CN101371833A - Use of 1-aryl-2(1H)-pyridinone compounds in preparing medicament for curing skin pruritus - Google Patents
Use of 1-aryl-2(1H)-pyridinone compounds in preparing medicament for curing skin pruritus Download PDFInfo
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- CN101371833A CN101371833A CNA2007101451253A CN200710145125A CN101371833A CN 101371833 A CN101371833 A CN 101371833A CN A2007101451253 A CNA2007101451253 A CN A2007101451253A CN 200710145125 A CN200710145125 A CN 200710145125A CN 101371833 A CN101371833 A CN 101371833A
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- pyridone
- trifluoromethyl
- methyl
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
Abstract
The invention relates to a drug application of 1-aryl-2(1H)-pyridone compound, in particular to an application of 1-aryl-2(1H)-pyridone compound in the preparation of a drug for curing skin pruritus. When being used for curing skin pruritus, 1-aryl-2(1H)-pyridone compound can be partially applied.
Description
Technical field
The present invention relates to the new medical usage of 1-aryl-2 (1H)-pyridinone compounds.
Background technology
Pruritus is a kind of response mechanism of self-protection under the body physiological state; it also is one of symptom of many systemic diseases and dermatosis; it can directly be caused by the skin chemical mediator; also can cause, and then cause peripheral nerve fiber even central nervous system's reaction by the variation of physical factor (as temperature).Although there is a lot of research to disclose nervous system, nerve fiber and multiple medium such as the effect in pruritus takes place such as neuropeptide, cytokine, pruritus is produced cutter system is still not fully aware of really.Existing technical research theory is thought: pruritus has special nerve conduction path, show that pruritus and pain are different independently sensation form (AndrewD, Craig A D.Spinothalamic lamina I neurons selectively sensitive to histamine; Acentral neural pathyway for itch.Nat Neurosci, 2001,4 (1): 72-77); Traditional pruritus medium produces pruritus as histamine, serotonin, acetylcholine etc. by stimulating C class nerve fiber; In addition, find also that in the dermal sensation nerve fiber opioid peptides is arranged, the receptor of pruritus medium such as vanillyl derivant exists, point out these media to mediate pruritus (Togashi y by receptors bind with the dermal sensation nerve fiber, U meuchiH.Okano K, et al.Antipruritic activity of the kapparopioid receptor agonist, TRK-820.Eur J pharmacol, 2002,435:259-264).
Clinical common pruritus is divided 4 types (Twycroddf R.Greace Handwerker H, etal.Itch:Scratching more than surface.QJM, 2003,96:7-26): (1) ends scabies factor susceptibility pruritus: originate from skin, because inflammation, drying or other skin injurys cause, are conducted by C class nerve fiber.(2) nerve pruritus disease is confined to cause pruritus by different afferent pathways on certain point, is the modal reason of this pruritus as neuropathy behind the herpes zoster.(3) neurogenic pruritus: originate from maincenter, but the sick foundation of learning of impassivity, as acting on the cholestasis pruritus that μ-opioid peptide receptor causes owing to opioid peptides.4. heart source property pruritus: as the paranoid state of parasitophobia disease.This classification is not only with clinical relevant but also comprised the information of the pathomechanism of pruritus.
In a single day patient suffers skin pruritus, usually can alleviate the symptom of pruritus by the behavior of scratching, and over-drastic scratching causes the release of inflammatory mediator, further causes pruritus, thereby forms vicious cycle, exacerbate inflammation or the infection of pruritus-scratch.Past, treatment skin scabies disease mainly is that system or topical application anti-inflammatory drug comprise that corticosteroid, systemic antihistaminic and immunosuppressant etc. suppress pruritus, but the antipruritic effect of these medicines is a secondary, follow antiinflammatory action and take place, and be not real antipruritic agent.And similar corticosteroid medication of whole body or topical application or antihistaminic usually can produce the side effect of not expecting.Make the skin lesion place that burn feeling be arranged as the similar corticosteroid medication of topical application, pruritus increases the weight of, the local scarlet patch etc. that occurs; Whole body is used antihistaminic, and that the patient occurs is drowsiness, malaise, giddy, untoward reaction such as absent minded.
