WO2009026816A1

WO2009026816A1 - The application of 1-aryl-2(1h)-pyridone compounds in preparation of medincines for treating itching of the skin

Info

Publication number: WO2009026816A1
Application number: PCT/CN2008/071907
Authority: WO
Inventors: Lijian Tao; Gaoyun Hu; Jingsong Ding; Yanbin Zhou
Original assignee: Central South University
Priority date: 2007-08-23
Filing date: 2008-08-07
Publication date: 2009-03-05
Also published as: CN101790375A; CN101371833A

Abstract

The pharmaceutical application of 1-aryl-2(1H)-pyridone compounds, especially the application of 1-aryl-2(1H)-pyridone compounds in preparation of medicines for treating itching of the skin. The 1-aryl-2(1H)-pyridone compounds used to treat itching of the skin are administrated topically.

Description

1-aryl-2(1H)-pyridone compound

Application in the preparation of a medicament for treating skin pruritus

This invention relates to 1-aryl-2(1H)-pyridone compounds for use. Background technique

Itching is a reaction mechanism of self-protection in the physiological state of the body. It is also one of the symptoms of many systemic diseases and skin diseases. It can be caused directly by the chemical medium of the skin or by changes in physical factors (such as temperature). Causes the response of peripheral nerve fibers and even the central nervous system. Although many studies have revealed the role of the nervous system, nerve fibers, and various mediators such as neuropeptides and cytokines in the development of itching, the exact mechanism of itching is still not well understood. The current technical research theory holds that: Itching has a specific nerve conduction pathway, indicating that itching and pain are different independent sensory forms (Andrew D, Craig AD. Spinothalamic lamina I neurons selectively sensitive to histamine; a central neural pathyway for itch. Nat Neurosci, 2001, 4(l): 72-77); Traditional pruritic mediators such as histamine, serotonin, acetylcholine, etc. produce itching by stimulating Class C nerve fibers; in addition, opioids are also found in skin sensory nerve fibers. The presence of receptors for itch mediators such as peptides and vanillyl derivatives suggests that these mediators may mediate pruritus by binding to receptors in the skin's sensory nerve fibers (Togashi y, U meuchi H. Okano K, et al. Antipruritic activity of the kapparopioid Receptor agonist, TR -820. Eur J pharmacol, 2002, 435: 259-264)

Common clinical itching is divided into 4 types (; Twycroddf R.Greace Handwerker H, et al. Itch: Scratching more than surface.QJM, 2003, 96:7-26): (1) sputum factor susceptibility pruritus: originated from the skin Conducted by Class C nerve fibers due to inflammation, dryness, or other skin damage. (2) Neurotic pruritus is limited to a certain point, causing itching through different afferent pathways, such as post-herpetic neuropathy, which is the most common cause of this itching. (3) Neurogenic pruritus: originated from the central, but no neurological basis, such as cholestatic pruritus caused by opioid peptides acting on the μ-opioid peptide receptor. 4 cardiogenic itching: such as the delusional state of parasitic phobia. This classification is both clinically relevant and contains information on the pathological mechanisms of itching. Once the patient suffers from itchy skin, it often relieves the symptoms of itching by scratching, and excessive scratching causes the release of inflammatory mediators, which further causes itching, thereby forming a vicious cycle of itching-scratching, aggravating inflammation or infection. In the past, the treatment of cutaneous snoring was mainly caused by systemic or topical anti-inflammatory drugs including corticosteroids, systemic antihistamines and immunosuppressants, but the anti-itch effect of these drugs was only secondary, accompanied by anti-inflammatory effects. What happens is not really anti-itch drugs. Systemic or topical application of corticosteroid-like or antihistamines often produces undesirable side effects. For example, local application of corticosteroid-like drugs causes burning sensation in the skin lesions, increased itching, and localized red erythema. Systemic antihistamines, patients with drowsiness, general malaise, dizziness, inattention and other adverse reactions.

