CN103405439B - Application of pyrimidine compound to preparing antifungal medicines - Google Patents
Application of pyrimidine compound to preparing antifungal medicines Download PDFInfo
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- CN103405439B CN103405439B CN201310332525.0A CN201310332525A CN103405439B CN 103405439 B CN103405439 B CN 103405439B CN 201310332525 A CN201310332525 A CN 201310332525A CN 103405439 B CN103405439 B CN 103405439B
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Abstract
The invention relates to the technical field of application of pyrazolopyrimidine compounds to preparing medicines for diseases infected by cryptococcus neoformans and aims to provide application of a pyrazolopyrimidine compound. In order to achieve the aim, the invention adopts the technical scheme that the pyrazolopyrimidine compound is N3-(4-fluorophenyl)-1H-pyrazolo[3,4-D]pyrimidine-3,4-diamine. According to the invention, the compound has a favorable antifungal activity on various superficial and deep fungi, has the advantages of high efficacy, low toxicity, wide antifungal spectrum and the like as compared with the conventional clinical antifungal medicines, and can be used for preparing antifungal medicines.
Description
Technical field
The present invention relates to the application of a kind of compound, specifically, is the application about a kind of throat azoles miazines compound.
Background technology
The position that fungal infectious disease invades human body according to fungus is divided into 4 classes: Superficial mycoses, dermatomycosis, subcutaneous mycosis and systemic mycoses; The former two is collectively referred to as superficial mycosis, and the latter two are also called deep mycosis.Fungal infectious disease is divided into following several according to fungal infection difference: candida albicans bacterium infectious disease, Candida parapsilosis bacterium infectious disease, Candida glabrata infectious disease, infection by Cryptococcus neoformans disease, Gypsum Fibrosum shape sporidiole bacteria infectious disease, trichophyton infectious disease, aspergillus fumigatus infection disease.
In recent years, along with the extensive use of broad ectrum antibiotic, corticosteroid and immunosuppressant, advanced Clinics is as the popularization of organ transplantation etc., AIDS's is popular, and the impact of tumor Radiotherapy chemotherapy, cause fungal infection particularly deep fungal infection significantly rise, deep fungal infection has now become the major disease such as acquired immune deficiency syndrome (AIDS) and tumor main causes of death.
The nitrogen azole compounds reported at present and commonly use clinically has ketoconazole (Ketoconazole, KCZ), fluconazol (Fluconazole, FCZ), voriconazole (Voriconazole, VCZ), itraconazole (Itraconazole, ICZ), amphotericin B (Amphotericin B, AMB) etc., the defects such as but these compounds still exist, and above-mentioned toxic and side effects is large, narrow antimicrobial spectrum, easily generation drug resistance, the dosage such as played needed for drug effect is comparatively large, thus can produce larger toxic and side effects to human body.。
Summary of the invention
The object of the invention is for deficiency of the prior art, a kind of application of throat azoles miazines compound is provided.
For achieving the above object, the technical scheme that the present invention takes is: a kind of throat azoles miazines compound is preparing the application in infection by Cryptococcus neoformans disease medicament, described throat azoles miazines compound is N3-(4-fluorophenyl)-1H-pyrazolo [3,4-D] pyrimidine-3,4-diamidogen.
The invention has the advantages that: compound of the present invention has good antifungal activity to various superficial part and deep fungal, compared with the antifungal drug of existing clinical practice, to there is the advantages such as efficient, hypotoxicity, anti-fungus spectra are wide, can be used for preparing antifungal drug.
Detailed description of the invention
Below detailed description of the invention provided by the invention is elaborated.
Embodiment 1
Below detailed description of the invention provided by the invention is elaborated.
(1) experimental technique: adopt conventional antibacterial experiment in vitro method (referring to: Antimicrob Agents Chemother 1995,39 (5): 1169)
1. materials and methods
(1) testing compound of the present invention: N3-(4-fluorophenyl)-1H-pyrazolo [3,4-D] pyrimidine-3,4-diamidogen
The experiment of particular compound:
Buy the Tocris Bioscience(U.S., Ellisville) ready-made compound (Cat. No. 2731) carries out cytologic experiment, and specifying information is as follows:
CGP57380，CAS?number：522629-08-9
Molecular weight: 244.23
Chemical name: N3-(4-fluorophenyl)-1H-pyrazolo [3,4-D] pyrimidine-3,4-diamidogen (N3-(4-Fluorophenyl)-1H-pyrazolo-[3,4-d] pyrimidine-3,4-diamine)
Molecular formula: C
11h
9fN
6.
Experimental strain is as follows:
This experiment has selected following 8 kinds of common human body cause illness's standard fungal bacterial strains as screening object:
Table 1 antifungal activity in-vitro screening strain subject
| Strain name | Species | Strain number |
| Candida albicans bacterium | Candida albicans | Y0109 |
| Candida albicans bacterium | Candida albicans | SC5314 |
| Candida parapsilosis bacterium | Candida parapsilosis | ATCC 22019 |
| Candida glabrata | Candida glabrata | 537 |
| Neogenesis cryptococcus | cryptococcus neoformans | 32609 |
| Gypsum Fibrosum shape sporidiole bacteria | Microsporum gypseum | Cmccfmza |
| Trichophyton | Trichophyton rubrum | Cmccftla |
| Aspergillus fumigatus | Aspergillus fumigatus | 07544 |
(2) test method
Bacteria suspension is prepared: above-mentioned fungus is cultivated 16 hours through YEPD fluid medium 35 DEG C, twice activation, with blood cell counting plate counting, with RPM1640 fluid medium adjustment bacteria concentration to 1 × 10
4~ 1 × 10
5individual/mL.
