CN105669573A - Isopropyl amino azole antifungal compound, and preparation method and application thereof - Google Patents
Isopropyl amino azole antifungal compound, and preparation method and application thereof Download PDFInfo
- Publication number
- CN105669573A CN105669573A CN201610007802.4A CN201610007802A CN105669573A CN 105669573 A CN105669573 A CN 105669573A CN 201610007802 A CN201610007802 A CN 201610007802A CN 105669573 A CN105669573 A CN 105669573A
- Authority
- CN
- China
- Prior art keywords
- compound
- monosubstituted
- para
- preparation
- isopropylamine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 0 CC*C*(C)CC=CCC(C*(C)C(C)C)(C(C=CCC1CN)=C1N)O Chemical compound CC*C*(C)CC=CCC(C*(C)C(C)C)(C(C=CCC1CN)=C1N)O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of medicine, and in particular, relates to a new azole alcohol antifungal compound having the following chemical structural general formula defined in the specification, and a preparation method and an application thereof, wherein R is selected from the group consisting of halogen, alkyl, nitro and cyano group. The compound has good antifungal activity on various superficial and deep fungi, has the advantages of high efficiency, low toxicity, wide antifungal spectra and the like compared with current clinical applied antifungal drugs, and can be used for preparation of antifungal drugs.
Description
Technical field
The present invention relates to pharmaceutical technology field, specifically, be that a kind of isopropylamine is for azole antifungal compound and preparation method thereof and the application in antifungal field.
Background technology
In recent years, the sickness rate of deep fungal infection rises year by year, serious threat human health. Triazole type medicine is the most commonly used class novel antifungal drugs of clinical practice, and it represents medicine fluconazol, ketoconazole and voriconazole has become a line medication for the treatment of deep fungal infection. But also used by this class antifungal drug clinically long-term a large amount of so that the drug resistance problems of fungus becomes increasingly conspicuous, clinically in the urgent need to wide spectrum, efficiently, the novel antifungal drugs of low toxicity. Therefore, design synthesizing new antifungal drug becomes the focus in research, the synthesis of the derivant being especially lead compound with fluconazol.
Chinese patent 2014102173842 discloses a kind of sulfur-bearing azole antifungal compound, and this compounds has triazole structure too. Those skilled in the art know, and on the right side of 3 C atoms of triazole class compounds, the pharmacokinetic property of the physicochemical property of whole molecule, molecule is all had considerable influence by linking group, and the linking group of different structure is likely to be of different even contrary pharmacologically active. And about the 1-(1H-1 of the present invention, 2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (substituted benzyl dithio carbomethoxy)]-2-alcohol compound and antifungal activity thereof, yet there are no report.
Summary of the invention
It is an object of the invention to for deficiency of the prior art, it is provided that a kind of isopropylamine is for azole antifungal compound.
Another purpose of the present invention is to provide the isopropylamine described above preparation method for azole antifungal compound.
Another the purpose of the present invention is to provide the isopropylamine described above purposes for azole antifungal compound.
For achieving the above object, the present invention adopts the technical scheme that:
A kind of isopropylamine is for azole antifungal compound, and described isopropylamine for azole antifungal compound general structure is:
Wherein R is selected from:
I. halogen, described halogen be selected from F, Cl or Br, can be located at the neighbour of aromatic ring, or para-position; Wherein substituent group F and Br is monosubstituted, and substituent group Cl can be monosubstituted or polysubstituted;
Ii. alkyl, described alkyl is the alkyl of 1-4 carbon atom, substituent group can be located at aromatic ring neighbour, or para-position, for monosubstituted;
Iii. nitro, described nitro be positioned at aromatic ring neighbour, or para-position, for monosubstituted; Or
Iv. cyano group, described cyano group be positioned at aromatic ring neighbour, or para-position, for monosubstituted.
Preferably, described substituent R is selected from:
Halogen, described halogen be selected from F, Cl or Br, can be located at the neighbour of aromatic ring, or para-position; Wherein substituent group F and Br is monosubstituted, and substituent group Cl can be monosubstituted or polysubstituted.
Preferably, described substituent R is selected from:
Alkyl, described alkyl is the alkyl of 1-4 carbon atom, substituent group can be located at aromatic ring neighbour, or para-position, for monosubstituted.
