7.67 (m, 1H),
63		of 3.25 (s, 3H), 3,40 (s, 2H), to 3.64 (t, J=5.0 Hz, 2H), 4,08 (s, 2H), 4.26 deaths (t, J=5.0 Hz, 2H), 6,34 (users, 1H), 6,93? 7.04 baby mortality (m, 6H), 7,21 (users, 1H), 7,65 (m, 1H),
64		of 1.42 (d, J=7,0 Hz, 3H), 2,02 (Quint., J=6,7 Hz, 2H), or 3.28 (s, 3H), 3.27 to 3,37 (m, 3H), 4,01 (d, J=14.6 Hz, 1H), 4,07 (d, J=14.6 Hz, 1H), 4,19 (t, J=6,7 Hz, 2H), are 5.36 (users, 1H), 6,93-7,05 (m, 6H), 7,21 (users, 1H), 7,66 (d, J=8,8 Hz, 1H).

Table 10-2
65		1,82-to 1.87 (m, 2H), 2,43-to 2.57 (m, 2H), 3.43 points (s, 2H), 3,51-3,59 (m, 2H), 4,11 (s, 2H), 4,14-4,19 (m, 2H), 4,49 (m, 1H), 5,46 (users, 1H), 6,80 (users, 1H), 6,91-7,05 (m, 5H), 7,25 (d, J=2.0 Hz, 1H), to 7.67 (d, J=8,8 Hz, 1H).

Referential example 9:

The target product was obtained in the same manner as in Reference examples 1, 3 and 4, from 2-fluoro-4-bromonitromethane.

¹H-NMR (CDCl₃) δ of 1.12 (t, J=7.0 Hz, 3H), 3.43 points (sq, J=7,0 Hz, 2H, in), 3.75 (t, J=5,1 Hz, 2H), 4,37 (t, J=5,1 Hz, 2H), 4,88 (s, 2H), was 7.36 (DD, J=8,6, 1.8 Hz, 1H), 7,49 (d, J=1.8 Hz, 1H), to 7.59 (d, J=8.6 Hz, 1H).

Reference example 10:

The target product was obtained in the same manner as in Reference example 5, from compound obtained in Reference example 9.

¹H-NMR (CDCl₃) δ of 1.02 (t, J=7.0 Hz, 3H), 3,35 (sq, J=7,0 Hz, 2H), 3,71 (t, J=5,1 Hz, 2H), with 4.64 (t, J=5,1 Hz, 2H), 7,41 (m, 1H), 7.68 per-7,73 (m, 2H), of 10.05 (s, 1H).

Referential example 11:

To a solution of (4:1, 15 ml) of the compound (200 mg, 0.67 mmol)obtained in Reference example 10, in a mixed solvent of dioxane-water was added potassium carbonate (280 mg, 2.02 mmol), phenylboronic acid (123 mg, 1.01 mmol) and tetrakis(triphenylphosphine)palladium (154 mg, 0.13 mmol) and the mixture was heated to 110°C. After boiling under reflux for 2 hours, to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified on a column of silica gel (hexane:ethyl acetate=90:10-75:25 to 50:50) to obtain the target product (115 mg, 58%).

¹H-NMR (CDCl₃) δ of 1.07 (t, J=7.0 Hz, 3H), 3,42 (sq, J=7,0 Hz, 2H), 3,81 (t, J=5,1 Hz, 2H), to 4.81 (t, J=5,1 Hz, 2H), 7,39 (m, 1H), of 7.48 (t, J=7,6 Hz, 2H), 7,63-to 7.67 (m, 3H), 7,76 (m, 1H), of 7.96 (d, J=8.6 Hz, 1H), 10,11 (, 1H).

Example 66:N²-{[1-(2-ethoxyethyl)-6-phenyl-1H-benzimidazole-2-yl]methyl}glycinamide

Target product (31 mg, 38%) was obtained in the same manner as in Example 2 from the compound obtained in Reference example 11 (68 mg, 0.23 mmol).

¹H-NMR (CDCl₃) δ a 1.08 (t, J=7,1 Hz, 3H), 3,38 (sq, J=7,1 Hz, 2H), 3,41 (s, 2H, in), 3.75 (t, J=5,1 Hz, 2H), 4,11 (s, 2H), 4,35 (t, J=5,1 Hz, 2H), 5,68 (users, 1H), 7,22 (users, 1H), 7,33 (m, 1H), 7,42-7,51 (m, 4H), to 7.61-7,63 (m, 2H), 7,76 (m, 1H).

Examples 67-73:

Connection Examples 67-73 presented in Table 11 and Table 12 were obtained in the same manner as in Reference examples 9-11 and Example 66.

Table 11
Example	The structural formula	1H-NMR (CDCl3) δ
67		of 1.03 (t, J=7,1 Hz, 3H), 3,29 (sq, J=7,1 Hz, 2H), 3,36 (s, 2H), 3,70 (t, J=5,1 Hz, 2H), 4,06 (s, 2H), 4,30 (t, J=5,1 Hz, 2H), 5,68 (users, 1H), 7,05-to 7.09 (m, 2H), 7,16 (users, 1H), 7,37-7,39 (m, 2H), 7,49-7,53 (m, 2H), of 7.70 (m, 1H).
68		a 1.08 (t, J=7,1 Hz, 3H), of 1.39 (d, J=6.8 Hz, 3H), 3,32 (sq, J=6,8 Hz, 1H), 3,37 (sq, J=7,1 Hz, 2H), of 3.73 (t, J=5.0 Hz, 2H), Android 4.04 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), or 4.31 (dt, J=15,9, 5.0 Hz, 1H), 4,36 (dt, J=15,9, 5.0 Hz, 1H), 5,61 (users, 1H), 7,10-7,14 (m, 2H), 7,25 (users, 1H), 7,41-the 7.43 (m, 2H), 7,54-EUR 7.57 (m, 2H), 7,74 (m, 1H).
69		a 1.08 (t, J=7.0 Hz, 3H), of 1.39 (d, J=6.9 Hz, 3H), 3,30 (sq, J=6,9 Hz, 1H), 3,37 (sq, J=7,0 Hz, 2H), of 3.73 (t, J=4,8 Hz, 2H), Android 4.04 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,28-to 4.38 (m, 2H), 5,73 (users, 1H), 7,28 (users, 1H), 7,33 (m, 1H), 7,41-to 7.50 (m, 4H), 7,60-7,63 (m, 2H), to 7.75 (m, 1H.
70		of 1.10 (t, J=7.0 Hz, 3H), 3,40 (sq, J=7,0 Hz, 2H), 3,44 (s, 2H, in), 3.75 (t, J=5.0 Hz, 2H), 4,14 (s, 2H), 4,36 (t, J=5.0 Hz, 2H), ceiling of 5.60 (users, 1H), 7,27 was 7.36 (m, 4H), 7,40-the 7.43 (m, 2H), 7,50 (m, 1H), 7,78 (m, 1H).

Table 12
71		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 3,35 (sq, J=7,0 Hz, 1H), 3,39 (sq, J=7,0 Hz, 2H), 3,74 (t, J=5.0 Hz, 2H), 4,07 (d, J=14,7 Hz, 1H), 4.16 the (d, J=14,7 Hz, 1H), 4,30 (dt, J=15,0, 5.0 Hz, 1H), 4,37 (dt, J=15,0, 5.0 Hz, 1H), 5,81 (users, 1H), 7,26 and 7.36 (m, 4H), 7,39-7,42 (m, 2H), 7,50 (m, 1H), 7,78 (m, 1H).
72		of 1.10 (t, J=7.0 Hz, 3H), 3,40 (sq, J=7,0 Hz, 2H), 3.43 points (s, 2H), of 3.77 (t, J=5,1 Hz, 2H), 4,13 (s, 2H), to 4.38 (t, J=5,1 Hz, 2H), 5,65 (users, 1H), 7,21 (users, 1H), 7,41-7,49 (m, 4H), 7,54-7,58 (m, 2H), 7,78 (m, 1H).
73		of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,35 (sq, J=7,0 Hz, 1H), 3,40 (sq, J=7,0 Hz, 2H), 3,76 (t, J=5.0 Hz, 2H), 4,06 (d, J=14,7 Hz, 1H), 4.16 the (d, J=14,7 Hz, 1H), or 4.31-of 4.44 (m, 2H), 5,81 (users, 1H), 7,28 (users, 1H), 7,40-7,47 (m, 4H), 7,53-EUR 7.57 (m, 2H), 7,78 (m, 1H).

Reference example 12:

In nitrogen atmosphere, to a solution is soedineniya (150 mg, 0.5 mmol)obtained in Reference example 9, N-methylpyrrolidinone (5 ml) was added cesium carbonate (489 mg, 1.5 mmol), 4-tert-butylphenol (225 mg, 1.5 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (52 μl, 0.25 mmol) and copper chloride(I) (50 mg, 0.5 mmol) and the mixture was heated to 120°C. After stirring for 6 hours the reaction mixture was added 2 mol/l hydrochloric acid under ice cooling and the mixture was extracted with ethyl acetate. The organic layer was washed using 0.5 mol/l hydrochloric acid 2 mol/l aqueous sodium hydroxide solution, water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified on a column of silica gel (hexane:ethyl acetate=100:0-0:100) to give the desired product (56 mg, 30%).

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.32 (s, 9H), 3,41 (sq, J=7,0 Hz, 2H), and 3.72 (t, J=5,1 Hz, 2H), 4,35 (t, J=5,1 Hz, 2H), 4,89 (s, 2H), 6.89 in-7,02 (m, 4H), 7,31 and 7.36 (m, 2H), to 7.64 (d, J=8.5 Hz, 1H).

Example 74:N²-{[6-(4-tert-butylphenoxy)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Reference example 5 and Example 1 from the compound obtained in Reference example 12.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.32 (s, 9H), of 1.41 (d, J=6.9 Hz, 3H), 3,34 (sq, J=6,9 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5,1 Hz, 2H), Android 4.04 (d, J=14,9 Hz, 1H), 4,12 (q, j =14,9 Hz, 1H), 4,18-4,34 (m, 2H), 5,47 (users, 1H), 6.89 in-to 6.95 (m, 2H), 6,97-7,02 (m, 2H), 7,29 (users, 1H), 7,31 and 7.36 (m, 2H), to 7.67 (d, J=8.5 Hz, 1H).

Reference example 13:

To a solution of the compound (1.20 g, 4 mmol)obtained in Reference example 9, in N,N-dimethylformamide (15 ml) was added imidazole (1,36 g, 20 mmol) and tert-butyldimethylsilyl (904 mg, 6 mmol). After stirring at room temperature for 2 hours to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified on a column of silica gel (hexane:ethyl acetate=100:0-85:15) to obtain the target product (1.65 g, 100%).

¹H-NMR (CDCl₃) δ of 0.11 (s, 6H), of 0.91 (s, 9H), of 1.12 (t, J=7.0 Hz, 3H), 3,41 (sq, J=7,0 Hz, 2H), 3,74 (t, J=5.5 Hz, 2H), of 4.44 (t, J=5.5 Hz, 2H), 4,99 (s, 2H), 7,34 (DD, J=1,9, 8.5 Hz, 1H), 7,56 to 7.62 (m, 2H).

Reference example 14:

In a nitrogen atmosphere to a solution of compound (207 mg, 0.5 mmol)obtained in Reference example 13, N-methylpyrrolidinone (5 ml) was added cesium carbonate (489 mg, 1.5 mmol), 4-methoxyphenol (186 mg, 1.5 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (52 μl, 0.25 mmol) and copper chloride(I) (50 mg, 0.5 mmol) and the mixture was heated to 120°C. After stirring for 4 hours the reaction mixture was added 2 mol/l chlorotoluron the acid under ice cooling and the mixture was extracted with ethyl acetate. The organic layer was washed using 0.5 mol/l hydrochloric acid 2 mol/l aqueous sodium hydroxide solution, water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified on a column of silica gel (hexane:ethyl acetate=100:0-0:100) to give the desired product (36 mg, 21%).

¹H-NMR (CDCl₃) δ of 1.10 (t, J=7.0 Hz, 3H), 3,41 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5.0 Hz, 2H), 3,81 (s, 3H), 4,32 (t, J=5.0 Hz, 2H), 4,88 (s, 2H), 6,84-7,01 (m, 6H), 7,63 (d, J=8,8 Hz, 1H).

Example 75:N²-{[1-(2-ethoxyethyl)-6-(4-methoxyphenoxy)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Reference example 5 and Example 1 from the compound obtained in Reference example 14.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.8 Hz, 3H), 3.33 and (sq, J=6,8 Hz, 1H), 3,37 (sq, J=7,0 Hz, 2H), to 3.67 (t, J=5,1 Hz, 2H), 3,81 (s, 3H), a 4.03 (d, J=14,7 Hz, 1H), 4,10 (d, J=14,7 Hz, 1H), 4,17-4,30 (m, 2H,), 5,32 (users, 1H), 6,85-7,00 (m, 6H), 7,27 (users, 1H), to 7.64 (d, J=8,8 Hz, 1H).

Reference example 15:

To a solution of 3-fluoro-4-NITROPHENOL (2.5 g, 16.0 mmol) in N,N-dimethylformamide (30 ml) was added potassium carbonate (3.3 g, 24,0 mmol) and benzylbromide (2.1 ml, 17.6 mmol) and the mixture was heated at 70°C. After stirring for 1 hour to the mixture was added water and the mixture was extracted with ethyl acetate. Organic clomipraminum saturated salt solution, was dried over magnesium sulfate and concentrated under reduced pressure and the resulting residue is directly used for the next reaction.

¹H-NMR (CDCl₃) δ 5,14 (s, 2H), 6,79-6,86 (m, 2H), 7,38-the 7.43 (m, 5H), 8,10 (m, 1H).

Reference example 16:

The target product was obtained in the same manner as in Reference examples 1 and 3-5, from the compound obtained in Reference example 15.

¹H-NMR (CDCl₃) δ a 1.08 (t, J=7.0 Hz, 3H), 3,40 (sq, J=7,0 Hz, 2H), of 3.77 (t, J=5,1 Hz, 2H), 4,71 (t, J=5,1 Hz, 2H), further 5.15 (s, 2H),? 7.04 baby mortality (d, J=2.4 Hz, 1H), 7,11 (DD, J=9,0, 2.4 Hz, 1H), 7,35-7,49 (m, 5H), 7,79 (d, J=9,0 Hz, 1H), 10,01 (s, 1H).

Example 76:N²-{[6-(benzyloxy)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 2 from the compound obtained in Reference example 16, and the hydrochloride of (L)-alaninemia.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.39 (d, J=7,0 Hz, 3H), 3,32 (sq, J=7,0 Hz, 1H), 3,37 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5,1 Hz, 2H), 4.00 points (d, J=14.6 Hz, 1H), 4.09 to (d, J=14.6 Hz, 1H), 4,16-4,32 (m, 2H), 5,11 (s, 2H,), 5,75 (users, 1H), 6.87 in (d, J=2.2 Hz, 1H), 6,98 (DD, J=8,8, 2.2 Hz, 1H), 7,27-7,53 (m, 6H), to 7.61 (d, J=8,8 Hz, 1H).

Example 77:N²-{[6-(benzyloxy)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-2-methylalanine

The target product was obtained in the same manner as in Example 2 from the compound obtained in the Reference p is the iMER 16, and 2-methylalanine.

¹H-NMR (CDCl₃) δ of 1.10 (t, J=7.0 Hz, 3H), 1,45 (s, 6H), 3,37 (sq, J=7,0 Hz, 2H), 3,69 (t, J=5,1 Hz, 2H), 4.00 points (s, 2H), 4,24 (t, J=5,1 Hz, 2H), 5,12 (s, 2H), 5,47 (users, 1H), 6,86 (d, J=2.4 Hz, 1H), 6,98 (DD, J=8,8, 2,4 Hz, 1H), 7,31-of 7.48 (m, 5H), 7,51 (users, 1H), 7.62mm (d, J=8,8 Hz, 1H).

Reference example 17:

The target product was obtained in the same manner as in Reference examples 15, 1 and 3-5 from 3-fluoro-4-NITROPHENOL.