Drug solution preparing: get testing compound of the present invention and be dissolved in dimethyl sulfoxine, is made into the medicament storage liquid of 8.0mg/mL, tests front RPM1640 and is diluted to 640 μ g/mL.
Inoculation: get drug sensitive plate, adding RPMI RPMI-1640 200 μ l in often arranging No. 1 hole, making blank; No. 12 holes add bacterium liquid 200 μ l to be measured, make negative control; Drug sensitive plate is often arranged 2 ~ No. 11 holes and is added bacterium liquid 180 μ l respectively, fully mixes, and make the final drug level in each hole be respectively 64,32,16,8,4,2,1,0.5,0.25 and 0.125 μ g/ml, in each hole, DMSO content is all lower than 1%; No. 12 hole not drug containing, make positive control.Control drug is fluconazol (FCZ), itraconazole (ICZ), voriconazole (VCZ), ketoconazole (KCZ), terbinafine (TBR), amphotericin B (AMB).
Cultivate and detect: set Positive control wells optical density value (OD value) as 100%, with optical density value than Positive control wells lower than 80% lowest concentration of drug for minimal inhibitory concentration value (MIC
80).
(2) experimental result
Antibacterial experiment in vitro the results are shown in Table 2.
Table 2 the compounds of this invention is to common causative fungus external activity (MIC, μ g/ml)
| Compound | Y0109 | SC5314 | Nearly flat 22019 | Newly hidden 32609 | Smooth 537 | Cigarette song 07544 | Red hair Cmccftla | The little Cmccfmza of stone |
| c1 | 8 | 8 | 2 | 1 | 1 | >64 | >64 | >64 |
| ICZ | 8 | 4 | 8 | 4 | 8 | 8 | 2 | 2 |
| TRB | 64 | 32 | 1 | 1 | 4 | 0.5 | 0.125 | 0.0625 |
| KCZ | 0.25 | 0.25 | 0.5 | 0.125 | 0.5 | 8 | 1 | 1 |
| VCZ | 0.03125 | 0.0625 | 0.03125 | 0.0156 | 0.03125 | 0.25 | 0.03125 | 0.125 |
| AMB | 2 | 1 | 2 | 1 | 2 | 2 | 1 | 0.125 |
| FCZ | 0.5 | 0.5 | 1 | 1 | 1 | >64 | 8 | 8 |
Note: KCZ. ketoconazole, FCZ. fluconazol, VCZ. Wo Likang azoles, ICZ. itraconazole, TRB. terbinafine, AMB amphotericin
Above-mentioned experimental result shows that compound of the present invention has good antifungal activity, and the vitro inhibition activity of compound to selected fungus is all far better than fluconazol, illustrates that the compounds of this invention can be used for preparing the medicine of anti-fungal infection.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the prerequisite not departing from the inventive method; can also make some improvement and supplement, these improve and supplement and also should be considered as protection scope of the present invention.
Claims (1)
1. throat azoles miazines compound is preparing the application in infection by Cryptococcus neoformans disease medicament, and described throat azoles miazines compound is N3-(4-fluorophenyl)-1H-pyrazolo [3,4-D] pyrimidine-3,4-diamidogen.
Priority Applications (1)
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|---|---|---|---|
| CN201310332525.0A CN103405439B (en) | 2013-08-02 | 2013-08-02 | Application of pyrimidine compound to preparing antifungal medicines |
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|---|---|---|---|
| CN201310332525.0A CN103405439B (en) | 2013-08-02 | 2013-08-02 | Application of pyrimidine compound to preparing antifungal medicines |
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|---|---|
| CN103405439A CN103405439A (en) | 2013-11-27 |
| CN103405439B true CN103405439B (en) | 2014-12-31 |
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| CN201310332525.0A Expired - Fee Related CN103405439B (en) | 2013-08-02 | 2013-08-02 | Application of pyrimidine compound to preparing antifungal medicines |
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Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1348707B1 (en) * | 2002-03-28 | 2010-08-25 | Ustav Experimentalni Botaniky AV CR, v.v.i. (Institute of Experimental Botany Academy of Sciences of the Czech Republic, PRO) | Pyrazolo[4,3-d]pyrimidines, processes for their preparation and methods for therapy |
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2013
- 2013-08-02 CN CN201310332525.0A patent/CN103405439B/en not_active Expired - Fee Related
Non-Patent Citations (3)
| Title |
|---|
| Negative Regulation of Protein Translation by Mitogen-Activated Protein Kinase-Interacting Kinases 1 and 2;URSULA KNAUF et al;《MOLECULAR AND CELLULAR BIOLOGY》;20010831;第21卷(第16期);第5500-5511页 * |
| 第2页最后1段 * |
| 第46页2段. * |
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