Along with molecules basis, pathophysiology and the therapeutic research to relevant pruritus, to the further understanding of pruritus mechanism, at present, local selectivity antipruritic medicine has appearred.For example, according to the pruritus classification, the local application that is used for the treatment of pruritus susceptibility pruritus mainly contains capsaicin frost (WO2005117871) and doxepin (KR20050023057) etc.; KR20000046630, JP2006273783 etc. disclose some combination of compounds preparation and be used for the treatment of pruritus, and be good than the single component therapeutic effect; And the research of Chinese medicine also attempts to seek effective antipruritic good medicine, and CN1840169, CN1844114, CN1698719, CN1872149 etc. disclose respectively to be combined by kinds of traditional Chinese medicines and have been prepared into oral or external preparation such as decoction or lotion treatment pruritus in autumn, gynecological's pruritus or obstinate pruritus etc.Though some drugs has antipruritic effect preferably to the treatment of certain pruritus, but its potential untoward reaction has limited the application of such medicine, for example the antipruritic activity of chilli, capsaicin comes from it and contains the composition that makes pain nerve tip desensitization, it is all effective to the pruritus that the regional pruritus and the atoipc dermatitis of stubbornness causes, but makes its application limited owing to topical application has zest.Owing to the tricyclic compounds doxepin is the same with antihistaminic good unusually usefulness is arranged, be acknowledged as local antipruritic medicine.Yet this medicine percutaneous absorbs can produce sedation, so purposes is wideless.The evaluation of new Therapeutic Method is depended on the multidirectional judge of this symptom of pruritus and adopts quantitative method to draw and can carry out statistic analysis result.Though effectively therapeutic modality continues to bring out, the road for development of ideal antipruritic medicine is also very long.
Pyridine compounds is a huge family, has extensive physiologically active, has different physiologically actives owing to the group that is replaced on the pyridine ring is different.Comprise having parasite killing, antiinflammatory, fibrosis etc.
German patent DE 4343528 has reported that a class pyridinone compounds has insecticidal action on agricultural, have following structural formula I.
Structural formula I
A, B are all kinds of heterocycles such as furan nucleus, imidazoles, pyridine in the structure I, pyridone replaces; The chemical compound that has wherein comprised a class such as structural formula II.
Structural formula II
European patent EP 259048, EP367410, EP398499 have reported that a compounds has insecticidal action on agricultural, have the chemical compound of following structural formula II I.
Structural formula II I
Wherein comprised a class formation R
1Be pyridone, have the chemical compound of structural formula IV.
Structural formula IV
R wherein
10Be O or S.
European patent EP 216541 has reported that a compounds has insecticidal action on agricultural, has following structural formula V.
Structural formula V
Wherein Z represents halogen atom or haloform, X, and Y is selected from halogen atom
The chemical compound that has wherein comprised a class formation formula V:
Structural formula V
European patent EP 488220 has reported that a compounds has herbicide action, has following structural formula VI.
Structural formula VI
No matter these above chemical compounds are multiple, a plurality of substituent groups all to be arranged, complex structure on the phenyl ring of 1 of pyridine ring or pyridine ring in structure.
U.S. Pat 3839346A, US4052509A, US4042699 disclose 29 pyridine compounds with following structural VIII.
Structural formula VIII
And disclose this type of pyridone have antiinflammatory, analgesic, reduce effects such as serum uric acid level, pain relieving.Wherein, (5-methyl-1-phenyl-2 (1H)-pyridone) has best active and lower toxicity to 1-phenyl-5-methyl-2 (1H)-pyridone.
USP3839346 (1974.10.1 announcement) discloses the preparation method of some N-replacement 2-(1H)-pyridone.USP3947281 (1976.8.10 announcement), USP4042699 (1977.8.16) and USP3947281 (1977.10.4 announcement) have further described wherein a kind of chemical compound 5-methyl isophthalic acid-phenyl-2 (1H)-pyridone (Pirfenidone), the Chinese translation pirfenidone, this chemical compound can reduce uric acid and concentration of glucose in the blood plasma, is used for the treatment of people and mammiferous upper respiratory tract infection and skin infection.