¹H-NMR (CDCl₃) δ of 1.07 (t, J=7.0 Hz, 3H), 3,40 (sq, J=7,0 Hz, 2H), 3,78 (t, J=5.3 Hz, 2H), 4,71 (t, J=5.3 Hz, 2H), 5,10 (s, 2H), 7,03 (d, J=2.2 Hz, 1H), 7,07-7,13 (m, 3H), 7,42-7,47 (m, 2H), 7,79 (d, J=9.0 Hz, 1H), 10,01 (s, 1H).

Example 78:N²-({1-(2-ethoxyethyl)-6-[(4-terbisil)oxy]-1H-benzimidazole-2-yl}methyl)-L-alaninate

The target product was obtained in the same manner as in Example 2 from the compound obtained in Reference example 17, and hydrochloride (L)-alaninemia.

¹H-NMR (CDCl₃) δ of 1.10 (t, J=7.0 Hz, 3H), of 1.40 (d, J=7,0 Hz, 3H), 3,32 (sq, J=7,0 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5,1 Hz, 2H), 4,01 (d, J=14.6 Hz, 1H), 4.09 to (d, J=14.6 Hz, 1H), 4,20-4,32 (m, 2H), to 5.08 (s, 2H,), 5,39 (users, 1H), 6,86 (d, J=2.2 Hz, 1H), of 6.96 (DD, J=8,8, 2.2 Hz, 1H), 7,06-7,10 (m, 2H), 7,25 (users, 1H), 7,42 was 7.45 (m, 2H), 7.62mm (d, J=8,8 Hz, 1H).

Reference example 18:

To a solution of 2,6-dichloro-3-nitropyridine (3.0 g, a 15.5 mmol) in dioxane (50 ml) was added potassium carbonate (2.4 g, 17,0 mmol) and 2-amoxicillin (1.4 g of 17.0 mmol) and the mixture was stirred at 50°. After stirring for 3 hours to the mixture was added potassium carbonate (1.8 g, 13,0 mmol) and 2-amoxicillin (0.9 g, 10.0 mmol) and the mixture was stirred at 50°C for 3 hours. To the reaction mixture were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (ethyl acetate:hexane=1:5) to obtain the target product (3.4 g, 89%).

¹H-NMR (CDCl₃) δ 1,24 (t, J=7.0 Hz, 3H), 3,57 (sq, J=7,0 Hz, 2H), to 3.67 (t, J=5,2 Hz, 2H), 3,82 (sq, J=5,2 Hz, 2H), is 6.61 (d, J=8.5 Hz, 1H), 8,35 (d, J=8.5 Hz, 1H), 8,59 (user., 1H).

Reference example 19:

The target product was obtained in the same manner as in Reference example 2 from the compound obtained in Reference example 18.

¹H-NMR (CDCl₃) δ of 1.18 (t, J=7.0 Hz, 3H), 3,39-to 3.50 (m, 6H), of 6.20 (d, J=9.0 Hz, 1H), 7,12-7,17 (m, 2H), 7,25 (m, 1H), 7,37-7,44 (m, 2H), 8,42 (d, J=9.0 Hz, 1H), 8,66 (user., 1H).

Reference example 20:

The target product was obtained in the same manner as in Reference examples 3-5, from the compound obtained in Reference example 19.

¹H-NMR (CDCl₃) δ is 1.01 (t, J=7.0 Hz, 3H), 3,38 (sq, J=7,0 Hz, 2H), and 3.72 (t, J=5.6 Hz, 2H), 4,70 (t, J=5.6 Hz, 2H), 6,98 (d, J=8,8 Hz, 1H), 7,17-7,28 (m, 3H), 7,37-7,46 (m, 2H), 8,16 (d, J=8,8 Hz, 1H), 10,00 (s, 1H).

Example 79:N²-{[3-(2-ethoxyethyl)-5-Fenox is-3H-imidazo[4,5-b]pyridine-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 1 from the compound obtained in Reference example 20.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,35 (sq, J=7,0 Hz, 1H), 3,38 (sq, J=7,0 Hz, 2H), 3,71 (t, J=5,1 Hz, 2H), 4,06 (d, J=to 15.0 Hz, 1H), 4,14 (d, J=to 15.0 Hz, 1H), 4,32 (t, J=5,1 Hz, 2H), 5.56mm (users, 1H), to 6.67 (d, J=8.6 Hz, 1H), 7,11-7,21 (m, 3H), 7,26 (users, 1H), 7,35-7,42 (m, 2H), 7,95 (d, J=8.6 Hz, 1H).

Example 80:N²-{[3-(2-ethoxyethyl)-5-phenoxy-3H-imidazo[4,5-b]pyridine-2-yl]methyl}glycinamide

The target product was obtained in the same manner as in Example 2 from the compound obtained in Reference example 20.

¹H-NMR (CDCl₃) δ a 1.08 (t, J=7.0 Hz, 3H), 3,38 (sq, J=7,0 Hz, 2H), 3,42 (s, 2H), and 3.72 (t, J=4.9 Hz, 2H), 4,12 (s, 2H), 4,33 (t, J=4.9 Hz, 2H), 5,73 (users, 1H), 6,76 (d, J=8,4 Hz, 1H), 7,11-7,22 (m, 3H), 7,26 (users, 1H), 7,35-7,42 (m, 2H), 7,95 (d, J=8,4 Hz, 1H).

Reference example 21:

The target product was obtained in the same manner as in Reference example 1, 2,4,5-cryptomaterial.

¹H-NMR (CDCl₃) δ 1,25 (t, J=7,1 Hz, 3H), 3.43 points (sq, J=5,1 Hz, 2H), 3,57 (sq, J=7,1 Hz, 2H), and 3.72 (t, J=5,1 Hz, 2H), 6,66 (DD, J=12,4, 6,6 Hz, 1H), with 8.05 (DD, J=10,2, 8.6 Hz, 1H), 8,29 (user., 1H).

Reference example 22:

The target product was obtained in the same manner as in Reference examples 2 to 5, from the compound obtained in Reference example 21.

¹H-YAM who (CDCl ₃) δ 0,99 (t, J=7.0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 2H), 3,71 (t, J=5,1 Hz, 2H), with 4.64 (t, J=5,1 Hz, 2H), 7,00-7,10 (m, 4H), 7,13 (d, J=7,1 Hz, 1H), 7,66 (d, J=10.3 Hz, 1H), 10,04 (s, 1H).

Example 81:N²-{[1-(2-ethoxyethyl)-5-fluoro-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 1 from the compound obtained in Reference example 22.

¹H-NMR (CDCl₃) δ of 1.07 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,32 (sq, J=7,0 Hz, 1H), 3,37 (sq, J=7,0 Hz, 2H), 3,66 (t, J=5,1 Hz, 2H), was 4.02 (d, J=14,7 Hz, 1H), 4,11 (d, J=14,7 Hz, 1H), 4,17-4,32 (m, 2H), 5,38 (users, 1H), 6,90-7,05 (m, 5H), 7,16 (users, 1H), 7,52 (d, J=12.1 Hz, 1H).

Reference example 23:

The target product was obtained in the same manner as in Reference examples 1-4, 2,4-deformirovannoe, 4-amino-(1-tert-butoxycarbonyl)piperidine and 4-terfenol.

¹H-NMR (CDCl₃) δ to 1.48 (s, 9H), 1.91 a-1,95 (m, 2H), 2,22-is 2.37 (m, 2H), was 2.76-of 2.93 (m, 2H), 4,30 (user., 2H), 4,60 (m, 1H), a 4.86 (s, 2H), 6,86-7,05 (m, 5H), 7,14 (d, J=2.0 Hz, 1H), 7,58 (d, J=8,8 Hz, 1H).

Reference example 24:

The target product was obtained in the same manner as in Reference example 5, from compound obtained in Reference example 23.

¹H-NMR (CDCl₃) δ to 1.48 (s, 9H), 1,89-of 1.93 (m, 2H), 2,23-of 2.38 (m, 2H), 2,85-to 2.94 (m, 2H), 4,33 (user., 2H), 5,63 (m, 1H), 6,99-7,10 (m, 5H), 7,18 (d, J=2.0 Hz, 1H), 7,86 (d, J=8,8 Hz, 1H), 10,04 (s, 1H).

Example 82:tert-butyl 4-[2-({[(2S)-1-amino-1-oxopropyl--yl]amino}methyl)-6-(4-pertenece)-1H-benzimidazole-1-yl]piperidine-1-carboxylate

The target product was obtained in the same manner as in Example 1 from the compound obtained in Reference example 24.

¹H-NMR (CDCl₃) δ to 1.38 (d, J=7,0 Hz, 3H), of 1.48 (s, 9H), 1,86-1,89 (m, 2H), 2,30-of 2.34 (m, 2H), 2,81-2,89 (m, 2H), 3,28 (sq, J=7,0 Hz, 1H), was 4.02 (d, J=14,7 Hz, 1H), 4,10 (d, J=14,7 Hz, 1H), or 4.31 was 4.42 (m, 3H), 6,02 (users, 1H), 6,87? 7.04 baby mortality (m, 6H), to 7.15 (d, J=2.0 Hz, 1H), to 7.64 (d, J=8,8 Hz, 1H).

Example 83:N²-{[6-(4-pertenece)-1-(piperidine-4-yl)-1H-benzimidazole-2-yl]methyl}-L-alaninate

To a solution of compound (68 mg, 0.13 mmol)obtained in Example 82, in dichloromethane (1.3 ml) was added triperoxonane acid (260 ml) and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added aqueous sodium hydroxide solution and the mixture was extracted with chloroform. The organic layer was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (ethyl acetate:methanol=99:1-80:20) to give the desired product (38 mg, 71%).

¹H-NMR (CDCl₃) δ of 1.41 (d, J=7,0 Hz, 3H), 1,86-1,89 (m, 2H), and 2.26-2.40 a (m, 2H), 2,72-of 2.81 (m, 2H), 3,26-to 3.33 (m, 3H), was 4.02 (d, J=14,7 Hz, 1H), 4,10 (d, J=14,7 Hz, 1H), 4,30 (m, 1H), of 5.89 (users, 1H), 6.89 in-7,07 (m, 6H), 7,33 (d, J=2.0 Hz, 1H), 7,65 (d, J=8,8 Hz, 1H).

Reference example 25:

To a solution of the compound (300 mg, of 0.68 mmol)obtained in alocrom example 24, in dichloromethane (6.8 ml) was added triperoxonane acid (1.4 ml) and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added aqueous sodium hydroxide solution and the mixture was extracted with chloroform. The organic layer was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was dissolved in dichloromethane (6.8 ml), to the mixture was added triethylamine (142 μl, of 1.02 mmol) and isopropylidene (100 μl, of 1.02 mmol) and the mixture was stirred at room temperature for 1 hour. To the reaction mixture were added water and the mixture was extracted with chloroform. The organic layer was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (chloroform:methanol=99:1-85:15) to obtain the target product (280 mg, 97%).

¹H-NMR (CDCl₃) δ of 1.18 (d, J=6.6 Hz, 6H), 1,92-of 1.97 (m, 2H), 2,28-to 2.42 (m, 2H), 2.91 in-a 3.01 (m, 2H), 4,01 (m, 1H), 4,12-4,17 (m, 2H), 4,33 (m, 1H), 5,65 (m, 1H), 6,97-7,10 (m, 5H), 7,20 (d, J=2.0 Hz, 1H), 7,86 (d, J=8,8 Hz, 1H), 10,04 (s, 1H).

Example 84:4-[2-({[(2S)-1-amino-1-oxoprop-2-yl]amino}methyl)-6-(4-pertenece)-1H-benzimidazole-1-yl]-N-(propan-2-yl)piperidine-1-carboxamide

The target product was obtained in the same manner as in Example 1 from the compound obtained in the Reference note is re 25.

¹H-NMR (CDCl₃) δ 1,17 (d, J=6.6 Hz, 6H), to 1.38 (d, J=7,0 Hz, 3H), 1,90-of 1.92 (m, 2H), 2,30-to 2.40 (m, 2H), 2,87-to 2.94 (m, 2H), 3.27 to (sq, J=7,0 Hz, 1H), 3,93-4,18 (m, 5H), 4,36 is 4.45 (m, 2H), 5,73 (users, 1H), 6.89 in-7,03 (m, 6H), 7,16 (d, J=2.0 Hz, 1H), 7,65 (d, J=8,8 Hz, 1H).

Example 85:N²-{[1-(1-acetylpiperidine-4-yl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Reference example 25 and Example 1 from the compound obtained in Reference example 24, and acetylchloride.

¹H-NMR (CDCl₃) δ to 1.38 (d, J=7,0 Hz, 3H), 1,89 is 2.46 (m, 3H), of 2.16 (s, 3H), to 2.67 (m, 1H), 3,18-of 3.32 (m, 2H), 3,65 (m, 1H), 3,99 is 4.13 (m, 3H), to 4.52 (m, 1H), 4,89 (m, 1H), 5,85 (users, 1H), 6,88-7,05 (m, 6H), 7,11 (d, J=2.0 Hz, 1H), 7,65 (d, J=8,8 Hz, 1H).

Example 86:N²-({6-(4-pertenece)-1-[1-(methylsulphonyl)piperidine-4-yl]-1H-benzimidazole-2-yl}methyl)-L-alaninate

The target product was obtained in the same manner as in Reference example 25 and Example 1 from the compound obtained in Reference example 24, and methanesulfonanilide.

¹H-NMR (CDCl₃) δ of 1.37 (d, J=6.8 Hz, 3H), 2.00 in of 2.16 (m, 3H), 2,48-2,61 (m, 2H), 2,88 (m, 1H), 2,86 (s, 3H), 3,25 (sq, J=6,8 Hz, 1H), 3,99-4,16 (m, 4H), to 4.46 (m, 1H), by 5.87 (users, 1H), for 6.81 (users, 1H), 6.89 in-7,05 (m, 5H), 7,21 (d, J=2.0 Hz, 1H), 7,65 (d, J=8,8 Hz, 1H).

Reference example 26:

To a solution of compound (2.28 g, 6,9 mmol)obtained in Reference example 7, in tetrahydrofuran (70 ml) to relax is whether the ethyl ester of (L)-alanine hydrochloride (2.15 g, 14 mmol), triethylamine (of 1.95 ml, 14 mmol) and sodium sulfate (10 g) and the mixture was stirred at room temperature. After stirring for 1 hour to the mixture was added cyanoborohydride sodium (503 mg, 8 mmol) and the mixture was stirred for 4 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with ethyl acetate. The organic layer was extracted, washed with water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (chloroform:methanol=100:0-95:5) to obtain the target product (1.78 g, 60%).

¹H-NMR (CDCl₃) δ a 1.08 (t, J=7.0 Hz, 3H), of 1.28 (t, J=7,1 Hz, 3H), of 1.35 (d, J=7,0 Hz, 3H), 3,38 (sq, J=7,0 Hz, 2H), 3,48 (sq, J=7,1 Hz, 1H), 3,70 (t, J=5.3 Hz, 2H), was 4.02 (d, J=a 13.9 Hz, 1H), 4,10-to 4.23 (m, 3H), or 4.31 was 4.42 (m, 2H), 6.90 to-7,05 (m, 6H), 7,66 (d, J=8.6 Hz, 1H).

Reference example 27:

To a solution of compound (2,79 g, 6.5 mmol)obtained in Reference example 26, in acetonitrile (65 ml) was added di-tert-BUTYLCARBAMATE (1.64 g, 7.5 mmol) and the mixture was stirred under heating at 60°C for 3 hours and at 100°C for 3 hours. After cooling to room temperature the mixture was concentrated under reduced pressure and the residue was purified on a column of silica gel (hexane:ethyl acetate=100:0-70:30) to obtain the target product (2.24 g, 65%).

¹H is the Mr (CDCl ₃) δ 1,00-of 1.18 (m, 6H), of 1.40 (d, J=7,1 Hz, 3H), of 1.44 (s, 9H), 3,38 (sq, J=7,0 Hz, 2H), 3,68 (t, J=5,9 Hz, 2H), 3,86-4,12 (m, 2H), 4,19-4,55 (m, 3H), and 4.75 (d, J=to 15.4 Hz, 1H), to 4.98 (d, J=to 15.4 Hz, 1H), 6.90 to-7,08 (m, 6H), to 7.64 (d, J=8,8 Hz, 1H).