With the study of the molecular basis, pathophysiology and therapeutics of itching, and further understanding of the mechanism of pruritus, local selective anti-itch drugs have emerged. For example, according to the pruritus classification, topical medications for the treatment of itching pruritus are mainly capsicum cream (WO2005117871) and doxepin (KR20050023057), etc.; KR20000046630, JP2006273783, etc. disclose the preparation of certain combination compounds for the treatment of itching, The single-component treatment has a good effect; while the traditional Chinese medicine research also tries to find an effective anti-itch medicine, CN1840169, CN1844114, CN1 698719 CN1872149, etc. respectively disclose the preparation of a soup or lotion by oral combination of multi-flavor Chinese medicine or Topical preparations for the treatment of autumn itching, gynecological itching or intractable itching. Although some drugs have a good antipruritic effect on the treatment of certain itching, its potential adverse reactions limit the application of such drugs. For example, the anti-itch activity of dried chili and capsaicin stems from the fact that it contains pain-relieving nerves. The desensitizing component of the distal end, which is effective for stubborn localized itching and itching caused by atopic dermatitis, but its application is limited due to the irritancy of topical application. Because the tricyclic compound doxepin has the same excellent efficacy as antihistamines, it has been recognized as a topical anti-itch drug. However, this drug can produce a sedative effect by percutaneous absorption, so it is not widely used. The evaluation of the new treatment method relies on the multi-directional evaluation of the symptom of itching and the use of quantitative methods to obtain statistical analysis results. Although effective treatments continue to emerge, the ideal anti-itch drug development path is still very long.

Pyridone compounds are a large family with a wide range of physiological activities and different physiological activities due to the different groups substituted on the pyridine ring. Including insecticidal, anti-inflammatory, anti-fibrotic and the like.

German Patent DE 4343528 reports that a class of pyridone compounds has an insecticidal action in agriculture and has the following structural formula I.

Structural formula I

In Structure 1, B is a heterocyclic ring such as a furan ring, an imidazole, a pyridine or a pyridone; and a compound of the formula II is contained therein.

European Patent Nos. EP 259048, EP 367410, and EP 398499 report a class of compounds which have an insecticidal action in agriculture and have the following compounds of formula III.

Structural formula III

It contains a class of compounds having the structure of pyridone and having the formula IV. Structural formula IV

Among them Ri. It is 0 or 8.

European Patent EP 21 6541 reports that a class of compounds has an insecticidal action in agriculture and has the following structural formula.

Structural formula V

Wherein z represents a halogen atom or a trihalomethane, and X, Y is selected from a halogen atom which comprises a compound of the formula V:

Structural form V

European Patent EP 488 220 reports that a class of compounds has a herbicidal action and has the following structural formula VI.

Structural VI

The above compounds have various structures and multiple substituents in the structure, whether it is a pyridine ring or a benzene ring at the 1-position of the pyridine ring, and the structure is complicated.

U.S. Patent No. 3,839,346, A, US Pat.

Structural formula VIII

It also discloses that such pyridone has anti-inflammatory, antipyretic, lowering serum uric acid levels, and relieving pain. Among them, 1-phenyl-5-methyl-2(1H)-pyridone has the best activity and low toxicity. A process for the preparation of certain N-substituted 2-(1H)-pyridones is disclosed in USP 3,839,346, issued to 1974. Further, one of the compounds 5-methyl-1-phenyl-2(1H)- is described in USP 3,947,281 (published in 1976.8, 10), USP 4042699 (1977.8, 16) and USP 3,943,281 (published in 1977.10). Pirfenidone, Chinese translation of pirfenidone, which lowers plasma uric acid and glucose concentrations for the treatment of upper respiratory tract infections and skin infections in humans and mammals.

U.S. Patent 5,310,562 first published 1-phenyl-5-methyl-2(1H)-pyridone in 1994.

[5-methyl- 1 -phenyl-2(lH)-pyridone] Also known as pirfenidone (PFD) has anti-fibrotic biological activity, and EP0383591 describes pirfenidone in the prevention and treatment of fibrotic diseases. There are a wide range of applications. The drug is an oral active small molecule drug approved by the US FDA. The treatment of fibrotic diseases of the lungs, kidneys and liver has entered Phase II clinical trials. U.S. Patent No. 5,518,729 and U.S. Patent No. 5,716,632, the disclosure of which is incorporated herein by reference.

VIII, and N-substituted -3(1H)-pyridone [N-substituted 3(1H)-pyridone] also has pirfenidone

(Pirfenidone) - like anti-fibrotic effect. And 44 compounds are listed, most of which are known compounds of U.S. Patent No. 4,052,509, in which R ₂ , R ₃ are all defined as methyl or ethyl. The application numbers of CN200510031445. 7 and CN02114190. 8 relate to the use of 1-aryl-5-methyl-2(1H)-pyridone compounds in the preparation of anti-fibrotic drugs.