Preferably, described substituent R is selected from:
Nitro, described nitro be positioned at aromatic ring neighbour, or para-position, for monosubstituted.
Preferably, described substituent R is selected from:
Cyano group, described cyano group be positioned at aromatic ring neighbour, or para-position, for monosubstituted.
More preferably, described substituent R is selected from:
For realizing above-mentioned second purpose, the present invention adopts the technical scheme that:
Isopropylamine described above, for the preparation method of azole antifungal compound, comprises the steps:
A) compound 1 and chloracetyl chloride reacting generating compound 2;
B) compound 2 and triazole reacting generating compound 3;
C) compound 3 generates compound 4 with iodate trimethyl oxygen reaction of Salmon-Saxl;
D) compound 4 and 2-aminopropane. reacting generating compound 5;
E) bromobenzyl and CS are replaced2Ice bath reacts, and adds compound 5 and reacts, obtains target compound 6;
Described compound 1-6 structure and reaction scheme are as follows:
Preferably, the specifically comprising the following steps that of described preparation method
A) compound 1 and chloracetyl chloride occur friedel-crafts reaction to generate compound 2 under aluminum trichloride (anhydrous) existent condition;
B) compound 2 and triazole, 3-ethyl benzyl ammonium chloride (TEBA) and potassium carbonate are at CH2Cl2Middle 0-5 DEG C is reacted 5 hours, then room temperature reaction 12 hours, and raw compounds 3;
C) compound 3 and iodate trimethyl oxygen sulfur, trimethyl cetyl ammonium bromide, reacting generating compound 4 in toluene and sodium hydroxide;
D) compound 4 generates compound 5 with 2-aminopropane. reacting by heating in ethanol;
E) bromobenzyl and CS are replaced2Ice bath reacts 10 minutes, adds compound 5 room temperature reaction, obtains target compound 6.
More preferably, the preparation method of described step e) is as follows:
E) replacement bromobenzyl 0.6mmol and Carbon bisulfide 91.37mg (1.2mmol) is added at 20ml eggplant type bottle, ice bath stirs 10 minutes, it is subsequently adding 1-(1H-1,2,4-triazol-1-yls)-2-(2,4 difluorophenyl)-3-isopropyl-2-alcohol 88.8mg (0.3mmol), stirring, recovering to room temperature to continue reaction, after 9 hours, reaction terminates, and column chromatography purification obtains target compound.
For realizing above-mentioned 3rd purpose, the present invention adopts the technical scheme that:
As above arbitrary described isopropylamine is for azole antifungal compound application in preparing antifungal drug.
Preferably, described fungus is candida albicans bacterium, Candida parapsilosis bacterium, Candida glabrata, neogenesis cryptococcus, Sabouraudites lanosus, trichophyton or Aspergillus fumigatus.
The present invention also provides for a kind of antifungal medicine composition, comprises one or more as above arbitrary described compounds of therapeutically effective amount, and containing customary pharmaceutical excipients, carrier or diluent.
The present invention also provides for isopropylamine described above for azole antifungal compound pharmaceutically acceptable salt. Described pharmaceutically acceptable salt is acylate or inorganic acid salt; Wherein mineral acid includes: hydrochloric acid, sulphuric acid, phosphoric acid, diphosphonic acid, hydrobromic acid or nitric acid; Organic acid includes: acetic acid, maleic acid, fumaric acid, tartaric acid, succinic acid, lactic acid, p-methyl benzenesulfonic acid, salicylic acid or oxalic acid. The preparation method of salt can be prepared with this area conventional means, as prepared sodium salt with the alkali such as NaOH reaction of the compound containing phenolic hydroxyl group Yu equimolar amounts;Phosphate etc. is prepared with the compound containing phenolic hydroxyl group and phosphatase reaction.
The present invention also provides for isopropylamine described above for the raceme of azole antifungal compound, R type or S type isomer.
The invention has the advantages that:
By pharmacological evaluation, the compound of the present invention proves that deep fungal is had good anti-mycotic efficiency, compared with the antifungal drug of existing clinical practice, have the advantages such as efficient, hypotoxicity, antifungal spectrum width, can be used for preparing new antifungal drug.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is expanded on further. Should be understood that these embodiments are merely to illustrate the present invention rather than restriction the scope of the present invention. In addition, it is to be understood that after having read present disclosure, the present invention can be made various changes or modifications by those skilled in the art, these equivalent form of values fall within the application appended claims limited range equally.