U.S. Pat 5,310,562 have announced for the first time 1-phenyl-5-methyl-2 (1H)-pyridone in 1994, [5-methyl-1-phenyl-2 (1H)-pyridone] claims pirfenidone (Pirfenidone again, PFD) have the biological activity of fibrosis, described pirfenidone among the EP0383591 and be widely used aspect prevention and the treatment fibrotic disease.This medicine is a kind of oral active small molecular medicine, and by drugs approved by FDA, it is clinical that the treatment of the fibrotic disease of lung, kidney regulating liver-QI has been entered the II phase.U.S. Pat 5 subsequently, 518,729 and US5,716,632 declare that N-replaces-2 (1H)-pyridones [N-substituted2 (1H)-pyridone], be structural formula VIII, replace-3 (1H)-pyridones [N-substituted 3 (1H)-pyridone] with N-and also have the same anti-fibrosis effect of pirfenidone (Pirfenidone).And enumerated 44 chemical compounds, and major part wherein all is the known compound that draws from U.S. Pat 4052509, in these chemical compounds, and R
1, R
2, R
3, R
4All be limited to methyl or ethyl.Application number is to have related to the purposes of 1-aryl-5-methyl-2 (1H)-pyridinone compounds in the preparation anti-fibrosis medicine among CN200510031445.7 and the CN02114190.8.
The present application people is once at " Central South University's journal " (medicine) (2004,29 (2)) disclose chemical compound 1-(3-fluorophenyl)-5-methyl-2 (1H)-pyridone (AKF-PD) on to the fibroblastic cell experiment of kidney, shown that it has the effect that suppresses the kidney fibroblastic growth.
Application in other respects also has extensive studies to pirfenidone.For example, WO0/16775 has described and pirfenidone is used for the treatment of and has prevented dermatosis, the particularly pathological changes of fibrosis character, as the fibrosis damaged tissue, and wart contagious, contact dermatitis, burn and cicatrix etc.WO99/47140 has openly used 2-(1H)-pyridine compounds, particularly pirfenidone and has prepared partly sterilised's compositions, can be used for many surfaces (comprising skin surface etc.) antibacterial, fungus and/or virus are handled.WO01/62253 discloses and can use N-replacement 1-(1H)-pyridine compounds treatment epilepsy.CN1775212A discloses pirfenidone and has been used for the treatment of psoriasic application.
But, up to the present, 1-aryl-5-methyl-2 (1H)-pyridinone compounds is not used for the treatment of the report of skin pruritus as yet.
Summary of the invention
The new drug that the purpose of this invention is to provide class treatment skin pruritus.
The invention provides a kind of skin pruritus that is used for the treatment of, contain the medicine of 1-aryl-5-methyl-2-(1H) pyridinone compounds.
That is to say, the present invention relates to the application of 1-aryl-5-methyl-2-(1H) pyridinone compounds in the medicine of preparation treatment skin pruritus.
1-aryl-5-methyl-2 (1H)-pyridinone compounds is a micromolecular compound, and we find this compounds to the drying property skin pruritus in research process, and pruritus due to the atopic dermatitis etc. has stronger antipruritic effect and few side effects.
1-aryl-5-methyl-2-(1H) when pyridinone compounds is used for the treatment of skin pruritus, can be adopted the route of administration of topical application.
With the 1-aryl--when (1H) the pyridinone compounds part was on probation, the preparation that is adopted can be the external preparation of this area routine, comprises solution, cream, ointment, gel, washing liquid, suspendible or emulsion etc.No matter use which kind of dosage form, the 1-aryl-(1H) concentration of pyridinone compounds should be at about 0.1%-20% (wt/wt), and each amount of application is equivalent to about 1-5mg, every day 1-4 time.
Embodiment
Further specify the present invention below by specific embodiments.Described embodiment only is used for explanation or explains embodiment of the present invention, and can not limit protection scope of the present invention.
Embodiment 1
The animal model experiment of pirfenidone (or AKF-PD) treatment drying property skin pruritus.
60 of SD rats (male and female half and half) are divided into 6 groups at random, in the depilation of experiment right abdomen the previous day.Spread on the cotton balls part of soaking (mixed liquor of acetone and ether) during experiment and be stained with distilled water with cotton balls immediately behind the SD rat depilation place 15s and apply 30S, twice of every day (9:00 and 15:00), continuous 5 days in same part.