The inventor of the present application disclosed the compound 1-(3-fluorophenyl)-5-methyl-2(1H)-pyridinone (Journal of Central South University (Medical Edition) (2004, 29(2)). AKF-PD) Cellular experiments on renal fibroblasts have been shown to inhibit the growth of renal fibroblasts.

There are also extensive studies on the use of pirfenidone in other applications. For example, W000/16775 describes the use of pirfenidone for the treatment and prevention of skin lesions, particularly fibrotic lesions such as fibrotic tissue, contagious sputum, contact dermatitis, burns and scars. W099/47140 discloses the use of 2-(1H)-pyridones, in particular pirfenidone, for the preparation of topical disinfecting compositions for the treatment of bacteria, fungi and/or viruses on many surfaces, including skin surfaces and the like. . W001/62253 discloses the use of N-substituted 1-(1H)-pyridones for the treatment of epilepsy. CN1775212A discloses the use of pirfenidone for the treatment of psoriasis.

However, up to now, 1-aryl-5-methyl-2(1H)-pyridone compounds have not been used for the treatment of skin itching. Summary of the invention

It is an object of the present invention to provide a new class of drugs for treating itchy skin.

The present invention provides a medicament comprising a 1-aryl-5-methyl-2-(1indolyl)pyridinone compound for treating pruritus of the skin.

That is, the present invention relates to the use of a 1-aryl-5-methyl-2-(1?)pyridone compound for the preparation of a medicament for treating pruritus.

The 1-aryl-5-methyl-2(1H)-pyridone compound is a small molecule compound. During the research, we found that the compound has strong itch on dry skin, itching caused by specific dermatitis, etc. Itching effect, and fewer side effects.

When a 1-aryl-5-methyl-2-(1?)pyridone compound is used for the treatment of pruritus, a topical route of administration can be employed.

When the 1-aryl-(1H)pyridone compound is topically tested, the preparation to be used may be a conventional preparation conventionally used in the art, including solutions, creams, ointments, gels, lotions, suspensions or emulsions and the like. Regardless of the dosage form used, the concentration of the 1-aryl-(1H)pyridone compound should be in the range of about 0.1% to 20% (wt/wt), and the amount of each application is equivalent to about 1-5 mg per day, 1- 4 times.

Example

The invention is further illustrated by the following specific embodiments. The examples are only intended to illustrate or explain the embodiments of the invention, and do not limit the scope of the invention.

Example 1

An animal model of pirfenidone (or AKF-PD) for the treatment of dry skin itching.

Sixty SD rats (female and half) were randomly divided into 6 groups, and the right abdomen was depilated one day before the experiment. During the experiment, a cotton ball soaked (mixture of acetone and ether) was applied to the hair removal area of SD rats for 15 s. Immediately after applying the cotton ball to distilled water for 30S, twice a day (9: 00 and 15: 00) , for 5 consecutive days.

The administration group was: three doses of AKF-PD ointment group, one dose of pirfenidone ointment group, and blank control group: saline group and blank ointment matrix group. During the modeling period, the rat skin hair removal site was applied regularly (12: 00) every day, and the rats were observed for spontaneous itching behavior after 5 days. The number of carcass reactions in each group was recorded within 20 min (from continuous carcass to short-lived). Pause, for the body 1 calculation). The experimental results are shown in Table 1, Table 2.

Table 1 Effect of different doses of AKF-PD or pirfenidone ointment on dry skin itching model in rats (n=10, X Shi S) Number of group reactions in the number group (number of times / 20min) inhibition rate (%)

1 2% AKF-PD ointment group 1.9±1.9** 78.36

2 5% AKF-PD ointment group 1.5±1.4** 88.2

3 10% AKF-PD ointment group 1.4±1.3** 92.1

4 5% pirfenidone ointment group 0.9±1.4** 93.2

5 ointment matrix control group 4.5±3.6

6 saline control group 5.4±4.3

**Compared with ointment base control group PZ0.05. The results showed that compared with the blank control group (blank ointment base group or physiological water group), the number of carcasses of 2%-10% AKF-PD ointment and 5% pirfenidone ointment group was significantly decreased. There was no significant difference between the blank matrix group and the blank control group, that is, the ointment matrix had no inhibitory effect on dry skin itching, and the drug had different degrees of inhibition on dry skin itching.