Reference example 28:

To a solution of compound (2.24 g, 4.2 mmol)obtained in Reference example 27, in ethanol (40 ml) was added 2 mol/l aqueous sodium hydroxide solution of 4.2 ml, 8.4 mmol) in an ice bath. After stirring for 30 minutes under these conditions to the reaction mixture were added water and the aqueous layer was washed with simple ether. The aqueous layer was brought to pH 4 with 2 mol/l hydrochloric acid and the mixture was extracted with chloroform. The organic layer was extracted, washed with saturated saline solution and dried over sodium sulfate to obtain the target product (2,02 g, 96%).

¹H-NMR (CDCl₃) δ is 1.11 (t, J=7.0 Hz, 3H), 1,49 (s, 9H), of 1.55 (d, J=7.2 Hz, 3H), 3,30-to 3.50 (m, 2H), 3,63 of 3.75 (m, 2H), 3,90 (users, 1H), 4,13-the 4.29 (m, 2H), 4,54 (users, 1H), 5,27 (users, 1H), 6,91-was 7.08 (m, 6H), 7,63 (d, J=8.6 Hz, 1H).

Example 87:N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-N-(2-hydroxy-2-methylpropyl)-L-alaninate

To a solution of compound (53 mg, 0.1 mmol)obtained in Reference example 28, in dichloromethane (2 ml) was added 1-amino-2-methylpropan-2-ol (18 mg, 0.2 mmol) and PyBOP [registered trademark, hexaflurophosphate benzac eazol-1-yl-oxy-Tris(pyrrolidino)phosphonium (hexaphosphate benzotriazol-1-yl-oxy-Tris(pyrrolidino)phosphonium)] (52 mg, 0.1 mmol) and the mixture was stirred at room temperature. After 16 hours the reaction mixture was added 10% aqueous citric acid solution and the mixture was extracted with ethyl acetate. The organic layer was extracted, washed with water and saturated saline and dried over sodium sulfate. After concentration under reduced pressure the residue was purified on a column of silica gel (chloroform:methanol=100:0-98:2) to obtain the target product (51 mg, 89%). The product was dissolved in ethyl acetate (1 ml), to the mixture was added 4 mol/l solution of hydrogen chloride in ethyl acetate (1 ml, 4 mmol) and the mixture was stirred at room temperature. After 14 hours the mixture was concentrated under reduced pressure. To the obtained residue was added 2 mol/l aqueous sodium hydroxide solution and the mixture was extracted with chloroform. The organic layer was extracted, washed with saturated saline solution and dried over sodium sulfate. After concentration under reduced pressure the residue was purified on a column of silica gel (chloroform:methanol=100:0-95:5) to obtain the target product (32 mg, 76%).

¹H-NMR (CDCl₃) δ of 1.10 (t, J=7.0 Hz, 3H), of 1.29 (s, 6H), of 1.36 (d, J=6.8 Hz, 3H), 3,21 (DD, J= 5,3, 3.6 Hz, 1H), 3,29-3,51 (m, 4H), 3,61-to 3.73 (m, 2H), 3,97 (d, J=14,3 Hz, 1H), 4,11 (d, J=14,3 Hz, 1H), 4,21 (dt, J=15,3 and 4.2 Hz, 1H), 4,33 (m, 1H), 6.90 to-7,07 (m, 6H), to 7.68 (DD, J=8,3, 0.9 Hz, 1H), 7,83 (ushort, J=6.0 Hz, 1H).

Examples 88-90:

Connection Examples 8-90, presented in Table 13 were obtained in accordance with methods described in the above Reference examples and Examples, or similar methods.

Table 13
Example	The structural formula	1H-NMR (CDCl3) δ
88		a 1.08 (t, J=7.0 Hz, 3H), of 1.37 (d, J=7,0 Hz, 3H), 3,32 (sq, J=7,0 Hz, 1H), 3,35 (s, 3H), 3,38 (sq, J=7,0 Hz, 2H), 3.43 points-to 3.52 (m, 4H), to 3.67 (t, J=5,2 Hz, 2H), 3,99 (d, J=14,7 Hz, 1H), 4,08 (d, J=14,7 Hz, 1H), 4.26 deaths (t, J=5,2 Hz, 2H), 6,91-7,07 (m, 6H), 7,53 (users, 1H), of 7.64-of 7.69 (m, 1H).
89		a 1.08 (t, J=7,1 Hz, 3H), of 1.37 (d, J=6.8 Hz, 3H), 2,41 of $ 2.53 (m, 6H), of 3.25 to 3.45 (m, 5H), 3,62-and 3.72 (m, 6H), 4.00 points (d, J=14,9 Hz, 1H), 4,08 (d, J=14,9 Hz, 1H), 4,17-to 4.33 (m, 2H), 6,94-7,05 (m, 6H), of 7.48 (ushort, J=5,2 Hz, 1H), 7,66 (m, 1H).
90		a 1.08 (t, J=7,1 Hz, 3H), 1,19 (d, J=7,0 Hz, 3H), 3,31-of 3.43 (m, 3H), 3,44-of 3.80 (m, 10H), of 3.96 (d, J=14.1 Hz, 1H), 4,11 (d, J=14.1 Hz, 1H), 4,32 (m, 1H), 4,46 (m, 1H), 6.90 to-7,06 (m, 6H), 7,63 (d, J=8.6 Hz, 1H).

Reference example 29:

To a solution of alcohol (500 mg, was 1.58 mmol), extracting the aqueous in the same way, as in the Reference examples 1-4, in dichloromethane (16 ml) was added thionyl chloride (342 μl, 4,74 mmol) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and the obtained residue was dissolved in chloroform, to the mixture was added an aqueous solution of sodium hydroxide. The mixture was extracted with chloroform and the organic layer was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure to obtain the target product (508 mg, 96%).

¹H-NMR (CDCl₃) δ is 3.27 (s, 3H), to 3.67 (t, J=5,1 Hz, 2H), to 4.38 (t, J=5,1 Hz, 2H), 4.92 in (s, 2H), of 6.96-7,06 (m, 6H), 7,58 (d, J=8,4 Hz, 1H).

Example 91:N²-{[6-(4-pertenece)-1-(2-methoxyethyl)-1H-benzimidazole-2-yl]methyl}-2-methylalanine

To a solution of the compound (300 mg, 0.90 mmol)obtained in Reference example 29, in acetonitrile (4.5 ml) was added 2,2-dimethylglycine (138 mg, 1.35 mmol), diisopropylethylamine (321 μl, of 1.80 mmol) and sodium iodide (135 mg, 0.90 mmol) and the mixture was heated to 50°C and was stirred overnight. To the reaction mixture was added water, the mixture was extracted with chloroform and the organic layer was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (ethyl acetate:methanol=99:1-80:20) to obtain the target product (169 mg, 47%.

¹H-NMR (CDCl₃) δ 1,45 (s, 6H), 3,26 (s, 3H), 3,66 (t, J=5.0 Hz, 2H), 4.00 points (s, 2H), 4,25 (t, J=5.0 Hz, 2H), 5,57 (users, 1H), 6,94-7,05 (m, 6H), 7,46 (users, 1H), to 7.67 (m, 1H).

Reference example 30:

To a solution of compound (0.84 g, 2.8 mmol)obtained in Reference example 10, in N,N-dimethylformamide (30 ml) was added N-chlorosuccinimide (0.95 g, 7.1 mmol) and the mixture was heated to 40°C. After stirring over night the mixture was added water, the mixture was extracted with ethyl acetate and the organic layer was washed with saturated saline, dried over magnesium sulfate, concentrated under reduced pressure and directly used for the next reaction.

¹H-NMR (CDCl₃) δ of 1.07 (t, J=7.0 Hz, 3H), 3,39 (sq, J=7,0 Hz, 2H), 3,76 (t, J=5,1 Hz, 2H), 4.72 in (t, J=5,1 Hz, 2H), 8,01-8,02 (m, 2H), to 10.09 (s, 1H).

Reference example 31:

The target product was obtained in the same manner as in Reference example 11, from the compound obtained in Reference example 30.

¹H-NMR (CDCl₃) δ of 1.05 (t, J=7.0 Hz, 3H), 3,38 (sq, J=7,0 Hz, 2H), of 3.77 (t, J=5,1 Hz, 2H), amounts to 4.76 (t, J=5,1 Hz, 2H), 7,12-7,20 (m, 3H), 7,40-7,46 (m, 2H), 8,02 (s, 1H), 10,12 (s, 1H).

Example 92:N²-{[5-chloro-1-(2-ethoxyethyl)-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 1 from the compound obtained in Reference example is 31.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (t, J=7.0 Hz, 3H), 3,32-of 3.42 (m, 3H), 3,71 (t, J=5,1 Hz, 2H), 4,05 (d, J=14.6 Hz, 1H), 4,14 (d, J=14.6 Hz, 1H), 4,23-to 4.38 (m, 2H), 5,39 (users, 1H), 7,11-7,17 (m, 3H), 7,21 (users, 1H), 7,41 was 7.45 (m, 2H), 7,83 (s, 1H).

Examples 93-108:

Connection Examples 93-108, are presented in Tables 14-16, were obtained in accordance with methods described in the above Reference examples and Examples, or similar methods.

Table 14-1
Example	The structural formula	1H-NMR (CDCl3) δ
93		a 1.11 (t, J=7.0 Hz, 3H), USD 1.43 (d, J=7,0 Hz, 3H), 3,32 is-3.45 (m, 3H), 3,82 (t, J=5,1 Hz, 2H), 4,07 (d, J=14,9 Hz, 1H), 4,17 (d, J=14,9 Hz, 1H), 4,65-and 4.68 (m, 2H), 5,35 (users, 1H), 6.87 in? 7.04 baby mortality (m, 6H), 7,58 (d, J=8,8 Hz, 1H).
94		of 1.09 (t, J=7.0 Hz, 3H), 1,24 (d, J=7,0 Hz, 6H), of 1.41 (d, J=7,0 Hz, 3H), 2,90 (m, 1H), 3,31 is 3.40 (m, 3H), 3,68 (t, J=5,1 Hz, 2H), Android 4.04 (d, J=14,9 Hz, 1H), 4,11 (d, J=14,9 Hz, 1H), 4,20-the 4.29 (m, 2H), 5,33 (users, 1H), 6.90 to-6,99 (m, 4H), 7,16-7,19 (m, 2H), 7,26 (users, 1H), 7,66 (m, 1H).
95		of 1.09 (t, J=7.0 Hz, 3H) 1,41 (d, J=7,0 Hz, 3H), 2.06 to a 2.13 (m, 2H), 2,85-2,90 (m, 4H), 3,31 is 3.40 (m, 3H), 3,68 (t, J=5,1 Hz, 2H), a 4.03 (d, J=14.6 Hz, 1H), 4,11 (d, J=14.6 Hz, 1H), 4,18-4,30 (m, 2H), 5,33 (users, 1H), 6,79 (d, J=8,1 Hz, 1H), 6,86 (m, 1H), 6,97-of 6.99 (m, 3H), 7,15 (d, J=8,3 Hz, 1H), 7,65 (d, J=9,3 Hz, 1H).
96		to 1.38 (t, J=7,1 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 3,32 (sq, J=7,0 Hz, 1H), 3,99 (d, J=14,8 Hz, 1H), 4,06 (d, J=14,8 Hz, 1H), 4,06-4,16 (m, 2H), 5,50 (user., 1H), 6,88-7,00 (m, 4H), 7,09-7,16 (m, 3H), of 7.65 (m, 1H).

Table 14-2
97		of 1.40 (t, J=7,3 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 3,32 (sq, J=7,0 Hz, 1H), 4.00 points (d, J=to 15.0 Hz, 1H), 4,08 (d, J=to 15.0 Hz, 1H), 4.09 to-4,20 (m, 2H), 5,52 (user., 1H), of 6.71 (m, 1H), 6,80 (m, 1H), 6.87 in-to 7.15 (m, 4H), of 7.69 (d, J=8.6 Hz, 1H).

Table 15
Example	The structural formula	1H-NMR (CDCl3) δ
98		of 1.39 (t, J=7,1 Hz, 3H), of 1.42 (d, J=6.8 Hz, 3H), 3,31 (sq, J=6,8 Hz, 1H), 3,99 (d, J=14,8 Hz, 1H), 4,06 (d, J=14,8 Hz, 1H), 4,07-4,17 (m, 2H), 5,48 (user., 1H), 6,80 for 7.12 (m, 6H), the 7.65 (m, 1H),
99		0,95-1,05 (m, 2H), 1,13-of 1.23 (m, 2H), USD 1.43 (d, J=7,0 Hz, 3H), 3,18 (m, 1H), 3,30 (sq, J=7,0 Hz, 1H), 4,08 (d, J=14.4 Hz, 1H), 4,17 (d, J=14.4 Hz, 1H), 5,52 (user., 1H), 6,80-7,06 (m, 4H), 7,13 (d, J=2.4 Hz, 1H), 7.23 percent (OSiR., 1H), to 7.61 (d, J=8.6 Hz, 1H).
100		0,98-1,08 (m, 2H), 1,15-1,25 (m, 2H), 1,44 (d, J=6.8 Hz, 3H), 3,19 (m, 1H), 3,36 (sq, J=6,8 Hz, 1H), 4,10 (d, J=to 15.4 Hz, 1H), 4,18 (d, J=to 15.4 Hz, 1H), 5,44 (user., 1H), 6,93-7,00 (m, 3H), 7,14-7,26 (m, 4H), 7,66 (d, J=8.6 Hz, 1H).
101		of 1.20 (s, 3H), of 1.29 (s, 3H), 1,32 (d, J=6.9 Hz, 3H), of 2.33 (s, 3H), 3,34 (sq, J=6,9 Hz, 1H), a 4.03 (d, J=a 13.9 Hz, 1H), 4,07-to 4.14 (m, 3H), 5,91 (users, 1H), 6,84-6,91 (m, 2H), 6,94-of 6.99 (m, 2H), 7,08-to 7.15 (m, 3H), to 7.61 (m, 1H).
102		of 1.06 (t, J=7.0 Hz, 3H), 1,22 (t, J=7,6 Hz, 3H), 1,38 (d, J=6.8 Hz, 3H), 2,61 (sq, J=7,6 Hz, 2H), 3,30-to 3.38 (m, 3H), of 3.65 (t, J=5,1 Hz, 2H), a 4.03 (d, J=14.6 Hz, 1H), 4.09 to (d, J=14.6 Hz, 1H), 4,16-to 4.28 (m, 2H,), 5,41 (users, 1H), 6.89 in-of 6.96 (m, 4H), 7,11-7,13 (m, 2H), 7,21 (users, 1H), 7.62mm (m, 1H).

Table 16-1
Example	The structural formula	1H-NMR (CDCl3) δ
103		(CD3OD) of 1.24 (s, 3H), 1,25 (s, 3H), of 1.61 (d, J=7,1 Hz, 3H), 4,14 (sq, J=7,1 Hz, 1H), 4,27 (d, J=15.3 Hz, 1H), 4,32 (d, J=15.3 Hz, 1H), to 4.62 (d, J=15.1 Hz, 1H), 4,67 (d, J=15.1 Hz, 1H), 7,00-7,10 (m, 3H), 7,22-7,28 (m, 2H), 7,37 (d, J=2.0 Hz, 1H), 7,73 (d, J=8,8 Hz, 1H).
104		of 1.39 (t, J=7.0 Hz, 3H), USD 1.43 (d, J=7,0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 4.00 points (d, J=14,9 Hz, 1H), a 4.03 (d, J=14,9 Hz, 1H), 4,14 (sq, J=7,0 Hz, 2H), 5,63 (users, 1H), 6,94-7,03 (m, 4H), 7,09 (users, 1H), 7,12-7,21 (m, 2H), 7,69 (d, J=8.6 Hz, 1H).
105		(CD3OD) of 1.20 (s, 3H), 1,22 (s, 3H), of 1.30 (d, J=6.8 Hz, 3H), of 3.25 to 3.36 (m, 1H), a 4.03 (d, J=14,3 Hz, 1H), 4,11 (d, J=14,3 Hz, 1H), 4,18 (d, J=to 15.0 Hz, 1H), 4,25 (d, J=to 15.0 Hz, 1H), 6.87 in-of 6.96 (m, 2H), 7.03 is-to 7.18 (m, 3H), EUR 7.57 (d, J=8,8 Hz, 1H).
106		a 1.08 (t, J=7,1 Hz, 3H), 1,21 (d, J=7,0 Hz, 3H), 3,17-a-3.84 (m, 9H), 3,91 is 4.35 (m, 5H), of 4.45 (m, 1H), 6.73 x-7,07 (m, 7H), to 7.61 (t, J=8.6 Hz, 1H).