The administration group is: three dosage AKF-PD ointment groups, and 1 dosage pirfenidone ointment group, the blank group is: normal saline group and blank ointment base group.During the moulding, respective substance is smeared in rat skin depilation place timing every day (12:00), observes the spontaneous pruritus behavior of rat after 5 days; Each group of record is licked the number of times (continuously to lick body to minibreak occur, make lick body 1 time calculate) of precursor reactant in 20min respectively.Experimental result such as table 1, table 2.
Table 1 various dose AKF-PD or pirfenidone ointment cause influence (n=10, the X ± S) of drying property skin pruritus model to rat
*Compare P ∠ 0.05 with the ointment base matched group.
The result shows, compare with blank group (blank ointment base group or physiological water group), the body time number average significance of licking of the pirfenidone ointment group rat of the AKF-PD ointment machin 5% of 2%-10% reduces, and there was no significant difference between blank matrix group and the blank group, be ointment base to drying property skin pruritus unrestraint effect, medicine has in various degree inhibitory action to the drying property skin pruritus.
Embodiment 2
4-aminopyridine brings out mouse skin pruritus model
40 of kunming mices (male and female half and half) are divided into 3 groups at random, the depilation of medication back the previous day, and the administration group is: a dosage AKF-PD ointment group, 1 dosage pirfenidone ointment group, ointment base matched group.Subcutaneous injection 4-aminopyridine 1mg/kg is in depilation place behind preceding 3 groups of external medicine 30～40min.The normal control group is only injected 4-aminopyridine.Each group of record is licked the number of times (continuously to lick body to minibreak occur, make lick body 1 time calculate) of precursor reactant in 10min respectively.
Table 2 pair 4-aminopyridine brings out the influence that mice licks precursor reactant (n=10, X ± S)
* and ointment base matched group be P＜0.01 relatively.
5%AKF-PD ointment and 5%PFD ointment all can obviously suppress the mice that 4-aminopyridine (4-AP) brings out and lick precursor reactant, known 4-AP brings out mice and licks precursor reactant and skin mastocyte to discharge histamine relevant, this experiment shows, outside the Pass the itching-relieving action of AKF-PD ointment and PFD ointment may have with inhibition skin mastocyte release histamine.
Embodiment 3
The inductive skin pruritus model of 0.01% histamine phosphate
The inductive pruritus of 0.01% histamine phosphate, so that the threshold evaluation of itching: 30 of Cavia porcelluss are divided into 3 groups at random, the depilation of medication back the previous day, the administration group is: a dosage AKF-PD ointment group, 1 dosage pirfenidone ointment group, the ointment base matched group, the normal control group.Test the same day, abrade every Mus with coarse sandpaper and shave the area 1cm of hair place
2Each is organized repaste and smears medicine or blank ointment base 1 time, and about 10min begins to drip 0.01% 0.05ml of histamine phosphate at every Mus wound surface, later licks the back of the body until mice occurring.Later lick unlucky histamine phosphate's total itch-threshold of being given to begin occurring mice.
Table 3 histamine is to the tolerance experiment of itching
*Compare P＜0.01 with the normal control group.
5%AKF-PD ointment and 5%PFD ointment all can significantly improve itch-threshold.And compare significant difference with the normal control group.
Embodiment 4
Effect with AKF-PD/ pirfenidone Ointment in Treatment volunteer skin pruritus
The volunteer 1, man, 43 years old.Trouble skin pruritus autumn and winter 5 years, the dry pruritus of annual skin of leg autumn and winter once used multiple medicine and preserving moisture and protecting skin product invalid, and shank has slight breakage scratch.Winter one in 2006 lower limb uses 5%AKF-PD ointment, and a lower limb uses ointment base in contrast.After using a week, use the shank pruritus of 5%AKF-PD ointment obviously to alleviate, use pruritus disappearance after 10 days.And use the shank pruritus symptom of ointment base not have significant change.
The volunteer 2, man, 28 years old.Trouble skin pruritus autumn and winter 3 years, the dry pruritus of annual medial thigh skin autumn and winter once used multiple medicine and preserving moisture and protecting skin product invalid, and medial thigh skin produces ulcer because of scratching, pruritus serious symptom, influence sleep.Winters two in 2006 femoribus internus all uses 5%AKF-PD ointment to smear, and medication ulcer on the 3rd begins healing, the pruritus sx, and ulcer heals fully after 1 week, and the pruritus symptom disappears substantially.