Example 2

4-aminopyridine induced skin itch model in mice

Forty Kunming mice (male and female) were randomly divided into 3 groups. The back of the day was depilated. The administration group was: one dose AKF-PD ointment group, one dose pirfenidone ointment group, ointment matrix control group. The first 3 groups were applied externally for 30~40 min, and then subcutaneously injected with 4-aminopyridine lmg/kg at the hair removal site. The normal control group was only injected with 4-aminopyridine. The number of carcass reactions in each group was recorded in 10 min (from continuous carcass to short pause, and one carcass calculation).

Table 2 Effect of 4-aminopyridine-induced steroidal response in mice (n=10, X±S)

Group number of carcass reactions (number of times / lOmin) inhibition rate (%)

5% AKF-PD ointment group 1.5±1.7** 92.8

5% PFD ointment group 1.5±1.4** 93.4

Ointment matrix control group 21.4±5.3

Normal control group 30.9±6.4

**Compared with ointment base control group P<0.01.

Both 5% AKF-PD ointment and 5% PPD ointment can significantly inhibit 4 - aminopyridine (4-AP)-induced steroidal response in mice. It is known that 4 - AP induces steroid reaction in mice and release of histamine from skin mast cells. related, This experiment shows that the antipruritic effect of AKF-PD ointment and PFD ointment may be related to the inhibition of histamine release from skin mast cells. Example 3

0. 01% histamine-induced skin itching model

0. 01% histamine induced pruritus, so that the itch threshold was evaluated: 30 guinea pigs were randomly divided into 3 groups, and the back of the day was depilated. The administration group was: one dose of AKF-PD ointment, one dose of pirfenib Ketone ointment group, ointment base control group, normal control group. On the day of the experiment, the area of the shaving area of each mouse was rubbed with coarse sandpaper by 1 cm ² . Each group was re-applied with a drug or a blank ointment base once, and about 0.01 min was applied to each mouse wound for 0. 01% of histamine phosphate 0. 05 ml until the mouse turned back. The itch threshold was calculated by starting the total amount of histamine phosphate administered when the mouse turned back. Table 3 Histamine to itch tolerance test

Group dose (mg. L" ¹ ) histamine-induced itch threshold (u g. L -

5% AKF-PD ointment group 18 305.4士 15.0

5% PFD ointment group 20 354.3士 45.2** Ointment matrix control group 1 35.4士15.2

Normal control group 25.4 ± 17.9

**Compared with normal control group P<0.01.

Both 5% AKF-PD ointment and 5% PFD ointment significantly increased the itch threshold. And the difference was significant compared with the normal control group. Example 4

Treatment of skin itching in volunteers with AKF-PD/pirfenidone ointment

Volunteer 1, male, 43 years old. Suffering from itching skin in autumn and winter for 5 years, the skin of the calf is dry and itchy every autumn and winter. It has been used in various medicines and moisturizing skin care products, and the calf has slight broken scratches. In the winter of 2006, 5% AKF-PD ointment was used in one leg, and ointment base was used as a control in one leg. After one week of use, the itching of the calves with 5% AKF-PD ointment was significantly relieved, and itching disappeared after 10 days of use. There was no significant change in the itching of the calves using the ointment base. Volunteer 2, male, 28 years old. Suffering from itching skin in autumn and winter for 3 years, the skin inside and outside the thigh is dry and itchy every autumn and winter. It has been used in various medicines and moisturizing skin care products. The inner thigh skin has ulcers due to scratching, and the itching symptoms are serious, which affects sleep. In the winter of 2006, both sides of the two thighs were smeared with 5% AKF-PD ointment. The ulcer began to heal on the 3rd day, and the itching symptoms were alleviated. After 1 week, the ulcer completely healed and the itching symptoms basically disappeared.

Claims

Claim

l. Use of a 1-aryl-2(m)-pyridone compound for the preparation of a medicament for treating pruritus of the skin.

In the formula, R is an alkyl group, a halogenated alkyl group, a carboxyl group, a carboxylate group, a methylol group or an aldehyde group; A is a benzene ring, a substituted benzene ring, a naphthalene ring, a substituted naphthalene ring, a pyridine ring, a substituted pyridine ring, a pyrrole ring And substituted pyrrole ring, quinoline ring, substituted quinoline ring, imidazole ring, substituted imidazole ring.