Table 16-2
107		a 1.08 (t, J=7.0 Hz, 3H), 1,23-of 1.32 (m, 3H), 2,82-of 4.54 (m, 16H), 6,88-was 7.08 (m, 6H), 7,63 (m, 1H).
108		a 1.08 (t, J=7.0 Hz, 3H), 1,13-of 1.23 (m, 3H), 2,28 (m, 1H), 2.57 m-of 3.46 (m, 6H), to 3.58-br4.61 (m, 9H), 6.90 to-7,06 (m, 6H), to 7.61 (m, 1H).

Reference example 32:

The target product was obtained in the same manner as in Reference example 1 from 4-bromo-2,5-deformirovannoe.

¹H-NMR (CDCl₃) δ of 1.23 (t, J=7.0 Hz, 3H), 3.43 points (sq, J=5,2 Hz, 2H), 3,56 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5,2 Hz, 2H), 7,11 (d, J=5,9 Hz, 1H), to 7.93 (d, J=8.6 Hz, 1H).

Reference example 33:

The target product was obtained in the same manner as in Reference example 3-2, from the compound obtained in Reference example 32.

¹H-NMR (CDCl₃) δ to 1.21 (t, J=7,3 Hz, 3H), 3,51-to 3.58 (m, 4H), of 3.65 (t, J=5,1 Hz, 2H), of 6.49 (d, J=9.5 Hz, 1H), 6,72 (d, J=6,6 Hz, 1H).

Reference example 34:

The target product was obtained in the same manner as in Reference example 4 from the compound obtained in Reference example 33.

¹H-NMR (CDCl₃) δ of 1.12 (t, J=7.0 Hz, 3H), 3.43 points (sq, J=7,0 Hz, 2H, in), 3.75 (t, J=5.0 Hz, 2H), to 4.38 (t, J=5.0 Hz, 2H), 4,88 (s, 2H), 7,45 (d, J=8,8 Hz, 1H), 7,53 (d, J=5,9 Hz, 1H).

Reference example 35:

The target product was obtained in the same manner as in Reference example 5, from compound obtained in Reference example 34.

¹H-NMR (CDCl₃) δ of 1.07 (t, J=7.0 Hz, 3H), 3,40 (sq, J=7,0 Hz, 2H), 3,76 (t, J=5.0 Hz, 2H), 4,73 (t, J=5.0 Hz, 2H), 7,63 d, J=8.5 Hz, 1H), 7,87 (d, J=6,1 Hz, 1H), to 10.09 (s, 1H).

Reference example 36:

The target product was obtained in the same manner as in Reference example 11, from the compound obtained in Reference example 35.

¹H-NMR (CDCl₃) δ of 1.06 (t, J=7.0 Hz, 3H), 3,40 (sq, J=7,0 Hz, 2H), 3,78 (t, J=5,1 Hz, 2H), 4,78 (t, J=5,1 Hz, 2H), 7,15-7,27 (m, 2H), 7,54-7,66 (m, 4H), 10,11 (s, 1H).

Example 109:N²-{[1-(2-ethoxyethyl)-5-fluoro-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 2 from the compound obtained in Reference example 36, and hydrochloride (L)-alaninemia.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.40 (d, J=7,0 Hz, 3H), 3,31-to 3.41 (m, 3H), and 3.72 (t, J=5.0 Hz, 2H), Android 4.04 (d, J=14,8 Hz, 1H), 4,12 (d, J=14,8 Hz, 1H), 4.26 deaths-of 4.38 (m, 2H), of 5.82 (users, 1H), 7,11-to 7.15 (m, 2H), 7,22 (users, 1H), 7,27 (d, J=6,6 Hz, 1H), 7,47 (d, J=10,7 Hz, 1H), 7,49-7,53 (m, 2H).

Reference example 37:

The target product was obtained in the same manner as in Reference examples 9 to 11, from 4-bromo-2-peritrabecular, ethylamine and 4-ftorhinolonovy acid.

¹H-NMR (CDCl₃) δ for 1.49 (t, J=7.2 Hz, 3H), 4,71 (sq, J=7.2 Hz, 2H), 7,18 (t, J=8.5 Hz, 2H), 7,58-to 7.64 (m, 4H), 7,98 (d, J=9,3 Hz, 1H), 10,12 (s, 1H).

Example 110:N²-{[1-ethyl-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 2, from the compound obtained in Reference example 37, and hydrochloride (L)-alaninemia.

¹H-NMR (CDCl₃) δ of 1.42 to 1.48 (m, 6H), 3,32 (sq, J=7,0 Hz, 1H), a 4.03 (d, J=14,8 Hz, 1H), 4,11 (d, J=14,8 Hz, 1H), 4,24 (sq, J=7,0 Hz, 2H), ceiling of 5.60 (users, 1H), 7,12-to 7.18 (m, 3H), 7,43-7,46 (m, 2H), EUR 7.57 to 7.62 (m, 2H), to 7.77 (m, 1H).

Reference example 38:

The target product was obtained in the same manner as in Reference example 37, 4-bromo-2,5-deformirovannoe.

¹H-NMR (CDCl₃) δ to 1.48 (t, J=7.2 Hz, 3H), 4,68 (sq, J=7.2 Hz, 2H), 7,14-7,20 (m, 2H), 7,46 (d, J=6,6 Hz, 1H), 7,53-to 7.59 (m, 2H), to 7.67 (d, J=10.5 Hz, 1H), 10,11 (s, 1H).

Example 111:N²-{[1-ethyl-5-fluoro-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 2 from the compound obtained in Reference example 38, and the hydrochloride of (L)-alaninemia.

¹H-NMR (CDCl₃) δ 1,42 of 1.46 (m, 6H), 3,31 (sq, J=7,0 Hz, 1H), 4,01 (d, J=14.6 Hz, 1H), 4,08 (d, J=14.6 Hz, 1H), 4,20 (sq, J=7,0 Hz, 2H), 5,41 (users, 1H),? 7.04 baby mortality (users, 1H), 7,13-to 7.18 (m, 2H), 7,28 (d, J=6,6 Hz, 1H), 7,49 (d, J=of 11.0 Hz, 1H), 7,52-of 7.55 (m, 2H).

Reference example 39:

To a solution of 2-chloro-6-foronline (2.5 g, and 17.2 mmol) in chloroform (40 ml) was added bromine (2,75 g, and 17.2 mmol) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into aqueous sodium thiosulfate solution and the mixture was extracted with chloroform. Org the organic layer was washed with water and saturated saline solution, was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (hexane:ethyl acetate=9:1-3:1) to obtain the target product (3,21 g, 83%).

¹H-NMR (CDCl₃) δ 7,07 (DD, J=10,0, 2.0 Hz, 1H), 7,19 (t, J=2.0 Hz, 1H).

Reference example 40:

The solution peroxoborate sodium tetrahydrate (11,0 g, to 71.5 mmol) in acetic acid (50 ml) was heated to 55°C was added dropwise a solution of compound (3,21 g, and 14.3 mmol)obtained in Reference example 39, in acetic acid (30 ml) for 1 hour. After stirring for 3 hours the mixture was allowed to cool to room temperature and the insoluble substance was filtered. The filtrate was poured into water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a column of silica gel (hexane:ethyl acetate=90:10 to 5:1) to obtain the target product (1,30 g, 36%).

¹H-NMR (CDCl₃) δ 7,39 (DD, J=8,3, 2.0 Hz, 1H), 7,50 (t, J=2.0 Hz, 1H).

Reference example 41:

The target product was obtained in the same manner as in Reference examples 9-11, from the compound obtained in Reference example 40, and 4-ftorhinolonovy acid.

¹H-NMR (CDCl₃) δ was 1.04 (t, J=7.0 Hz, 3H), 3,38(square, J=7,0 Hz, 2H), 3,79 (t, J=5,1 Hz, 2H), 4,79 (t, J=5,1 Hz, 2H), 7,12-to 7.18 (m, 2H), 7,51 to 7.62 (m, 4H), 10,12 (s, 1H).

Example 112:N²-{[4-chloro-1-(2-ethoxyethyl)-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 2 from the compound obtained in Referential example 41 and hydrochloride (L)-alaninemia.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.40 (d, J=7,0 Hz, 3H), 3,30-to 3.41 (m, 3H), 3,74 (t, J=5.0 Hz, 2H), 4,07 (d, J=14,8 Hz, 1H), 4,15 (d, J=14,8 Hz, 1H), 4,30-of 4.44 (m, 2H), 5,65 (users, 1H), 7,11-7,16 (m, 2H), 7,27 (users, 1H), 7,35 (d, J=1.4 Hz, 1H), 7,46 (d, J=1.4 Hz, 1H), 7,53-EUR 7.57 (m, 2H).

Reference example 42:

The target product was obtained in the same manner as in Reference example 40, 4-bromo-2-fluoro-5-methylaniline.

¹H-NMR (CDCl₃) δ 2,43 (s, 3H), of 7.48 (d, J=10.0 Hz, 1H), to 7.93 (d, J=7.8 Hz, 1H).

Reference example 43:

The target product was obtained in the same manner as in Reference example 41, from the compound obtained in Reference example 42.

¹H-NMR (CDCl₃) δ of 1.05 (t, J=7.0 Hz, 3H), of 2.34 (s, 3H), 3,40 (sq, J=7,0 Hz, 2H), of 3.77 (t, J=5.4 Hz, 2H), and 4.75 (t, J=5.4 Hz, 2H), 7,11-7,16 (m, 2H), 7,29-7,33 (m, 2H), 7,40 (s, 1H), of 7.70 (s, 1H), 10,10 (s, 1H).

Example 113:N²-{[1-(2-ethoxyethyl)-6-(4-forfinal)-5-methyl-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in PR is as 2, from the compound obtained in Reference example 43, and the hydrochloride of (L)-alaninemia.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.8 Hz, 3H), of 2.33 (s, 3H), 3,30-of 3.42 (m, 3H), 3,71 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,22-to 4.38 (m, 2H), 5,43 (users, 1H), 7,09-7,14 (m, 3H), 7,29-7,34 (m, 3H), to 7.61 (s, 1H).

Reference example 44:

The target product was obtained in the same manner as in Reference example 40, 4-bromo-2,6-diferencia.

¹H-NMR (CDCl₃) δ 7,28-to 7.32 (m, 2H).

Reference example 45:

The target product was obtained in the same manner as in Reference example 41, from the compound obtained in Reference example 44.

¹H-NMR (CDCl₃) δ of 1.06 (t, J=7.0 Hz, 3H), 3,41 (sq, J=7,0 Hz, 2H), 3,81 (t, J=5.3 Hz, 2H), to 4.81 (t, J=5.3 Hz, 2H), 7,15-7,19 (m, 2H), 7,27 (DD, J=11.0 in, and 1.6 Hz, 1H), 7,51 (d, J=1.6 Hz, 1H), EUR 7.57-to 7.61 (m, 2H), 10,16 (s, 1H).

Example 114:N²-{[1-(2-ethoxyethyl)-4-fluoro-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 2 from the compound obtained in Reference example 45, and hydrochloride (L)-alaninemia.

¹H-NMR (CDCl₃) δ is 1.11 (t, J=7.0 Hz, 3H), of 1.42 (d, J=6.8 Hz, 3H), 3,32 is-3.45 (m, 3H), of 3.77 (t, J=5.0 Hz, 2H), 4,08 (d, J=14.6 Hz, 1H), 4,18 (d, J=14.6 Hz, 1H), or 4.31-to 4.46 (m, 2H), 6,00 (users, 1H), 7,12-7,29 (m, 5H), 7,52-to 7.59 (m, 2H).

Reference example 46:

C is the left product was obtained in the same way, as in Reference example 40, 4-bromo-6-fluoro-3-triptorelin.

Reference example 47:

The target product was obtained in the same manner as in Reference example 41, from the compound obtained in Reference example 46.

¹H-NMR (CDCl₃) δ of 1.03 (t, J=7.0 Hz, 3H), 3,38 (sq, J=7,0 Hz, 2H), of 3.77 (t, J=5,1 Hz, 2H), 4,78 (t, J=5,1 Hz, 2H), 7,09-7,13 (m, 2H), 7,31-7,35 (m, 2H), 7,53 (s, 1H), 8,32 (s, 1H), 10,16 (s, 1H).

Example 115:N²-{[1-(2-ethoxyethyl)-6-(4-forfinal)-5-(trifluoromethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 2 from the compound obtained in Reference example 47, and hydrochloride (L)-alaninemia.

¹H-NMR (CDCl₃) δ of 1.09 (t, J=7.0 Hz, 3H), USD 1.43 (d, J=7,0 Hz, 3H), 3,31-of 3.42 (m, 3H), 3,71 (t, J=5.0 Hz, 2H), 4.09 to (d, J=to 15.0 Hz, 1H), 4,18 (d, J=to 15.0 Hz, 1H), 4,27-to 4.38 (m, 2H), 5,34 (users, 1H), 7,10 (t, J=8.7 Hz, 2H), 7,13 (users, 1H), 7,25 (s, 1H), 7,31 and 7.36 (m, 2H), 8,13 (s, 1H).

Reference example 48:

The target product was obtained in the same manner as in Reference examples 1, 3, 4 and 11, from 2.5-debtor-4-bromonitromethane, hydrochloride 4-aminotetrahydrofuran and 4-ftorhinolonovy acid.

¹H-NMR (CDCl₃) δ of 1.94 (m, 2H), 2,58 (m, 2H), 3,62 (m, 2H), 4,20 (m, 2H), 4,69 (m, 1H), 4.92 in (s, 2H), 7,12-7,21 (m, 2H), 7,45 (d, 1H, J=a 10.6 Hz), of 7.48-EUR 7.57 (m, 3H).

Reference example 49:

The solution is unity (0,82 g, of 2.38 mmol)obtained in Reference example 48, in dichloromethane (20 ml) was added diisopropylethylamine (2,12 ml of 11.9 mmol) and thionyl chloride (1 mol/l solution in dichloromethane, 11.9 ml, with 11.9 mmol). After heating at the boiling point under reflux for 1 hour the mixture was cooled to 0°C and to the mixture was added water. The mixture was neutralized with 2 mol/l aqueous solution of sodium hydroxide and was extracted with chloroform. The organic layer was washed with water and saturated saline solution, dried over sodium sulfate, concentrated under reduced pressure and the resulting residue is directly used for the next reaction.

¹H-NMR (CDCl₃) δ 1,96-2,05 (m, 2H), 2,55-2,70 (m, 2H), to 3.58-3,66 (m, 2H), 4,19-4,24 (m, 2H), br4.61 (m, 1H), 4,88 (s, 2H), 7,15-7,22 (m, 2H), 7,50-EUR 7.57 (m, 4H).

Example 116:N²-{[5-fluoro-6-(4-forfinal)-1-(tetrahydro-2H-Piran-4-yl)-1H-benzimidazole-2-yl]methyl}-L-alaninate

To a solution of compound (0.16 g, 0.44 mmol)obtained in Reference example 49, in tetrahydrofuran (5 ml) was added N-(2,4-dimethoxybenzyl)alaninate (0.12 g, 0.49 mmol), diisopropylethylamine (of 0.12 ml, 0.66 mmol) and sodium iodide (0.07 g, 0.44 mmol). After heating at the boiling point under reflux for 2 hours the mixture was allowed to cool to room temperature and added water. The mixture was extracted with chloroform and organically the layer was washed with saturated saline solution, was dried over sodium sulfate and concentrated under reduced pressure. To the residue was added triperoxonane acid (2 ml) and the mixture was heated to 50°C. After stirring for 1 hour the mixture was cooled to 0°C, was added chloroform and the mixture was neutralized with 2 mol/l aqueous solution of sodium hydroxide and was extracted with chloroform. The organic layer was washed with saturated saline solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified on a column of silica gel (chloroform:methanol=99:1-85:15) and recrystallized from ethyl acetate-hexane to obtain the target product (0.09 mg, 50%).