Claims (6)
1.1-the application of aryl-2 (1H)-pyridinone compounds in the medicine of preparation treatment skin pruritus.
In the formula, R is alkyl, haloalkyl, carboxyl, carboxylic acid ester groups, methylol, aldehyde radical; A is phenyl ring, substituted benzene ring, naphthalene nucleus, replacement naphthalene nucleus, pyridine ring, substituted pyridines ring, pyrrole ring, substituted azole ring, quinoline ring, substd quinolines ring, imidazole ring, substituted imidazole ring.
Wherein preferred general formula is:
In the formula, R is alkyl, haloalkyl, carboxyl, carboxylic acid ester groups, methylol, aldehyde radical; R1, R2, R3, R4, R5 are hydrogen, alkyl, haloalkyl, carboxyl, carboxylic acid ester groups, hydroxyl, alkoxyl, amino, alkylamino, preferably chemical compound has:
1-(2-bromophenyl)-5-methyl-2-(1H) pyridone;
5-methyl isophthalic acid-(3-nitrobenzophenone)-2-(1H) pyridone,
5-methyl isophthalic acid-(4 '-methoxyphenyl)-2-(1H) pyridone,
5-methyl isophthalic acid-p-methylphenyl-2-(1H) pyridone,
5-methyl isophthalic acid-(3 '-trifluoromethyl)-2-(1H) pyridone,
5-ethyl-1-phenyl-2-(1H) pyridone,
5-methyl isophthalic acid-(3-nitrobenzophenone)-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, the 3-dibromo phenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 4-dibromo phenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 5-dibromo phenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 6-dibromo phenyl)-5-methyl-2-(1H) pyridone;
1-(3, the 4-dibromo phenyl)-5-methyl-2-(IH) pyridone;
1-(3, the 5-dibromo phenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 3-Dichlorobenzene base)-5-methyl-2-(1H) pyridone;
1-(2, the 4-Dichlorobenzene base)-5-methyl-2-(1H) pyridone;
1-(2, the 5-Dichlorobenzene base)-5-methyl-2-(1H) pyridone;
1-(2, the 6-Dichlorobenzene base)-5-methyl-2-(1H) pyridone;
1-(3, the 5-Dichlorobenzene base)-5-methyl-2-(1H) pyridone;
1-(2, the 3-difluorophenyl)-5-methyl-2-(1H) pyridone;
1-(2,4 difluorobenzene base)-5-methyl-2-(1H) pyridone;
1-(2, the 5-difluorophenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 6-difluorophenyl)-5-methyl-2-(1H) pyridone;
1-(3, the 5-difluorophenyl)-5-methyl-2-(1H) pyridone; Or
1-(2-trifluoromethyl)-5-methyl-2-(1H) pyridone;
1-(4-trifluoromethyl)-5-methyl-2-(1H) pyridone;
1-(2, the 3-trifluoromethyl)-5-methyl-2-(1H) pyridone;
1-(2, the 4-trifluoromethyl)-5-methyl-2-(1H) pyridone;
1-(2, the 5-trifluoromethyl)-5-methyl-2-(1H) pyridone;
1-(2, the 6-trifluoromethyl)-5-methyl-2-(1H) pyridone;
1-(3, the 4-trifluoromethyl)-5-methyl-2-(1H) pyridone;
1-(2, the 5-trifluoromethyl)-5-methyl-2-(1H) pyridone; Or
1-(2-aminomethyl phenyl)-5-methyl-2-(1H) pyridone;
1-(3-aminomethyl phenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 3-3,5-dimethylphenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 4-3,5-dimethylphenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 5-3,5-dimethylphenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 6-3,5-dimethylphenyl)-5-methyl-2-(1H) pyridone;
1-(3, the 4-3,5-dimethylphenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 5-3,5-dimethylphenyl)-5-methyl-2-(1H) pyridone; Or
1-(2-methoxyphenyl)-5-methyl-2-(1H) pyridone;
1-(3-methoxyphenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 3-Dimethoxyphenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 4-Dimethoxyphenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 5-Dimethoxyphenyl)-5-methyl-2-(1H) pyridone;
1-(2, the 6-Dimethoxyphenyl)-5-methyl-2-(1H) pyridone;
1-(3, the 4-Dimethoxyphenyl)-5-methyl-2-(1H) pyridone;
1-(3, the 5-Dimethoxyphenyl)-5-methyl-2-(1H) pyridone.