Among the preferred formulas are:

Wherein R is alkyl, haloalkyl, carboxyl, carboxylate, hydroxymethyl, aldehyde; Rl, R2, R3, R4, R5 are hydrogen, alkyl, alkyl, carboxyl, carboxylic acid ester Base, hydroxyl, alkoxy, amino, alkylamino, preferred compounds are:

1-(2-bromophenyl)-5-methyl-2-(1H)pyridone;

5-methyl-1-(3-nitrophenyl)-2-(1H)pyridone,

5-methyl-1-(4'-methoxyphenyl)-2-(1H)pyridone,

5-methyl-1-p-tolyl-2-(1H)pyridone,

5-methyl-1-(3'-trifluoromethylphenyl)-2-(1H)pyridone,

5-ethyl-1-phenyl-2-(1H)pyridone,

5-methyl-1-(3-nitrophenyl)-2-(1H)pyridone.

1 - ( 2 -bromophenyl) - 5 -methyl-2 - (1H) pyridone

1 - ( 3 -bromophenyl) - 5 -methyl-2 - (1H) pyridone

1 - ( 4 -bromophenyl) - 5 -methyl-2 - (1H) pyridone or

1 - (2-fluorophenyl)-5-methyl-2 - (1H) pyridone

1 - ( 3 -fluorophenyl) - 5 -methyl-2 - (1H) pyridone

1 - ( 4 -fluorophenyl) - 5 -methyl-2 - (1H) pyridone or

1 - ( 2 -iodophenyl) - 5 -methyl-2 - (1H) pyridone

1 - ( 3 -iodophenyl) - 5 -methyl-2 - (1H) pyridone

1 - ( 4 -iodophenyl) - 5 -methyl-2 - (1H) pyridone or 1 - (2,3-dibromophenyl)-5-methyl-2 - (1H)pyridone

1 - (2,4-dibromophenyl)-5-methyl-2 - (1H)pyridone

1 - (2,5-dibromophenyl)-5-methyl-2 - (1H) pyridone

1 - (2,6-dibromophenyl)-5-methyl-2 - (1H) pyridone

1 - (3,4-dibromophenyl)-5-methyl-2 - (1H) pyridone

1 - (3,5-dibromophenyl)-5-methyl-2 - (1H) pyridone

1 - (2,3-dichlorophenyl)-5-methyl-2 - (1H) pyridone

1 - (2,4-dichlorophenyl) - 5 -methyl-2 - (1H) pyridone

1 - (2,5-dichlorophenyl) - 5 -methyl-2 - (1H) pyridone

1 - (2,6-dichlorophenyl)-5-methyl-2 - (1H) pyridone

1 - (3,5-dichlorophenyl)-5-methyl-2 - (1H) pyridone

1 - (2,3-difluorophenyl) - 5 -methyl-2 - (1H) pyridone

1 - (2,4-difluorophenyl) - 5 -methyl-2 - (1H) pyridone

1 - (2,5-difluorophenyl) - 5 -methyl-2 - (1H) pyridone

1 - (2,6-difluorophenyl) - 5 -methyl-2 - (1H) pyridone

1 - (3,5-difluorophenyl) - 5 -methyl-2 - (1H) pyridone

1-(2-trifluoromethylphenyl)-5-methyl-2-(1H)pyridinone; 1-(4-trifluoromethylphenyl)-5-methyl-2-(1H)pyridine ketone;

1 - (2,3-trifluoromethylphenyl)-5-methyl-2 - (1H)pyridone

1 - (2,4-trifluoromethylphenyl)-5-methyl-2 - (1H) pyridone

1 - (2,5-trifluoromethylphenyl)-5-methyl-2 - (1H) pyridone

1 - (2,6-trifluoromethylphenyl)-5-methyl-2 - (1H) pyridone

1-(3,4-Trifluoromethylphenyl)-5-methyl-2 - (1H)pyridone

1 - (2,5-trifluoromethylphenyl)-5-methyl-2 - (1H) pyridone

1-(2-methylphenyl)-5-methyl-2-(1H)pyridone;

1-(3-methylphenyl)-5-methyl-2-(1H)pyridinone;