The preparation of embodiment 1 the compounds of this invention
The compounds of this invention to prepare reaction scheme as follows:
The first step, synthetic intermediate 4:
Second step, synthetic intermediate 5:
3rd step, synthesising target compound 6:
Specifically, preparing of the particular compound related in above-mentioned preparation method is as follows:
(1) chloro-2 ', the 4 '-difluoro acetophenone of 2-(intermediate 2) is prepared
M-difluorobenzene and chloracetyl chloride occur friedel-crafts reaction to generate chloro-2 ', the 4 ' difluoro acetophenones (2) of 2-under aluminum trichloride (anhydrous) existent condition.
(2) 2-(1H-1,2,4-triazol-1-yl)-2 ', 4 '-difluoro acetophenone (intermediate 3) are prepared
Chloro-2 ', the 4 '-difluoro acetophenone of 2-and triazole, 3-ethyl benzyl ammonium chloride (TEBA) and potassium carbonate are at CH2Cl2Middle 0-5 DEG C is reacted 5 hours, then room temperature reaction 12 hours, generates 2-(1H-1,2,4-triazol-1-yl)-2 ', 4 '-difluoro acetophenone (3).
(3) 1-[2-(2,4 difluorobenzene base)-2,3-glycidyl]-1H-1,2,4-triazolium methanesulfonat (intermediate 4) is prepared
2-(1H-1,2,4-triazol-1-yl)-2 ', 4 '-difluoro acetophenone and iodate trimethyl oxygen sulfur, trimethyl cetyl ammonium bromide, in toluene and sodium hydroxide, reaction generates 1-[2-(2,4-difluorophenyl)-2,3-glycidyl]-1H-1,2,4-triazolium methanesulfonat (4).
(4) 1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-(N-isopropyl) amido-2-alcohol (intermediate 5) is prepared
Intermediate 4 and 2-aminopropane. reacting by heating in ethanol, generates 1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-(N-isopropyl) amido-2-alcohol (5).
(5) target compound is prepared
Replace bromobenzyl and CS2Ice bath reacts 10 minutes, adds intermediate 5 room temperature reaction, generates target compound.
Specifically, target compound 1-15 preparation method is as follows:
1, target compound 1:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (benzyl dithio carbomethoxy)]-2-alcohol is prepared; With bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
2, target compound 2:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (3-luorobenzyl dithio carbomethoxy)]-2-alcohol is prepared;
A) intermediate 2-5 is prepared with reference to said method;
B) 3-fluorine bromobenzyl 113.41mg (0.6mmol) and Carbon bisulfide 91.37mg (1.2mmol) is added at 20ml eggplant type bottle, ice bath stirs 10 minutes, it is subsequently adding 1-(1H-1, 2, 4-triazol-1-yl)-2-(2, 4 difluorophenyls)-3-isopropyl-2-alcohol 88.8mg (0.3mmol), stirring, recover to room temperature to continue reaction, after 9 hours, reaction terminates, column chromatography purification obtains 1-(1H-1, 2, 4-triazol-1-yl)-2-(2, 4 difluorophenyls)-3-[N-(3-luorobenzyl dithio carbomethoxy)-isopropyl]-2-alcohol 54mg, productivity 50.6%,
3, target compound 3:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (4-luorobenzyl dithio carbomethoxy)]-2-alcohol is prepared; With 4-fluorine bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
4, target compound 4:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (2-chlorobenzyl dithio carbomethoxy)]-2-alcohol is prepared; With 2-chlorine bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
5, target compound 5:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (3-chlorobenzyl dithio carbomethoxy)]-2-alcohol is prepared; With 3-chlorine bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
6, target compound 6:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (4-chlorobenzyl dithio carbomethoxy)]-2-alcohol is prepared; With 4-chlorine bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
7, target compound 7:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (2-bromobenzyl dithio carbomethoxy)]-2-alcohol is prepared; With 2-bromine bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
8, target compound 8:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (3-bromobenzyl dithio carbomethoxy)]-2-alcohol is prepared; With 3-bromine bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
9, target compound 9:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (4-bromobenzyl dithio carbomethoxy)]-2-alcohol is prepared; With 4-bromine bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
10, target compound 10:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (3-methyl-benzyl dithio carbomethoxy)]-2-alcohol is prepared; With 3-methyl bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
11, target compound 11:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (3-nitrobenzyl dithio carbomethoxy)]-2-alcohol is prepared; With 3-nitro bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
12, target compound 12:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (3-cyanobenzyls dithio carbomethoxy)]-2-alcohol is prepared; With 3-cyano-benzyl bromide for raw material, concrete preparation method is with the preparation of compound 2.