1-phenyl-5-trifluoromethyl-2-(1H) pyridone;
1-(2-pyridine radicals)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-pyridine radicals)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-pyridine radicals)-5-trifluoromethyl-2-(1H) pyridone;
1-(2-quinolyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-quinolyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-quinolyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2-pyrrole radicals)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-pyrrole radicals)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-imidazole radicals)-5-trifluoromethyl-2-(1H) pyridone;
1-(5-imidazole radicals)-5-trifluoromethyl-2-(1H) pyridone;
1-(2-aminomethyl phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-aminomethyl phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-aminomethyl phenyl)-5-trifluoromethyl-2-(1H) pyridone; Or
1-(2-fluorophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-fluorophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-fluorophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2-chlorphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-chlorphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-chlorphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2-bromophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-bromophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-bromophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2-iodophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-iodophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-iodophenyl)-5-trifluoromethyl-2-(1H) pyridone; Or
1-(2-methoxyphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-methoxyphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-methoxyphenyl)-5-trifluoromethyl-2-(1H) pyridone; Or
1-(2-carboxyl phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-carboxyl phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-carboxyl phenyl)-5-trifluoromethyl-2-(1H) pyridone; Or
1-(2-methoxycarbonyl group phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-methoxycarbonyl group phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-methoxycarbonyl group phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2-carbethoxy phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3-carbethoxy phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-carbethoxy phenyl)-5-trifluoromethyl-2-(1H) pyridone; Or
1-(23-dibromo phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 4-dibromo phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(25-dibromo phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(26-dibromo phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3, the 4-dibromo phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(35-dibromo phenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 3-Dichlorobenzene base)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 4-Dichlorobenzene base)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 5-Dichlorobenzene base)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 6-Dichlorobenzene base)-5-trifluoromethyl-2-(1H) pyridone;
1-(3, the 5-Dichlorobenzene base)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 3-difluorophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2,4 difluorobenzene base)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 5-difluorophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 6-difluorophenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3, the 5-difluorophenyl)-5-trifluoromethyl-2-(1H) pyridone; Or
1-(2-trifluoromethyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(4-trifluoromethyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 3-trifluoromethyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 4-trifluoromethyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 5-trifluoromethyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 6-trifluoromethyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3, the 4-trifluoromethyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 5-trifluoromethyl)-5-trifluoromethyl-2-(1H) pyridone; Or
1-(2, the 3-3,5-dimethylphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 4-3,5-dimethylphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 5-3,5-dimethylphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 6-3,5-dimethylphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3, the 4-3,5-dimethylphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 5-3,5-dimethylphenyl)-5-trifluoromethyl-2-(1H) pyridone; Or
1-(2, the 3-Dimethoxyphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 4-Dimethoxyphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 5-Dimethoxyphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(2, the 6-Dimethoxyphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3, the 4-Dimethoxyphenyl)-5-trifluoromethyl-2-(1H) pyridone;
1-(3, the 5-Dimethoxyphenyl)-5-trifluoromethyl-2-(1H) pyridone.
2. according to the said application of claim 1, it is characterized in that 1-aryl-2 (1H)-pyridinone compounds preferably from 1-phenyl-5-methyl-2 (1H)-pyridone, 1-(3-fluorophenyl)-5-methyl-2 (1H)-pyridone.
3. according to the said application of claim 1, it is characterized in that said skin pruritus is the pruritus due to drying property skin pruritus or the atopic dermatitis.
4. according to the said application of claim 1,2 or 3, it is characterized in that wherein said medicine is the medicine of local application.
5. according to the said application of claim 4, the medicine that it is characterized in that wherein said local application is solution, cream, ointment, gel, washing liquid, suspendible or emulsion etc.