1 - (2,3-dimethylphenyl)-5-methyl-2-(1H)pyridinone; 1 - (2,4-dimethylphenyl)-5-methyl-2- (1H Pyridone; 1 - (2,5-dimethylphenyl)-5-methyl-2-(1H)pyridinone; 1 - (2,6-dimethylphenyl)-5-methyl- 2-(1H)pyridone; 1 - (3,4-dimethylphenyl)-5-methyl-2-(1H)pyridinone; 1 - (2,5-dimethylphenyl) -5 -methyl-2-(1H)pyridone; or 1-(2-methoxyphenyl)-5-methyl-2-(1H)pyridinone; 1-(3-methoxyphenyl)- 5-methyl-2-(1H)pyridone;

1-(2,3-dimethoxyphenyl)-5-methyl-2-(1H)pyridone;

1-(2,4-dimethoxyphenyl)-5-methyl-2-(1H)pyridone;

1-(2,5-dimethoxyphenyl)-5-methyl-2-(1H)pyridone;

1-(2,6-dimethoxyphenyl)-5-methyl-2-(1H)pyridone;

1-(3,4-dimethoxyphenyl)-5-methyl-2-(1H)pyridone;

1-(3,5-Dimethoxyphenyl)-5-methyl-2-(1H)pyridone.

1-phenyl-5-trifluoromethyl-2(1H)pyridone;

1-(2-pyridyl)-5-trifluoromethyl-2-(1H)pyridinone 1-(3-pyridyl)-5-trifluoromethyl-2-(1H)pyridinone 1- (4 -pyridyl)-5-trifluoromethyl-2-(1H)pyridone -(2-quinolinyl)-5-trifluoromethyl-2(1H)pyridone

- (3-quinolinyl)-5-trifluoromethyl-2(1H)pyridone

- (4-quinolinyl)-5-trifluoromethyl-2(1H)pyridone

- (2-pyrrolyl)-5-trifluoromethyl-2(1H)pyridone

- (3-pyrrolyl)-5-trifluoromethyl-2(1H)pyridone

- (4-imidazolyl)-5-trifluoromethyl-2(1H)pyridone

- (5-imidazolyl)-5-trifluoromethyl-2(1H)pyridone

(2-methylphenyl)-5-trifluoromethyl-2-(1H)pyridone;

(3-methylphenyl)-5-trifluoromethyl-2-(1H)pyridone;

(4-methylphenyl)-5-trifluoromethyl-2(1H)pyridone;

2 murine base) -5-trifluoromethyl-2(1H)pyridone

3 fluorophenyl ) -5-trifluoromethyl -2 (1H) pyridone

4-fluorophenyl)-5-trifluoromethyl-2(1H)pyridone

2-chlorophenyl)-5-trifluoromethyl-2(1H)pyridone

3-chlorophenyl)-5-trifluoromethyl-2(1H)pyridone

4-chlorophenyl)-5-trifluoromethyl-2(1H)pyridone

2-bromophenyl)-5-trifluoromethyl-2(1H)pyridone

3-bromophenyl)-5-trifluoromethyl-2(1H)pyridone

4-bromophenyl)-5-trifluoromethyl-2(1H)pyridone

2-iodophenyl)-5-trifluoromethyl-2(1H)pyridone

3-iodophenyl)-5-trifluoromethyl-2(1H)pyridone

4-iodophenyl)-5-trifluoromethyl-2(1H)pyridone

2-methoxyphenyl)-5-trifluoromethyl-2-(1H)pyridone;

3-methoxyphenyl)-5-trifluoromethyl-2-(1H)pyridinone; (4-methoxyphenyl)-5-trifluoromethyl-2-(1H)pyridone; or (2-carboxyphenyl)-5-trifluoromethyl-2-(1H)pyridinone; (3-carboxyphenyl)-5-trifluoromethyl-2(1H)pyridinone; (4-carboxybenzene -5-trifluoromethyl-2-(1H)pyridinone; or (2-methoxycarbonylphenyl)-5-trifluoromethyl-2(1H)pyridinone; (3-methoxycarbonylbenzene -5-trifluoromethyl-2(1H)pyridinone; (4-methoxycarbonylphenyl)-5-trifluoromethyl-2-(1H)pyridinone; (2-ethoxycarbonylphenyl) ) - 5 -trifluoromethyl-2 (1H) pyridone;

(3-ethoxycarbonylbenzene:yl)-5-trifluoromethyl-2(1H)pyridinone; (4-ethoxycarbonylphenyl) 5-trifluoromethyl-2-(1H)pyridone; or