¹H-NMR (CDCl₃) δ of 1.40 (d, J=7,0 Hz, 3H), 1,86-1,89 (m, 2H), 2,49-of 2.64 (m, 2H), 3,32 (m, 1H), 3,53-3,61 (m, 2H), 4,11-4,20 (m, 4H), 4.53-in (m, 1H), 5,43 (users, 1H), 7,08 (users, 1H), 7,12-to 7.18 (m, 2H), 7,43-7,52 (m, 4H).

Reference example 50:

The target product was obtained in the same manner as in Reference examples 1-3, 2,4-deformirovannoe, 2-aminoethanol and 4-terfenol.

¹H-NMR (CDCl₃) δ of 3.23 (t, J=4,8 Hz, 2H), 3,84 (t, J=4,8 Hz, 2H), 6,28 (d, J=7.8 Hz, 1H), 6,37 (d, J=2.4 Hz, 1H), 6,66 (d, J=7.8 Hz, 1H), 6,27-6,98 (m, 4H).

Reference example 51:

To a solution of compound (2.7 g, 10.5 mmol)obtained in Reference example 50, N,N-dimethylformamide (50 ml) was added tert-butyl-diphenylsiloxane (3.6 ml, 126 mmol) and imidazole (1.1 g, 15.8 mmol) and the mixture was stirred at room temperature. After stirring for 1 hour to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure and the resulting residue is directly used for the next reaction.

¹H-NMR (CDCl₃) δ of 1.05 (s, 9H), and 3.16 (t, J=5,1 Hz, 2H), a 3.87 (t, J=5,1 Hz, 2H), 6,24-6,28 (m, 2H), 6,65 (d, J=8,1 Hz, 1H), 6,82-6,94 (m, 4H), 7,31-the 7.43 (m, 6H), 7,62-7,72 (m, 4H).

Reference example 52:

The target product was obtained in the same manner as in Reference examples 4 and 5 and Example 2 from the compound obtained in Reference example 51, and hydrochloride (L)-alaninemia.

¹H-NMR (CDCl₃) δ of 1.02 (s, 9H), of 1.45 (d, J=6.8 Hz, 3H), 3,34 (sq, J=6,8 Hz, 1H), 3,95 (t, J=5.4 Hz, 2H), 4.09 to (d, J=14,9 Hz, 1H), 4,14 (d, J=14,9 Hz, 1H), 4,23 is 4.36 (m, 2H), between 6.08 (users, 1H), 6.87 in-6,93 (m, 3H), 7,00-7,05 (m, 3H), 7,18 (users, 1H), 7,30 and 7.36 (m, 4H), 7,41-7,47 (m, 6H), 7,79 (d, J=8,8 Hz, 1H).

Example 117:N²-{[6-(4-pertenece)-1-(2-hydroxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate

To a solution (4 ml) of the compound (1.2 g, 2.0 mmol)obtained in Reference example 52, in THF was added tetrabutylammonium (1 mol/l solution in tetrahydrofuran, 3.0 ml, 3.0 mmol) and the mixture was stirred at room temperature. After stirring in the course is 1 hour to the mixture was added water and the mixture was extracted with chloroform. The organic layer was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified on a column of silica gel (chloroform:methanol=99:1-85:15) and recrystallized from chloroform-hexane to obtain the desired product (300 mg, 40%).

¹H-NMR (CDCl₃) δ of 1.32 (d, J=7,0 Hz, 3H), 3.33 and (sq, J=7,0 Hz, 1H), 3,92-3,98 (m, 2H), a 4.03 (d, J=13,6 Hz, 1H), 4,08 (d, J=13,6 Hz, 1H), 4,30 (t, J=4.6 Hz, 2H), 5,50 (users, 1H), 6,78 (users, 1H), 6,92-7,03 (m, 6H), to 7.64 (d, J=8,8 Hz, 1H).

Reference example 53:

To a solution of the compound (1.0 g, 4.4 mmol)obtained in Reference example 1 in N,N-dimethylformamide (44 ml) was added N-chlorosuccinimide (0.64 g, 4.8 mmol) and the mixture was heated to 40°C. After stirring over night the mixture was allowed to cool to room temperature. To the reaction mixture were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified on a column of silica gel (hexane:ethyl acetate=95:5-90:10-75:25 to 50:50) to obtain the target product (0,82 g, 72%).

¹H-NMR (CDCl₃) δ 1,22 (t, J=7.0 Hz, 3H), 3,41 (sq, J=5,2 Hz, 2H), 3,55 (sq, J=7,0 Hz, 2H), 3,69 (t, J=5,2 Hz, 2H), 6,62 (d, J=11.5 Hz, 1H), 8,27 (d, J=7.8 Hz, 1H), 8,31 (users, 1H).

Reference example 54:

The target product was obtained in the same manner as in Reference examples 2 to 5, from the compound obtained in Reference example 53.

¹H-NMR (CDCl₃) δ of 0.95 (t, J=7.0 Hz, 3H), 3,29 (sq, J=7,0 Hz, 2H), to 3.67 (t, J=5.0 Hz, 2H), 4,59 (t, J=5.0 Hz, 2H), of 6.96-7,10 (m, 5H), 7,98 (s, 1H), 10,02 (s, 1H).

Example 118:N²-{[5-chloro-1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate

The target product was obtained in the same manner as in Example 2 from the compound obtained in Reference example 54, and hydrochloride (L)-alaninemia.

¹H-NMR (CDCl₃) δ of 1.05 (t, J=7.0 Hz, 3H), of 1.40 (d, J=6.8 Hz, 3H), 3,29-to 3.38 (m, 3H), 3,63 (t, J=5.0 Hz, 2H), 4,01 (d, J=14,8 Hz, 1H), 4,10 (d, J=14,8 Hz, 1H), 4,15-to 4.28 (m, 2H), 5,68 (users, 1H), 6.87 in-6,91 (m, 2H), 6,97-7,02 (m, 3H), 7,16 (users, 1H), 7,80 (s, 1H).

Examples 119-190:

Connection Examples 119-190 presented in Tables 17-31, were obtained in accordance with methods described in the above Reference examples and Examples, or similar methods.

Table 17-1
Example	The structural formula	1H-NMR (CDCl3) δ
119		of 1.40 (d, J=7,0 Hz, 3H), of 1.55 (m, 1H), 1,80-of 1.95 (m,2H), 2,03 (m, 1H), 2,33 (s, 3H), 3,32 (sq, J=7,0 Hz, 1H), 3,70 (m, 1H), 3,80 (m, 1H), 4,01-is 4.21 (m, 5H), 5,57 (users, 1H), 6.87 in-7,01 (m, 4H), 7,12 (d, J=8,3 Hz, 2H), 7,27 (users, 1H), 7,65 (d, J=8,3 Hz, 1H).
120		of 1.41 (d, J=7,0 Hz, 3H), 1.57 in (m, 1H), 1,84-of 1.95 (m, 2H), 2.05 is (m, 1H), 3,32 (sq, J=7,0 Hz, 1H), 3,71 (m, 1H), 3,80 (m, 1H), a 4.03-4.25 in (m, 5H), 5,61 (users, 1H), 6,94-7,00 (m, 3H), 7,03 (d, J=2.4 Hz, 1H), 7,16 (d, J=8,4 Hz, 2H), 7.23 percent (users, 1H), 7,69 (d, J=8,4 Hz, 1H).

121		of 1.41 (d, J=7,0 Hz, 3H), 1.57 in (m, 1H), 1,80-2,10 (m, 3H), 3,31 (sq, J=7,0 Hz, 1H), 3,66-a-3.84 (m, 2H), 4,00-4,24 (m, 5H), 5.40 to (user., 1H), 6,78-7,05 (m, 5H), 7,24 (user., 1H), the 7.65 (d, J=8.6 Hz, 1H).
122		of 1.43 (d, J=7,0 Hz, 3H), 2,03 (m, 2H), 3,28-to 3.38 (m, 6H), was 4.02 (d, J=14,7 Hz, 1H), 4,08 (d, J=14,7 Hz, 1H), 4,21 (t, J=6,8 Hz, 2H), 5,47 (user., 1H), 6,66-6,84 (m, 2H), of 6.96 (DD, J=8,6, 2.2 Hz, 1H),? 7.04 baby mortality (d, J=2.2 Hz, 1H), 7,10 (m, 1H), 7,20 (user., 1H), 7,69 (d, J=8,8 Hz, 1H).

Table 17-2
123		of 1.42 (d, J=7,0 Hz, 3H), 2,02 (m, 2H), 3.25 to to 3.36 (m, 6H), 4.00 points (d, J=14,7 Hz, 1H), 4,06 (d, J=14,7 Hz, 1H), 4,19 (t, J=6,8 Hz, 2H), 5,55 (user., 1H), 6,79-7,06 (who, 5H), 7,21 (user., 1H), to 7.64 (d, J=8.6 Hz, 1H).

Table 18-1
Example	The structural formula	1H-NMR (CDCl3) δ
124		of 1.41 (d, J=6.8 Hz, 3H), of 1.55 (m, 1H), 1,75-2,10 (m, 3H), 3,35 (sq, J=6,8 Hz, 1H), 3,66-a-3.84 (m, 2H), 4,00-4,30 (m, 5H), of 5.45 (user., 1H), 6,70 (m, 1H), 6,80 (m, 1H), 6,95 (DD, J=8,6, 2.2 Hz, 1H), 7,01 (d, J=2.2 Hz, 1H), to 7.09 (m, 1H), 7,21 (user., 1H), 7,68 (d, J=8.6 Hz, 1H).
125		of 1.40 (d, J=7,0 Hz, 3H), of 1.55 (m, 1H), 1,80-2,10 (m, 3H), 3,34 (sq, J=7,0 Hz, 1H), 3,66-a 3.83 (m, 2H), 3,98-to 4.28 (m, 5H), 5,44 (user., 1H), 6,79-7,05 (m, 5H), 7,22 (user., 1H), to 7.64 (d, J=8.6 Hz, 1H).
126		of 1.42 (d, J=7,0 Hz, 3H), a 2.01 (m, 2H), 2,33 (s, 3H), of 3.28 (s, 3H), of 3.28 (m, 2H), 3.33 and (sq, J=7,0 Hz, 1H), 4.00 points (d, J=14,7 Hz, 1H), 4,07 (d, J=14,7 Hz, 1H), 4,18 (t, J=6,8 Hz, 2H), 5,50 (user., 1H), 6.87 in-7,02 (m, 4H), 7,12 (m, 2H), 7.23 percent (OSiR., 1H), to 7.64 (d, J=8.6 Hz, 1H).

127

of 1.42 (d, J=6.8 Hz, 3H), 2,03 (m, 2H), or 3.28 (s, 3H), 3,28-to 3.38 (m, 3H), was 4.02 (d, J=14,8 Hz, 1H) 4,08 (d, J=14,8 Hz, 1H), 4,21 (t, J=6.9 Hz, 2H), 5.56mm (user., 1H), 6,95-7,00 (m, 3H), 7,05 (d, J=2.2 Hz, 1H), 7,14-7,25 (m, 3H), of 7.69 (d, J=8,8 Hz, 1H).

Table 18-2
128		of 1.40 (d, J=7,0 Hz, 3H), 1,80-of 1.95 (m, 2H), 2,50 (m, 2H), 3,28 (sq, J=7,0 Hz, 1H), of 3.56 (m, 2H), 4,00-4,22 (m, 4H), 4,50 (m, 1H), 5,59 (user., 1H), 6,65-6,83 (m, 2H), 6.90 to (user., 1H), 6,95 (DD, J=8,8, 2.2 Hz, 1H), 7,10 (m, 1H), 7,28 (d, J=2.2 Hz, 1H), 7,69 (d, J=8,8 Hz, 1H).

Table 19-1
Example	The structural formula	1H-NMR (CDCl3) δ
129		of 1.40 (d, J=6.9 Hz, 3H), 1,78 is 1.86 (m, 2H), 2,33 (s, 3H), 2,43-of 2.58 (m, 2H), 3,28 (sq, J=6,9 Hz, 1H), 3,50-3,59 (m, 2H), 4,00-4,19 (m, 4H), 4,47 (m, 1H), 5,72 (users, 1H), 6.87 in-7,00 (m, 4H), 7,10-7,14 (m, 2H), 7,27 (d, J=2.2 Hz, 1H), 7,65 (d, J=8,8 Hz, 1H).
130		of 1.40 (d, J=6.9 Hz, 3H), 1,80 is 1.91 (m, 2H), 2,44 at 2.59 (m, 2H), 3,29 (sq, J=6,9 Hz, 1H), 3,50-3,60 (m, 2H), 4,01-is 4.21 (m, 4H), 4,50 (m, 1H), 5,86 (users, 1H), 6,92-7,00 (m, 4H), 7,14-7,20 (m, 2H), 7,31 (d, J=2.0 Hz, 1H), 7,69 (d, J=8,8 Hz, 1H).
131		of 1.40 (d, J=6.9 Hz, 3H), of 1.55 (m, 1H), 1,78-1,89 (m, 2H), 2,01 (m, 1H), 2,33 (s, 3H), 3,34 (sq, J=6,9 Hz, 1H), 3,71 (m, 1H), 3,79 (m, 1H), 3,98-4,27 (m, 5H), 5,57 (users, 1H), 6,86-6,91 (m, 2H), 6,93-7,01 (m, 2H,), 7,12 (d, J=8,3 Hz, 2H), 7,27 (users, 1H), 7,65 (d, J=8,3 Hz, 1H).
132		of 1.41 (d, J=6.9 Hz, 3H), and 1.56 (m, 1H), 1,79-of 1.95 (m, 2H), 2.05 is (m, 1H), 3,35 (sq, J=6,9 Hz, 1H), 3,70 (m, 1H), 3,80 (m, 1H), 3,99-is 4.21 (m, 4H), 4,25 (DD, J=14,8, 2.8 Hz, 1H), 5,68 (users, 1H), 6,94-7,00 (m, 3H), 7,03 (d, J=2.2 Hz, 1H), 7,13-7,19 (m, 2H), 7,22 (users, 1H), 7,69 (d, J=8.5 Hz, 1H).

Table 19-2
133		to 1.38 (d, J=6.8 Hz, 3H), 2,03-of 2.09 (m, 2H), 3,36-3,55 (m, 3H), 4,06 (d, J=14,3 Hz, 1H), 4,13 (d, J=14,3 Hz, 1H), 4,22-to 4.41 (m, 2H), 5,72 (users, 1H), 6,95-to 7.18 (m, 7H), to 7.68 (d, J=8.6 Hz, 1H).

Table 20
Example	The structural formula	1H-NMR (CDCl3) δ
134		of 1.32 (d, J=7,0 Hz, 3H), 3,35 (sq, J=7,0 Hz, 1H), 3.96 points (t, J=4,8 Hz, 2H), Android 4.04 (d, J=14,0 Hz, 1H), 4,10 (d, J=14,0 Hz, 1H), 4,32(t, J=4,8 Hz, 2H), 5,65 (users, 1H), 6,85 (users, 1H), 6,95-7,00 (m, 4H), 7,15-to 7.18 (m, 2H), 7,65 (d, J=9.4 Hz, 1H).
135		to 1.38 (t, J=7.2 Hz, 3H), of 1.47 (s, 6H), was 2.34 (s, 3H), of 3.97 (s, 2H), 4,10 (sq, J=7.2 Hz, 2H), 5,45 (user., 1H), 6,85-7,00 (m, 4H), 7,13 (m, 2H), 7,32 (user., 1H), the 7.65 (d, J=8,8 Hz, 1H).
136		1,00 of 1.28 (m, 4H), to 1.48 (s, 6H), 3,18 (m, 1H), 4,08 (s, 2H), 5,58 (user., 1H), 6.90 to-7,05 (m, 5H), to 7.15 (d, J=2.4 Hz, 1H), 7,42 (user., 1H), to 7.64 (d, J=8,8 Hz, 1H).
137		of 1.46 (s, 6H), 1.57 in (m, 1H), 1,80-2,10 (m, 3H), 3,67-a-3.84 (m, 2H), 3.96 points-of 4.25 (m, 5H), 5,33 (user., 1H), PC 6.82 (m, 1H), 6.89 in? 7.04 baby mortality (m, 4H), 7,45 (user., 1H), the 7.65 (d, J=8.6 Hz, 1H).