6. according to the said application of claim 5, it is characterized in that the 1-aryl-(1H) concentration of pyridinone compounds should be at about 0.1%-20% (wt/wt), each amount of application is equivalent to about 1-5mg, every day 1-4 time.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101451253A CN101371833A (en) | 2007-08-23 | 2007-08-23 | Use of 1-aryl-2(1H)-pyridinone compounds in preparing medicament for curing skin pruritus |
| PCT/CN2008/071907 WO2009026816A1 (en) | 2007-08-23 | 2008-08-07 | The application of 1-aryl-2(1h)-pyridone compounds in preparation of medincines for treating itching of the skin |
| CN200880101039A CN101790375A (en) | 2007-08-23 | 2008-08-07 | The application of 1-aryl-2(1h)-pyridone compounds in preparation of medincines for treating itching of the skin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101451253A CN101371833A (en) | 2007-08-23 | 2007-08-23 | Use of 1-aryl-2(1H)-pyridinone compounds in preparing medicament for curing skin pruritus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101371833A true CN101371833A (en) | 2009-02-25 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101451253A Pending CN101371833A (en) | 2007-08-23 | 2007-08-23 | Use of 1-aryl-2(1H)-pyridinone compounds in preparing medicament for curing skin pruritus |
| CN200880101039A Pending CN101790375A (en) | 2007-08-23 | 2008-08-07 | The application of 1-aryl-2(1h)-pyridone compounds in preparation of medincines for treating itching of the skin |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200880101039A Pending CN101790375A (en) | 2007-08-23 | 2008-08-07 | The application of 1-aryl-2(1h)-pyridone compounds in preparation of medincines for treating itching of the skin |
Country Status (2)
| Country | Link |
|---|---|
| CN (2) | CN101371833A (en) |
| WO (1) | WO2009026816A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102149683A (en) * | 2009-05-25 | 2011-08-10 | 中南大学 | 1-(substituted benzyl)-5-trifluoromethyl-2-(1H) pyridone compounds and their salts, their preparation methods and use thereof |
| US8426407B2 (en) | 2009-05-25 | 2013-04-23 | Central South University | Preparation of 1-(substituted aryl)-5-trifluoromethyl-2-(1H)pyridone compounds and salts thereof and their applications |
| CN105085383A (en) * | 2015-08-19 | 2015-11-25 | 四川大学 | 5-methyl-2(1H)pyridone derivatives, and preparation method and application thereof |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2296653B1 (en) | 2008-06-03 | 2016-01-27 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| AR092742A1 (en) | 2012-10-02 | 2015-04-29 | Intermune Inc | ANTIFIBROTIC PYRIDINONES |
| CA2943363A1 (en) | 2014-04-02 | 2015-10-08 | Intermune, Inc. | Anti-fibrotic pyridinones |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4052509A (en) * | 1972-12-18 | 1977-10-04 | Affiliated Medical Research, Inc. | Method for reducing serum uric acid levels |
-
2007
- 2007-08-23 CN CNA2007101451253A patent/CN101371833A/en active Pending
-
2008
- 2008-08-07 CN CN200880101039A patent/CN101790375A/en active Pending
- 2008-08-07 WO PCT/CN2008/071907 patent/WO2009026816A1/en active Application Filing
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102149683A (en) * | 2009-05-25 | 2011-08-10 | 中南大学 | 1-(substituted benzyl)-5-trifluoromethyl-2-(1H) pyridone compounds and their salts, their preparation methods and use thereof |
| US8377932B2 (en) | 2009-05-25 | 2013-02-19 | Central South University | Preparation of 1-(substituted benzyl)-5-trifluoromethyl-2(1H)pyridone compounds and salts thereof and their applications |
| US8426407B2 (en) | 2009-05-25 | 2013-04-23 | Central South University | Preparation of 1-(substituted aryl)-5-trifluoromethyl-2-(1H)pyridone compounds and salts thereof and their applications |
| CN105085383A (en) * | 2015-08-19 | 2015-11-25 | 四川大学 | 5-methyl-2(1H)pyridone derivatives, and preparation method and application thereof |
| CN105085383B (en) * | 2015-08-19 | 2017-09-01 | 四川大学 | 5 methyl 2 (1H) Pyridione derivatives and its production and use |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101790375A (en) | 2010-07-28 |
| WO2009026816A1 (en) | 2009-03-05 |
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