(2,3-dibromophenyl)-5-trifluoromethyl-2 - (1H)pyridone

(2,4-dibromophenyl)-5-trifluoromethyl-2 - (1H)pyridone

(2,5-dibromophenyl)-5-trifluoromethyl-2 - (1H)pyridone

(2,6-dibromophenyl)-5-trifluoromethyl-2 - (1H)pyridone

(3,4-dibromophenyl)-5-trifluoromethyl-2 - (1H)pyridone

(3,5-dibromophenyl)-5-trifluoromethyl-2 - (1H)pyridone

(2,3-dichlorophenyl)-5-trifluoromethyl-2 - (1H)pyridone

(2,4-dichlorophenyl)-5-trifluoromethyl-2-(1H)pyridone

(2,5-dichlorophenyl)-5-trifluoromethyl-2 - (1H) pyridone 1 - (2,6-dichlorophenyl)-5-trifluoromethyl-2-(1H)pyridone

1 - (3,5-dichlorophenyl)-5-trifluoromethyl-2-(1H)pyridone

1-(2,3-difluorophenyl)-5-trifluoromethyl-2-(1H)pyridone

1-(2,4-difluorophenyl)-5-trifluoromethyl-2-(1H)pyridone

1 - (2,5-difluorophenyl)-5-trifluoromethyl-2-(1H)pyridone

1 - (2,6-difluorophenyl)-5-trifluoromethyl-2-(1H)pyridone

1 - (3,5-difluorophenyl) - 5 -trifluoromethyl -2 - (1H) pyridone or

1-(2-fluorenylmethylphenyl)-5-trifluoromethyl-2-(1H)pyridone;

1-(4-fluorenylfluoromethylphenyl)-5-trifluoromethyl-2-(1H)pyridone;

1-(2,3-trifluoromethylphenyl)-5-trifluoromethyl-2 - (1H)pyridone

1-(2,4-trifluoromethylphenyl)-5-trifluoromethyl-2 - (1H)pyridone

1-(2,5-trifluoromethylphenyl)-5-trifluoromethyl-2 - (1H)pyridone

1 - (2,6-trifluoromethylphenyl)-5-trifluoromethyl-2 - (1H) pyridone

1-(3,4-Trifluoromethylphenyl)-5-trifluoromethyl-2 - (1H)pyridone

1 - (2,5-trifluoromethylphenyl)-5-trifluoromethyl-2 - (1H) pyridone or

1 - (2,3-dimethylphenyl)-5-trifluoromethyl-2(1H)pyridone

1 - (2,4-dimethylphenyl)-5-trifluoromethyl-2(1H)pyridone

1 - (2,5-dimethylphenyl)-5-trifluoromethyl-2-(1H)pyridone

1 - (2,6-dimethylphenyl)-5-trifluoromethyl-2-(1H)pyridone

1-(3,4-dimethylphenyl)-5-trifluoromethyl-2(1H)pyridone

1 - (2,5-dimethylphenyl)-5-trifluoromethyl-2-(1H)pyridone or

1-(2,3-Dimethoxyphenyl)-5-trifluoromethyl-2 - (1H)pyridone

1 - (2,4-dimethoxyphenyl)-5-trifluoromethyl-2 - (1H) pyridone

1 - (2,5-dimethoxyphenyl)-5-trifluoromethyl-2 - (1H) pyridone

1 - (2,6-dimethoxyphenyl)-5-trifluoromethyl-2 - (1H) pyridone

1-(3,4-Dimethoxyphenyl)-5-trifluoromethyl-2-(1H)pyridone

1 - (3,5-Dimethoxyphenyl)-5-trifluoromethyl-2-(1H)pyridone.

2. Use according to claim 1, characterized in that the 1-aryl-2(1H)-pyridone compound is preferably self-organic-phenyl-5-methyl-2(1Η)-pyridone, 1_ (3) -Fluorophenyl)-5-methyl-2(1H)-pyridone.

3. Use according to claim 1, characterized in that the pruritus is pruritus caused by dry skin itching or specific dermatitis.

4. Use according to claim 1, 2 or 3, characterized in that the medicament is a locally administered medicament.

5. The use according to claim 4, wherein the locally administered drug is a solution, a cream, an ointment, a gel, a lotion, a suspension or an emulsion, and the like.

6. The use according to claim 5, characterized in that the concentration of the 1-aryl-(1H)pyridone compound should be in the range of about 0.1% to 20% (wt/wt), and the amount per application is equivalent to about 1 5 mg, 1_4 times a day.