138

of 1.31 (t, J=7,3 Hz, 3H), of 1.47 (s, 6H), of 3.97 (s, 2H), 4,11 (sq, J=7,3 Hz, 2H), 5,59 (user., 1H), 6,92-7,06 (m, 6H), 7,30 (user., 1H), to 7.67 (m, 1H).

Table 21
Example	The structural formula	1H-NMR (CDCl3) δ
139		of 1.39 (t, J=7,1 Hz, 3H), of 1.42 (d, J=6.8 Hz, 3H), 3,32 (sq, J=6,8 Hz, 1H), 3,39 (d, J=14,8 Hz, 1H), 4,06 (d, J=14,8 Hz, 1H), 4,12 (m, 2H), 5,50 (user., 1H), 6,92-7,14 (m, 7H), to 7.67 (m, 1H).
140		of 1.47 (s, 6H), 1,78 is 1.86 (m, 2H), 2,33 (s, 3H), 2,44-of 2.58 (m, 2H), 3,48-to 3.58 (m, 2H), 4.00 points (s, 2H), 4,12-4,20 (m, 2H), to 4.41 (m, 1H), 5,65 (users, 1H), 6,86-6,91 (m, 2H), 6,94 (DD, J=8,8, 2.2 Hz, 1H), 7,10-7,14 (m, 2H), 7,17 (users, 1H), 7,26 (d, J=2.2 Hz, 1H), 7,65 (d, J=8,8 Hz, 1H).
141		of 1.09 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), 3,39 (sq, J=7,0 Hz, 2H), 3,70 (t, J=5.0 Hz, 2H), a 4.03 (s, 2H), 4.26 deaths (t, J=5.0 Hz, 2H), 5,41 (user., 1H), 6,70 (m, 1H), 6,80 (m, 1H), 6,94-to 7.15 (m, 3H), 7,46 (user., 1H), of 7.70 (d, J=8,4 Hz, 1H).
142		of 1.47 (s, 6H), 2,02 (m, 2H), 2,33 (s, 3H), of 3.28 (s, 3H), of 3.28 (m, 2H), 3,98 (s, 2H), 4,18 (t, J=6.9 Hz, 2H), 5,48 (user., 1H), 6.87 in-7,02 (m, 4H), 7,10 (d, J=8,2 Hz, 2H), 7,44 (user., 1H), the 7.65 (d, J=8.6 Hz, 1H).
143		1,45 (s, 6H), of 3.96 (t, J=4,8 Hz, 2H), 4,01 (s, 2H), 4,30 (t, J=4,8 Hz, 2H), 5,39 (users, 1H), 6,92-7,05 (m, 7H), the 7.65 (d, J=8.6 Hz, 1H).

Table 22-1
Example	The structural formula	1H-NMR (CDCl3) δ
144		of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.8 Hz, 3H), of 2.38 (s, 3H), 3.33 and-of 3.43 (m, 3H), 3,74 (t, J=5,1 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,15 (d, J=14,8 Hz, 1H), or 4.31-4,43 (m, 2H), of 5.89 (users, 1H), 7,26-to 7.32 (m, 4H), of 7.48-of 7.55 (m, 3H), 7,76 (d, J=8,3 Hz, 1H).
145		of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,32-of 3.42 (m, 3H), 3,76 (t, J=5,1 Hz, 2H), 4,07 (d, J=14,8 Hz, 1H), 4,15 (d, J=14,8 Hz, 1H), 4,30-to 4.41 (m, 2H), 5,75 (users, 1H), 7,25-to 7.32 (m, 3H), 7,45-7,47 (m, 2H), 7,63-the 7.65 (m, 2H), 7,78 (d, J=9.0 Hz, 1H).
146		of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.8 Hz, 3H), 3,32-of 3.42 (m, 3H), 3,76 (t, J=5.0 Hz, 2H), 4,07 (d, J=14.6 Hz, 1H), 4.16 the (d, J=14.6 Hz, 1H), or 4.31-4,43 (m, 2H), 5,70 (users, 1H), 7,25 (users, 1H), 7,49-7,52 (m, 2H), 7.68 per-7,74 (m, 4H), 7,80 (d, J=8,3 Hz, 1H).
147		of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,31-of 3.43 (m, 3H), of 3.75 (t, J=5.0 Hz, 2H), 4,08 (d, J=14,7 Hz, 1H), 4,17 (d, J=14,7 Hz, 1H), 4,30-4,43 (m, 2H), 5,73 (users, 1H), 6.90 to-7,00 (m, 2H), 7,28-to 7.50 (m, 4H), 7,79 (d, J=8,4 Hz, 1H).

Table 22-2
148		of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,34-of 3.43 (m, 3H), 3,76 (t, J=5.0 Hz, 2H), 4,08 (d, J=14,8 Hz, 1H), 4,15 (d, J=14,8 Hz, 1H), 4,29-4,43 (m, 2H), 5,98 (users, 1H), 7.18 in-7,44 (m, 6H), to 7.77 (d, J=and 8.4 Hz, 1H).

Table 23-1
Example	The structural formula	1H-NMR (CDCl3) δ
149		a 1.11 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), 3,40 (sq, J=7,0 Hz, 2H), of 3.77 (t, J=5.0 Hz, 2H), 4,06 (s, 2H), 4,36 (t, J=5.0 Hz, 2H), 5,47 (users, 1H), 7,12-7,17 (m, 2H), 7,44-7,46 (m, 2H), 7,51 (users, 1H), EUR 7.57-of 7.60 (m, 2H), 7,78 (m, 1H).

150		a 1.01 (t, J=7.4 Hz, 3H), 1,10 (t, J=7.0 Hz, 3H), 1,69-to 1.87 (m, 2H), and 3.16 (t, J=6.3 Hz, 1H), 3,39 (sq, J=7,0 Hz, 2H), 3,76 (t, J=5.0 Hz, 2H), Android 4.04 (d, J=14.6 Hz, 1H), 4.16 the (d, J=14.6 Hz, 1H), 4,30-4,45 (m, 2H,), 5,96 (users, 1H), 7,11-7,16 (m, 2H), 7,21 (users, 1H), 7,43-7,46 (m, 2H), 7,56-of 7.60 (m, 2H), to 7.77 (m, 1H).
151		to 1.00 (d, J=7,0 Hz, 3H), of 1.02 (d, J=7,0 Hz, 3H), 1,10 (t, J=7.0 Hz, 3H), of 2.08 (m, 1H), 2,98 (d, J=5.6 Hz, 1H), 3,40 (sq, J=7,0 Hz, 2H), 3,76 (sq, J=5,2 Hz, 2H), was 4.02 (d, J=14.4 Hz, 1H), 4,18 (d, J=14,4 Hz, 1H), ,31-4,49 (m, 2H), 5,66 (users, 1H), 7,09 (users, 1H), 7,12-7,17 (m, 2H), 7,44-7,46 (m, 2H), EUR 7.57-of 7.60 (m, 2H), 7,76 (m, 1H).

152

of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.8 Hz, 3H), of 2.45 (s, 3H), 3,32-of 3.42 (m, 3H), 3,76 (t, J=5,1 Hz, 2H), 4,06 (d, J=14,8 Hz, 1H), 4,15 (d, J=14,8 Hz, 1H), 4,30 was 4.42 (m, 2H), 5,68 (users, 1H), 7,16-7,52 (m, 7H), to 7.77 (m, 1H).

Table 23-2
153		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), to 2.29 (s, 3H), 3.33 and-of 3.42 (m, 3H), of 3.73 (t, J=5,1 Hz, 2H), 4,08 (d, J=14,8 Hz, 1H), 4.16 the (d, J=14,8 Hz, 1H), 4.26 deaths-of 4.38 (m, 2H), 5,66 (users, 1H), 7,22-7,30 (m, 7H), to 7.75 (m, 1H).

Table 24
Example	The structural formula	1H-NMR (CDCl3) δ
154		of 1.45 (t, J=7.0 Hz, 3H), of 1.48 (s, 6H), to 4.01 (s, 2H), 4,22 (sq, J=7,0 Hz, 2H), of 5.82 (users, 1H), 7,11-7,17 (m, 2H), 7,34 (users, 1H), 7,42 was 7.45 (m, 2H), 7,56-to 7.61 (m, 2H), to 7.77 (m, 1H).
155		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=6.8 Hz, 3H), 3,32-of 3.42 (m, 3H), 3,74 (t, J=5,1 Hz, 2H), 4,08 (d, J=14.6 Hz, 1H), 4.16 the (d, J=14.6 Hz, 1H), 4,29-to 4.41 (m, 2H), 5,41 (users, 1H), 7,06 (m, 1H), 7.24 to 7,30 (m, 3H), 7,35-7,39 (m, 2H), to 7.77 (d, J=8,3 Hz, 1H).
156		of 1.10 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), 3,40 (sq, J=7,0 Hz, 2H, in), 3.75 (t, J=5,1 Hz, 2H), 4,07 (s, 2H), 4,34 (t, J=5,1 Hz, 2H), lower than the 5.37 (users, 1H), 7,06 (m, 1H), 7.24 to 7,39 (m, 5H), to 7.77 (d, J=8,3 Hz, 1H).
157		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), and 2.27 (s, 3H), 3.33 and-of 3.42 (m, 3H), of 3.73 (t, J=5.4 Hz, 2H), 4,08 (d, J=to 15.4 Hz, 1H), 4,15 (d, J=to 15.4 Hz, 1H), 4,27-and 4.40 (m, 2H), 5,35 (users, 1H), 6,92-7,01 (m, 2H), 7,17-7,25 (m, 3H), 7,29 (users, 1H), 7,34 (d, J=8,3 Hz, 1H).

158

a 1.11 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), and 2.26 (s, 3H), 3,40 (sq, J=7,0 Hz, 2H), 3,74 (t, J=5.0 Hz, 2H), 4,07 (s, 2H), 4,33 (t, J=5.0 Hz, 2H), 5,47 (users, 1H), 6,92-7,01 (m, 2H), 7,17-7,27 (m, 3H), 7,54 (users, 1H), of 7.75 (d, J=8,3 Hz, 1H).

Table 25-1
Example	The structural formula	1H-NMR (CDCl3) δ
159		of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), and 2.26 (s, 3H), of 2.38 (s, 3H), 3,32-of 3.42 (m, 3H), and 3.72 (t, J=5,1 Hz, 2H), 4,07 (d, J=14.6 Hz, 1H), 4,15 (d, J=14.6 Hz, 1H), 4.26 deaths-of 4.38 (m, 2H), 5,81 (users, 1H), 7,07-7,27 (m, 5H), 7,33 (users, 1H), 7,73 (d, J=8,3 Hz, 1H).
160		of 1.10 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), and 2.26 (s, 3H), of 2.38 (s, 3H), 3,39 (sq, J=7,0 Hz, 2H), of 3.73 (t, J=5,1 Hz, 2H), 4,06 (s, 2H), 4,32 (t, J=5,1 Hz, 2H), 5,49 (users, 1H), 7,06-7,26 (m, 5H), 7,55 (users, 1H), 7,75 (d, J=8,3 Hz, 1H).
161		a 1.11 (t, J=7.0 Hz, 3H), of 1.42 (d, J=6.8 Hz, 3H), 2,32 (s, 3H), of 2.36 (s, 3H), 3,31-of 3.43 (m, 3H), 3,76 (t, J=5.0 Hz, 2H), 4,07 (d, J=14,9 Hz, 1H), 4.16 the (d, J=14,9 Hz, 1H), 4,29-of 4.44 (m, 2H), are 5.36 (users, 1H), 7.23 percent (m, 1H), was 7.36 (users, 1H), 7,30-7,51 (m, 4H), 7,76 (d, J=9.0 Hz, 1H).
162		of 1.10 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), 2,32 (s, 3H), of 2.36 (s, 3H), 3,39 (sq, J=7,0 Hz, 2H), of 3.77 (t, J=5.0 Hz, 2H), 4,06 (s, 2H), 4,36 (t, J=5.0 Hz, 2H), 5,28 (users, 1H), 7,22 (m, 1H), 7,37-7,51 (m, 4H), 7,55 (users, 1H), to 7.77 (d, J=8.6 Hz, 1H).

Table 25-2
163		a 1.01 (t, J=7.5 Hz, 3H), 1,10 (t, J=7.0 Hz, 3H), 1,65-of 1.85 (m, 2H), 2,32 (s, 3H), of 2.36 (s, 3H), and 3.16 (t, J=6.3 Hz, 1H) 3,39 (square, J=7,0 Hz, 2H), 3,76 (t, J=5,2 Hz, 2H), 4,05 (d, J=14,7 Hz, 1H), 4.16 the (d, J=14,7 Hz, 1H), 4,29-to 4.46 (m, 2H), 5,42 (users, 1H), 7,22 (m, 2H), was 7.36-7,52 (m, 4H), 7,76 (d, J=9.0 Hz, 1H).

Table 26-1
Example	The structural formula	1H-NMR (CDCl3) δ
164		of 1.09 (t, J=7.0 Hz, 3H), USD 1.43 (d, J=7,1 Hz, 3H), a 2.01 (s, 6H), to 2.35 (s, 3H), 3.33 and-to 3.41 (m, 3H), 3,76 (t, J=5.0 Hz, 2H), 4,07 (d, J=14,8 Hz, 1H), 4,14 (d, J=14,8 Hz, 1H), 4,24 is 4.36 (m, 2H), lower than the 5.37 (users, 1H), 6,97 (s, 2H),? 7.04 baby mortality (DD, J=8.0 a, and 1.6 Hz, 1H), 7,10 (d, J=1.6 Hz, 1H), 7,32 (users, 1H), 7,76 (d, J=8.0 Hz, 1H).
165		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 2,41 (s, 3H), 3,31-of 3.43 (m, 3H), of 3.75 (t, J=5,1 Hz, 2H), 4,07 (d, J=14,7 Hz, 1H), 4.16 the (d, J=14,7 Hz, 1H), 4,28 was 4.42 (m, 2H), 5,33 (users, 1H), 6,98-7,06 (m, 2H), 7,27 (users, 1H), 7,35-7,49 (m, 3H), 7,78 (d, J=8,4 Hz, 1H).
166		of 1.10 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), is 2.41 (s, 3H), 3,39 (sq, J=7,0 Hz, 2H), 3,76 (t, J=5,1 Hz, 2H), 4,07 (s, 2H), 4,35 (t, J=5,1 Hz, 2H), 5,31 (users, 1H), of 6.96-7,05 (m, 2H), 7,35-7,49 (m, 3H), 7,52 (users, 1H), 7,78 (d, J=8,4 Hz, 1H).
167		a 1.11 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), of 2.36 (s, 3H), 3,31-3,44 (m, 3H), 3,76 (t, J=5,2 Hz, 2H), 4,07 (d, J=14,8 Hz, 1H), 4.16 the (d, J=14,8 Hz, 1H), 4,28-of 4.44 (m, 2H), lower than the 5.37 (users, 1H), was 7.08 (t, J=8,9 Hz, 1H), 7,37-7,46 (m, 5H), to 7.77 (d, J=9.0 Hz, 1H).

Table 26-2
168		a 1.11 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), a 2.36 (s, 3H), 3,40 (sq, J=7,0 Hz, 2H), of 3.77 (t, J=5.0 Hz, 2H), 4,06 (s, 2H), 4,36 (t, J=5.0 Hz, 2H), and 5.30 (users, 1H), was 7.08 (t, J=8,8 Hz, 1H), was 7.36-7,46 (m, 4H), 7,51 (users, 1H), to 7.77 (d, J=8,1 Hz, 1H).

Table 27-1
Example	The structural formula	1H-NMR (CDCl3) δ
169		a 1.11 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), of 2.33 (s, 3H), 3,31-3,44 (m, 3H), 3,76 (t, J=5.0 Hz, 2H), 4,07 (d, J=14,8 Hz, 1H), 4.16 the (d, J=14,8 Hz, 1H), 4,29-of 4.44 (m, 2H), 5,42 (users, 1H), 7.23 percent-7,33 (m, 4H), 7,42-7,49 (m, 2H), to 7.77 (d, J=8,8 Hz, 1H).
170		a 1.11 (t, J=7.0 Hz, 3H), of 1.47 (s, 6H), of 2.33 (s, 3H), 3,40 (sq, J=7,0 Hz, 2H), of 3.77 (t, J=5.0 Hz, 2H), 4,07 (s, 2H), 4,36 (t, J=5.0 Hz, 2H), 5,35 (users, 1H), 7,22-7,33 (m, 4H), 7,46 to 7.4 (m, 2H), 7,78 (d, J=9.0 Hz, 1H).
171		of 1.09 (t, J=7.0 Hz, 3H), of 1.42 (d, J=6.8 Hz, 3H), 3,34-of 3.42 (m, 3H), of 3.75 (t, J=5,1 Hz, 2H), 4.09 to (d, J=14,8 Hz, 1H), 4.16 the (d, J=14,8 Hz, 1H), 4,29-to 4.41 (m, 2H), 5,67 (users, 1H), 7,14-7,16 (m, 2H), 7.23 percent-7,30 (m, 2H), 7,41-7,52 (m, 2H), 7,80 (d, J=8.5 Hz, 1H).
172		of 1.10 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,31-of 3.42 (m, 3H), 3,74 (t, J=5,1 Hz, 2H), 3,81 (s, 3H), 4,07 (d, J=14,8 Hz, 1H), 4,15 (d, J=14,8 Hz, 1H), 4,28-and 4.40 (m, 2H), lower than the 5.37 (users, 1H), 6.73 x-is 6.78 (m, 2H), 7,28-7,41 (m, 4H), of 7.75 (d, J=8,3 Hz, 1H).

Table 27-2
173		a 1.11 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 3,32-of 3.43 (m, 3H), 3,76 (t, J=5.0 Hz, 2H), 3,98 (s, 3H), 4,08 (d, J=14,8 Hz, 1H), 4.16 the (d, J=14,8 Hz, 1H), or 4.31-4,43 (m, 2H), 5.40 to (users, 1H), 7,13-7,20 (m, 4H), 7,44-7,46 (m, 2H), 7,78 (d, J=9.0 Hz, 1H).

Table 28
Example	The structural formula	1H-NMR (CDCl3) δ
174		1,11 (who, J=7,0 Hz, 3H), of 1.47 (s, 6H), 3,39 (sq, J=7,0 Hz, 2H, in), 3.75 (t, J=5,1 Hz, 2H), 3,81 (s, 3H), 4,06 (s, 2H), 4,33 (t, J=5,1 Hz, 2H), are 5.36 (users, 1H), 6,72-of 6.78 (m, 2H), 7,28-7,40 (m, 3H), 7,53 (users, 1H), 7,75 (d, J=8,3 Hz, 1H).
175		a 1.11 (t, J=7.0 Hz, 3H), of 1.48 (s, 6H), 3,39 (sq, J=7,0 Hz, 2H), of 3.77 (t, J=5,1 Hz, 2H), 3,98 (s, 3H), 4,07 (s, 2H), 4,37 (t, J=5,1 Hz, 2H), from 5.29 (users, 1H), 7,14-7,20 (m, 4H), 7,44-7,51 (m, 2H), 7,78 (d, J=8.0 Hz, 1H).
176		of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (t, J=7.0 Hz, 3H), 3,32-of 3.42 (m, 3H), 3,71 (t, J=5,1 Hz, 2H), 4,05 (d, J=14.6 Hz, 1H), 4,14 (d, J=14.6 Hz, 1H), 4,23-to 4.38 (m, 2H), 5,39 (users, 1H), 7,11-7,17 (m, 3H), 7,21 (users, 1H), 7,41 was 7.45 (m, 2H), 7,83 (s, 1H).
177		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 3,31-of 3.43 (m, 3H), 3,71 (t, J=5.0 Hz, 2H), 4,07 (d, J=14,8 Hz, 1H), 4,17 (d, J=14,8 Hz, 1H), 4,24-4,39 (m, 2H), ceiling of 5.60 (users, 1H), 7.24 to 7,47 (m, 7H), to 7.84 (s, 1H).
178		of 1.10 (t, J=7.0 Hz, 3H), USD 1.43 (d, J=7,0 Hz, 3H), of 2.44 (s, 3H), 3,32-of 3.42 (m, 3H), 3,71 (t, J=5.0 Hz, 2H), 4,07 (d, J=14,8 Hz, 1H), 4,15 (d, J=14,8 Hz, 1H), 4,25-to 4.38 (m, 2H), 5,61 (users, 1H), 7,26-7,39 (m, 6H), 7,83 (s, 1H).

Table 29
Example		The structural formula	1H-NMR (CDCl3) δ
179		a 1.08 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,30-to 3.41 (m, 3H), 3,70 (t, J=5.0 Hz, 2H), 4,05 (d, J=15.1 Hz, 1H), 4,13 (d, J=15.1 Hz, 1H), 4,24 is 4.36 (m, 2H), 5,67 (users, 1H), 6.90 to-6,98 (m, 2H), 7,21 (users, 1H), 7,28-7,34 (m, 2H), to 7.84 (s, 1H).
180		of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,30-to 3.41 (m, 3H), 3,71 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,25-4,37 (m, 2H), 5,68 (users, 1H), 7,15-7,30 (m, 5H), 7,81 (s, 1H).
181		of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=7,0 Hz, 3H), 3,30-of 3.42 (m, 3H), 3,70 (t, J=5.0 Hz, 2H), 4,05 (d, J=to 15.0 Hz, 1H), 4,14 (d, J=to 15.0 Hz, 1H), 4,23-to 4.38 (m, 2H), 5,63 (users, 1H), 7,20 (users, 1H), 7,26-7,30 (m, 3H), 7,47-to 7.50 (m, 2H), 7,83 (s, 1H).
182		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 3,37-3,44 (m, 3H), and 3.72 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,14 (d, J=14,8 Hz, 1H), 4,25 is 4.35 (m, 2H), 7,31 (m, 1H), 7,56-to 7.59 (m, 2H), 7,70-7,73 (m, 2H), to 7.84 (s, 1H).

183

of 1.10 (t, J=7 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 3,31-of 3.43 (m, 3H), 3,74 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,14 (d, J=14,8 Hz, 1H), 4,28-and 4.40 (m, 2H), 5,54 (users, 1H), 7,18 (users, 1H), 7,21-7,29 (m, 3H), 7,39 (m, 1H), 7,49 (s, 1H).

Table 30-1
Example	The structural formula	1H-NMR (CDCl3) δ
184		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 2,42 (s, 3H), 3,31-of 3.42 (m, 3H), of 3.73 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4.26 deaths-of 4.38 (m, 2H), 5.56mm (users, 1H), 7,24 (users, 1H), 7,26-7,30 (m, 3H), 7,46 is 7.50 (m, 3H).
185		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), 3,31-of 3.42 (m, 3H), of 3.73 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,27-4,39 (m, 2H), 5,58 (users, 1H), 7.23 percent (users, 1H), 7,32 (d, J=6.3 Hz, 1H), 7,39 (m, 1H), 7,45-7,51 (m, 3H), EUR 7.57-to 7.59 (m, 2H).
186		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=6.8 Hz, 3H), 3,31-of 3.42 (m, 3H), of 3.73 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,27-4,39 (m, 2H), are 5.36 (users, 1H), 7,20 (users, 1H), 7,29 (d, J=6,6 Hz, 1H), 7,42-7,44 (m, 3H), of 7.48-7,52 (m, 2H).
187

Table 30-2
188		a 1.11 (t, J=7.0 Hz, 3H), of 1.42 (d, J=7,0 Hz, 3H), of 2.35 (s, 3H), 3,30-of 3.43 (m, 3H), of 3.73 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,14 (d, J=14,8 Hz, 1H), 4,27-4,39 (m, 2H), 5,35 (users, 1H), to 7.09 (t, J=8,8 Hz, 1H), 7.23 percent (users, 1H), 7,34-7,39 (m, 3H), of 7.48 (d, J=10,8 Hz, 1H).

Table 31
Example	The structural formula	1H-NMR (CDCl3) δ
189		of 1.10 (t, J=7.0 Hz, 3H), of 1.42 (d, J=6.8 Hz, 3H), of 2.34 (s, 3H), 3,31-of 3.42 (m, 3H), of 3.73 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,28-and 4.40 (m, 2H), 5,42 (users, 1H), 7,22-7,31 (m, 5H), 7,49 (d, J=10,7 Hz, 1H).
190		of 1.09 (t, J=7.0 Hz, 3H), of 1.41 (d, J=6.8 Hz, 3H), of 2.33 (s, 3H), 3,31-to 3.41 (m, 3H), 3,71 (t, J=5.0 Hz, 2H), 4,05 (d, J=14,8 Hz, 1H), 4,13 (d, J=14,8 Hz, 1H), 4,24 is 4.36 (m, 2H), 5,41 (users, 1H), 7,07-7,26 (m, 5H), 7,60 (s, 1H).

Reference example 55:

To a solution of compound (1.4 g, 5.0 mmol)obtained in the same manner as in Reference examples 9 and 10, from 2-fluoro-5-bromo-nitrobenzene, tetrahydrofuran (30 ml) was added anhydrous sodium sulfate (3.8 g, 26.8 mmol), triethylamine (2.1 ml, to 15.4 mmol) and hydrochloride (L)-alaninemia (1.9 grams, of 15.2 mmol) and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added cyanoborohydride sodium (0.33 g, 5.2 mmol) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with chloroform. The organic layer was washed with saturated saline solution, dried over sodium sulfate and concentrated. The residue was purified on a column of silica gel (dichloromethane:methanol=99:1-95:5) to obtain the target product (0,89 g, 51%).

Reference example 56:

To a solution of compound (0,48 g, 1.3 mmol)obtained in Reference example 55, in dichloroethane (10 ml) was added di-tert-butylboronic (1.4 g, 6.5 mmol) and diisopropylethylamine (0.33 ml, of 1.95 mmol) and the mixture was stirred at 80°C for 14 hours. To the reaction mixture were added dichloromethane and the mixture was washed with water and saturated salt solution. The organic layer was dried over sodium sulfate and concentrated. The balance of cleansing and on a column of silica gel (dichloromethane:methanol=99:1-97:3) to obtain the target product (500 mg, 82%).

Reference example 57:

To a solution (3:1, 4 ml) of the compound (50 mg, 0.11 mmol)obtained in Reference example 56, in an aqueous solution of acetonitrile was added 4-chlorophenylalanine acid (34 mg, 0.22 mmol), 3 mol/l aqueous sodium hydrogen carbonate solution (90 μl) and tetrakis(triphenylphosphine)palladium (13 mg, 0,00112 mmol) and the mixture was stirred at 85°C for 5 hours in an argon atmosphere. The reaction mixture was filtered through celite and the filtrate was concentrated. Added ethyl acetate and a saturated aqueous solution of sodium bicarbonate to separate the residue. The organic layer was washed with water, dried and concentrated. The residue was purified on a column of silica gel (ethyl acetate) to obtain the target product (48 mg, 90%).

Example 191:the hydrochloride of N²-{[5-(4-chlorophenyl)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninemia

Solution (3 ml) of the compound (48 mg, 0.10 mmol)obtained in Reference example 57, in hydrochloric acid-dioxane was stirred at room temperature for 1 hour. The reaction mixture was concentrated and the resulting powder was washed with diethyl ether to obtain the desired product (25 mg, 76%).

Example 192:triptorelin N²-{[1-(2-ethoxyethyl)-5-(4-methoxyphenyl)-1H-benzimidazole-2-yl]methyl}-L-alaninemia

To a solution (3 ml) of the compound (62 mg, 0.13 mmol)obtained in the above Reference example, in dichloromethane was added triperoxonane acid (0.3 ml) under ice cooling. The mixture was allowed to warm to room temperature and was stirred for 1 hour. The reaction mixture was concentrated and was led from diethyl ether to obtain the desired product (48 mg, 76%).

Example 193-208:

Compounds shown in Table 32 were obtained in accordance with methods described in the above Reference examples and Examples, or similar methods.

Compounds were identified in accordance with the LC/MS spectrum and retention time of any of the following methods.

conditions 1 analysis

detector: LCMS/MS API2000 (manufactured by Applied Biosystems)

column: Phenomenex Gemini C18 of 4.6×50 mm, 5 µm

the wavelength of detection: 220 nm, 260 nm

flow rate: 1.2 ml/min

the composition of the solvent for elution: SOLUTION A: of 0.05% aqueous TFA, of 0.05% aqueous HCOOH or 10 mm aqueous ammonium acetate SOLUTION B: acetonitrile

gradient: 0-0,01 B 10%, from 0.01 to 1.50 min B 10% to 30%, 1,50-3,00 min B 30% to 90%, 3,00-4,00 min B 90%, 4,00-5,00 min B 90% to 10%

conditions 2 analysis

detector: LCMS/MS API2000 (manufactured by Applied Biosystems)

column: Phenomenex Gemini C18 of 4.6×50 mm, 5 µm

the wavelength of detection: 220 nm, 260 nm

flow rate: 1 ml/min/p>

the composition of the solvent for elution: SOLUTION A: of 0.05% aqueous TFA, of 0.05% aqueous HCOOH or 10 mm aqueous ammonium acetate SOLUTION B: acetonitrile

gradient: 0-0,01 B 5%, 0,01-1,00 min B 5%, and 1.00-7,00 minutes B 5% to 50%7,00-10,00 min B 50% to 90%10,00-11,00 minutes B 90%, 11,00-12,00 minutes B 90% to 5%

Table 32-1

Table 32-2

Reference example 58:

To a solution (25 ml) of iron (3.7 g, 66 mmol) and ammonium chloride (1.04 g, 19 mmol) in mixed solvent (3:2:1) tetrahydrofuran-methanol-water was added dropwise a solution (25 ml) of the compound (1.7 g, 6,9 mmol)obtained in Reference example 18, in a mixed solvent (3:2:1) tetrahydrofuran-methanol-water at 70°C. After 1.5 hours the mixture was allowed to cool to room temperature and the reaction mixture was filtered through celite. The filtrate was concentrated, added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated with the teachings of the target product (1,32 g, 89%). The product was used for next reaction without purification.

Reference example 59:

The target product was obtained in the same manner as in Reference examples 4, 5, 55 and 56.

Reference example 60:

To a solution of compound (60 mg, 0.14 mmol)obtained in Reference example 59, and 4-methylphenylacetic acid (38 mg, 0.28 mmol) in n-butanol (2 ml) was added potassium phosphate (60 mg, 0.28 mmol), palladium acetate (3.2 mg, 0.014 mmol) and S-phos (11.6 mg, 0,0038 mmol) and the mixture was stirred at 100°C for 14 hours in an argon atmosphere. After cooling, the reaction mixture was filtered through celite and washed with methanol. The filtrate was concentrated, to the mixture was added ethyl acetate and the mixture washed with saturated aqueous sodium hydrogen carbonate solution and saturated saline solution, dried and concentrated. The residue was purified on a column of silica gel (ethyl acetate:hexane=65:35) to obtain the target product (43 mg, 52%).

Example 209:the hydrochloride of N²-{[3-(2-ethoxyethyl)-5-(4-were)-3H-imidazo[4,5-b]pyridine-2-yl]methyl}-L-alaninemia

To a solution of compound (34 mg)obtained in Reference example 60, in dioxane (1 ml) solution was added 4 mol/l hydrochloric acid-dioxane (2 ml) under cooling with ice. The mixture was allowed to warm to room temperature and was stirred for 10 hours. The reaction mixture was concentrated and the resulting powder was washed with diethyl ether to obtain the desired product (28 mg, 95%).

Examples 210-226:

Compounds shown in Table 33 were obtained in accordance with methods described in the above Reference examples and Examples, or similar methods.

Compounds were identified in accordance with the LC/MS spectrum and retention time under conditions similar to those described above.

Table 33-1

Table 33-2

Table 33-3

Example 227-237:

Connection Examples 227-237, presented in Table 34 and Table 35 were obtained in the same manner as in Reference examples 18-20 and Example 79.

Compounds identified in accordance the with the LC/MS spectrum and retention time in the conditions, similar to that described above.

Table 34

Table 35

The compounds presented in Tables 36-38, can be obtained in accordance with methods described in the above Reference examples and Examples, or similar methods.

Table 36

Table 37

Table 38

Experimental Example 1

Experiment on inhibition of TTX-resistant Na channel for expressing human SNS gene cell

Expressing human SNS gene cell was obtained by inclusion of human SNS gene in the cell of the ovary of the Chinese hamster (CHO-K1) and gave stably expressed. Since CHO-K1 cell initially contains no such component, as the TTX-resistant Na channel component of the TTX-resistant Na channel expressing human SNS gene cells is SNS and the connection of the present invention is an inhibitor SNS.

1) design expressing human SNS gene cells and confirmation of expression of SNS functions

A full-sized human gene for the α subunit of the SNS included in expressing plasmid (pcDNA3,1Zeo(+)), containing the gene for resistance to Zeocin, and a full-length light chain gene Annexin II was introduced in expressing plasmid (pcDNA3,1 (+))containing the gene of resistance to Neomycin. These two genes were simultaneously introduced into CHO-K1 cell using lipofectamine 2000, were cultured in F-12 medium containing Neomycin and Zeocin, and chose the cell resistant to both drugs, namely the cell containing both genes. Strain resistant to two drugs were subjected to restrictive breeding twice and cloned including SNS gene of the cell. Transgenic SNS on what was tweedale using RT-PCR, TTX-resistant component that responds to the stimulation of Na channel was determined using sensitive to the membrane potential fluorescent indicator and confirmed the functional expression of SNS.

2) pharmacological effect on TTX-resistant Na channel expressing human SNS gene cells

Using expressing human SNS cells obtained as described above in 1, was evaluated SNS inhibitory effect of the compounds of the present invention. More specifically, the test compound was added in advance to expressing human SNS cage, after about 30 minutes was added veratridine (50 μm), a stimulator of the Na channel in the presence of TTX (1 μm), the membrane potential was increased through TTX-resistant Na channel and assessed the suppressive effect of the test compound to increase the membrane potential.

3) pharmacological evaluation

The degree of inhibition of the SNS test compound was determined using the following calculation formula.

The degree of inhibition of SNS (%)=100×[(the maximum value of the stimulation only veratridine without test compound)-(maximum value with stimulation veratridine with the test compound)]/[(maximum value during stimulation only veratridine without test compound)-(default value without stimulation]

4) test results

The compounds obtained in examples were evaluated for their effect on inhibition (Degree of inhibition SNS) TTX-resistant Na channel in expressing human SNS cage. As a result, it was found that the compound of the present invention demonstrates SNS inhibitory action. The degree of inhibition of SNS (%) at a concentration of compounds 12.5 μm are presented in Tables 39-47.

Industrial applicability

New bicyclic heterocyclic compound of the present invention can be used as an excellent drug for the treatment or prophylaxis of a pathology involving SNS, in particular diseases such as neuropathic pain, nociceptive pain, urination disorder, multiple sclerosis and the like.

1. The compound represented by the following formula (1):

where
R¹presented yet a
(1) a hydrogen atom,
(2) a halogen atom,
(3) C_1-6alkyl group, or
(4) C_1-6halogenating group
(where R¹may be present as a substituent of the benzene or pyridine ring at any substitutable position on the ring);
L is a
(1) a simple link,
(2) -O - or
(3) -CH₂O-
(where L may be present as a substituent in position 5 or 6 of the condensed cycle);
R²represents a
(1) C_6-10aryl group (C_6-10aryl group optionally is condensed with C_3-6cycloalkanes), optionally substituted by substituent(s)selected from:
(a) a halogen atom,
(b) C_1-6alkyl group,
(c) C_1-6halogenoalkanes group,
(d) C_1-6alkoxygroup,
(e) C_1-6halogenlampe and
(f) ceanography, or
(2) a 5-6-membered aromatic heterocyclic group containing a nitrogen atom or an oxygen atom,
X represents a carbon atom or a nitrogen atom,
R³represents a
(1) C_1-6alkyl group optionally substituted by substituent(s)selected from
(a) C_1-6alkoxygroup,
(b) a 5-6-membered saturated aliphatic heterocyclic group containing an oxygen atom, and
(c) a hydroxyl group,
(2) C_3-8cycloalkyl group or
(3) a 5-6-membered us is on aliphatic heterocyclic group, containing a nitrogen atom or an oxygen atom, optionally substituted by substituent(s)selected from
(a) C_1-6alkyl-carbonyl group,
(b) C_1-6alkoxy-carbonyl group,
(c) C_1-6alkylsulfonyl group and
(d) carbamoyl group, optionally mono - or disubstituted by C_1-6alkyl group (or groups),
R⁴represents a
(1) a hydrogen atom, or
(2) C_1-6alkyl group,
R^5aand R^5beach independently represent
(1) a hydrogen atom, or
(2) C_1-6alkyl group, or
R⁴and R^5anot necessarily related to education, together with the nitrogen atom is linked to R⁴, 5-6-membered saturated nitrogen-containing aliphatic heterocycle (in this case, R^5brepresents a hydrogen atom), and
R⁶and R⁷each independently represent
(1) a hydrogen atom, or
(2) C_1-6alkyl group optionally substituted by substituent(s)selected from
(a) a hydroxyl group,
(b) C_1-6alkoxygroup and
(c) a 5-6-membered saturated aliphatic heterocyclic group containing 1 or 2 heteroatoms selected from nitrogen atom and oxygen atom, or
R⁶and R⁷not necessarily related to education, together with the nitrogen atom to which they relate, 5-6-membered saturated aliphatic hetaeras the cycle, containing 1 or 2 heteroatoms selected from a nitrogen atom or oxygen atom, optionally substituted by substituent(s)selected from
(a) the carbonyl group,
(b) ceanography and
(c) C_1-6halogenoalkanes group;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, which is represented by the following formula (2):

where R¹, R², R³, R⁴, R^5a, R^5b, R⁶, R⁷, L and X have the meanings defined in claim 1, or its pharmaceutically acceptable salt.

3. The compound according to claim 1, where R²represents a phenyl group optionally substituted by substituent(s)selected from:
(a) a halogen atom,
(b) C_1-6alkyl group,
(c) C_1-6halogenoalkanes group,
(d) C_1-6alkoxygroup,
(e) C_1-6halogenlampe and
(f) ceanography,
or its pharmaceutically acceptable salt.

4. The compound according to claim 1, where X represents a carbon atom, or its pharmaceutically acceptable salt.

5. The compound according to claim 1, where R¹represents a hydrogen atom or halogen atom, or its pharmaceutically acceptable salt.

6. The compound according to claim 1, where L represents-O-, or its pharmaceutically acceptable salt.

7. The compound represented by the following formula (1):

where
R¹before the hat is
(1) a hydrogen atom, or
(2) a halogen atom
(where R¹may be present as a substituent of the benzene or pyridine ring at any substitutable position on the ring);
L is a
(1) a simple link or
(2) -O-
(where L may be present as a substituent in position 5 or 6 of the condensed cycle);
R²represents a phenyl group optionally substituted by substituent(s)selected from
(a) a halogen atom,
(b) C_1-6alkyl group,
(c) C_1-6halogenoalkanes group,
(d) C_1-6alkoxygroup
(e) C_1-6halogenlampe and
(f) ceanography,
X represents a carbon atom,
R³represents a
(1) C_1-6alkyl group optionally substituted by substituent(s)selected from
(a) C_1-6alkoxygroup,
(b) a 5-6-membered saturated aliphatic heterocyclic group containing an oxygen atom, and
(c) a hydroxyl group,
(2) C_3-8cycloalkyl group or
(3) a 5-6-membered saturated aliphatic heterocyclic group containing a nitrogen atom or an oxygen atom, optionally substituted by substituent(s)selected from
(a) C_1-6alkyl-carbonyl group,
(b) C_1-6alkoxy-carbonyl group,
(c) C_1-6alkylsulfonyl group and
(d) carbamoyl group, long is ina mono - or disubstituted by C _1-6alkyl group (or groups),
R⁴represents a
(1) a hydrogen atom, or
(2) C_1-6alkyl group,
R^5aand R^5beach independently represent
(1) a hydrogen atom, or
(2) C_1-6alkyl group, and
R⁶and R⁷each independently represent
(1) a hydrogen atom, or
(2) C_1-6alkyl group optionally substituted by substituent(s)selected from
(a) a hydroxyl group,
(b) C_1-6alkoxygroup and
(c) a 5-6-membered saturated aliphatic heterocyclic group containing 1 or 2 heteroatoms selected from nitrogen atom and oxygen atom, or
R⁶and R⁷not necessarily related to education, together with the nitrogen atom to which they relate, 5-6-membered saturated aliphatic heterocycle containing 1 or 2 heteroatoms selected from nitrogen atom and oxygen atom, optionally substituted by substituent(s)selected from
(a) the carbonyl group,
(b) ceanography and
(c) C_1-6halogenoalkanes group,
or its pharmaceutically acceptable salt.

8. The compound represented by the following formula (1)

where
R¹represents a
(1) a hydrogen atom,
(2) a halogen atom, or
(3) C_1-6alkyl group
(where R¹may be present as a substituent of the benzene iloperidone rings in any substitutable position on the ring);
L is a
(1) a simple link or
(2) -O-
(where L may be present as a substituent in position 5 or 6 of the condensed cycle);
R²represents a C_6-10aryl group (C_6-10aryl group optionally is condensed with C_3-6cycloalkanes), optionally substituted by substituent(s)selected from
(a) a halogen atom,
(b) C_1-6alkyl group,
(c) C_1-6halogenoalkanes group,
(d) C_1-6alkoxygroup,
(e) C_1-6halogenlampe and
(f) ceanography,
X represents a carbon atom,
R³represents a
(1) C_1-6alkyl group optionally substituted by substituent(s)selected from
(a) C_1-6alkoxygroup,
(b) a 5-6-membered saturated aliphatic heterocyclic group containing an oxygen atom, and
(c) a hydroxyl group,
(2) C_3-8cycloalkyl group or
(3) a 5-6-membered saturated aliphatic heterocyclic group containing a nitrogen atom or an oxygen atom, optionally substituted by substituent(s)selected from
(a) C_1-6alkyl-carbonyl group,
(b) C_1-6alkoxy-carbonyl group,
(c) C_1-6alkylsulfonyl group and
(d) carbamoyl group, optionally mono - or disubstituted by C_1-6alkyl group (or groups),
R⁴p is ecstasy a
(1) a hydrogen atom, or
(2) C_1-6alkyl group,
R^5aand R^5beach independently represent
(1) a hydrogen atom, or
(2) C_1-6alkyl group, and
R⁶and R⁷each independently represent
(1) a hydrogen atom, or
(2) C_1-6alkyl group optionally substituted by substituent(s)selected from
(a) a hydroxyl group,
(b) C_1-6alkoxygroup and
(c) a 5-6-membered saturated aliphatic heterocyclic group containing 1 or 2 heteroatoms selected from nitrogen atom and oxygen atom,
or its pharmaceutically acceptable salt.

9. The compound represented by the following formula (1)

where
R¹represents a
(1) a hydrogen atom, or
(2) a halogen atom
(where R¹may be present as a substituent of the benzene or pyridine ring at any substitutable position on the ring);
L is a
(1) a simple link or
(2) -O-
(where L may be present as a substituent in position 5 or 6 of the condensed cycle);
R²represents a phenyl group optionally substituted by substituent(s)selected from
(a) a halogen atom,
(b) C_1-6alkyl group,
(c) C_1-6halogenoalkanes group,
(d) C_1-6alkoxygroup,
(e) C_1-6halogenase is a system of groups and
(f) ceanography,
X represents a carbon atom,
R³represents a
(1) C_1-6alkyl group optionally substituted by substituent(s)selected from
(a) C_1-6alkoxygroup,
(b) a 5-6-membered saturated aliphatic heterocyclic group containing an oxygen atom, and
(c) a hydroxyl group, or
(2) C_3-8cycloalkyl group,
R⁴represents a hydrogen atom or methyl group,
R^5aand R^5beach independently represent a hydrogen atom, methyl group, ethyl group or isopropyl group, and
R⁶and R⁷represents a hydrogen atom,
or its pharmaceutically acceptable salt.

10. The compound represented by the following formula (1)

where
R¹represents a hydrogen atom,
L represents-O-
(where L may be present as a substituent in position 5 or 6 of the condensed cycle);
R²represents a phenyl group optionally substituted by substituent(s)selected from
(a) a halogen atom,
(b) C_1-6alkyl group,
(c) C_1-6halogenoalkanes group,
(d) C_1-6alkoxygroup,
(e) C_1-6halogenlampe and
(f) ceanography,
X represents a carbon atom,
R³represents a
(1) C_{1-6 alkyl group optionally substituted by substituent(s)selected from
(a) C1-6alkoxygroup,
(b) a 5-6-membered saturated aliphatic heterocyclic group containing an oxygen atom, and
(c) a hydroxyl group, or
(2) C3-8cycloalkyl group,
R⁴represents a hydrogen atom or methyl group, and
R^5aand R^5beach independently represent a hydrogen atom or methyl group, and
R⁶and R⁷represents a hydrogen atom,
or its pharmaceutically acceptable salt.}

11. N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}glycinamide,
N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-2-methylalanine,
N²-{[1-cyclopropyl-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[1-cyclobutyl-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[6-(4-chlorophenoxy)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[6-(4-pertenece)-1-(2-hydroxy-2-methylpropyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[6-(4-pertenece)-1-(3-methoxypropyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[6-(2-chloro-4-pertenece)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N² -{[1-ethyl-6-(4-methylphenoxy)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[6-(2,4-divergence)-1-(2-hydroxy-2-methylpropyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[1-(2-ethoxyethyl)-5-fluoro-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[1-ethyl-5-fluoro-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[1-(3-methoxypropyl)-6-(4-methylphenoxy)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[6-(4-methylphenoxy)-1-(tetrahydro-2H-Piran-4-yl)-1H-benzimidazole-2-yl]methyl}-L-alaninate,
N²-{[5-chloro-1-(2-ethoxyethyl)-6-(4-forfinal)-1H-benzimidazole-2-yl]methyl}-L-alaninate or
N²-{[5-chloro-6-(3,4-differenl)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate
or pharmaceutically acceptable salt of such compounds.

12. N²-{[1-(2-ethoxyethyl)-6-(4-pertenece)-1H-benzimidazole-2-yl]methyl}-2-methylalanine
or its pharmaceutically acceptable salt.

13. N²-{[6-(2-chloro-4-pertenece)-1-(2-ethoxyethyl)-1H-benzimidazole-2-yl]methyl}-L-alaninate or its pharmaceutically acceptable salt.

14. N²-{[1-ethyl-6-(4-methylphenoxy)-1H-benzimidazole-2-yl]methyl}-L-alaninate or its pharmaceutically acceptable salt.

15. N²-{[1-(3-methoxypropyl)-6-(4-methylphenoxy)-1H-benzimidazole-2-yl]methyl}-L-alaninate or its pharmaceutically acceptable salt.

16. N²-{[6-(4-methylphenoxy)-1-(tetrahydro-2H-Piran-yl)-1H-benzimidazole-2-yl]methyl}-L-alaninate or its pharmaceutically acceptable salt.

17. Medicine with any abscopal SNS properties suitable for the treatment or prevention of neuropathic pain, nociceptive pain, urination disorders or multiple sclerosis, which comprises the compound according to any one of claims 1 to 16 or its pharmaceutically acceptable salt as an active ingredient.

18. Inhibitor SNS, which is a compound according to any one of claims 1 to 16 or its pharmaceutically acceptable salt.

19. Pharmaceutical composition having any abscopal SNS properties, comprising the compound according to any one of claims 1 to 16 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.