13, target compound 13:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (4-cyanobenzyls dithio carbomethoxy)]-2-alcohol is prepared; With 4-cyano-benzyl bromide for raw material, concrete preparation method is with the preparation of compound 2.
14, target compound 14:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (2,6-dichloro benzyl dithio carbomethoxy)]-2-alcohol is prepared; With 2,6-dichloro bromobenzyls for raw material, concrete preparation method is with the preparation of compound 2.
15, target compound 15:1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (4-t-butylbenzyl dithio carbomethoxy)]-2-alcohol is prepared; With 4-tert-butyl group bromobenzyl for raw material, concrete preparation method is with the preparation of compound 2.
It should be noted that when preparing all the other target compounds, adopt the replacement bromobenzyl of corresponding R group as raw material, method is ibid. In the embodiment of the present invention, agents useful for same is commercially available analytical pure. The chemical constitution of compound prepared above, productivity, nucleus magnetic hydrogen spectrum data are as follows:
The chemical constitution of table 1 part of compounds, productivity and molecular formula
The enforcement of the present invention is not limited to above example, and all the other target compounds all can be synthesized by above method.
The pharmacological evaluation of embodiment 2 the compounds of this invention
The present invention synthesizes 1-(1H-1,2,4-triazol-1-yl)-2-(2,4 difluorophenyl)-3-[N-isopropyl amido (substituted benzyl dithio carbomethoxy)]-2-alcohol compound has antifungic action, and its pharmacological evaluation is as follows:
(1) experimental technique: adopt conventional antibacterial experiment in vitro method (referring to: AntimicrobAgentsChemother1995,39 (5): 1169)
1. materials and methods
(1) experimental strain
This experiment has selected following human body cause illness's standard fungal bacterial strain 8 kinds common as screening object:
Table 2 antifungal activity in-vitro screening strain subject
(2) test method
Bacteria suspension is prepared: above-mentioned fungus is cultivated 16 hours through YEPD fluid medium 35 DEG C, twice activation, counts with blood cell counting plate, adjusts bacteria concentration to 1 × 10 with RPM1640 fluid medium4～1 × 105Individual/mL.
Drug solution preparing: take testing compound of the present invention and be dissolved in dimethyl sulfoxide, the medicine being made into 8.0mg/mL stores liquid, tests front RPM1640 and is diluted to 640 μ g/mL.
Inoculation: take drug sensitive plate, add RPMI1640 culture fluid 200 μ l in often arranging No. 1 hole, make blank; No. 12 holes add bacterium solution 200 μ l to be measured, make negative control; Drug sensitive plate is often arranged 2-11 hole and is added bacterium solution 180 μ l respectively, fully mixes, and makes final drug level respectively 64,32,16,8,4,2,1,0.5, the 0.25 and 0.125 μ g/ml in each hole, and in each hole, DMSO content is below 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 detection: set Positive control wells optical density value (OD value) as 100%, with optical density value than the Positive control wells lowest concentration of drug lower than 80% for minimal inhibitory concentration value (MIC80)。
(2) experimental result
Antibacterial experiment in vitro result is in Table 3.
Table 3 part preferred compound is to common causative fungus external activity (MIC80,μg/ml)
Note: KCZ. ketoconazole, FCZ. fluconazol, VCZ. Wo Likang azoles, ICZ. itraconazole, TRB. terbinafine, AMB amphotericin
Above-mentioned test result indicate that compound of the present invention has good antifungal activity, the vitro inhibition activity of selected fungus all much stronger than fluconazol, is illustrated that the compounds of this invention can be used for preparing the medicine of anti-fungal infection by multiple compounds.
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 premise without departing from the inventive method; can also making some improvement and supplement, these improve and supplement and also should be regarded as protection scope of the present invention.
Claims (10)
1. an isopropylamine is for azole antifungal compound, it is characterised in that described isopropylamine for azole antifungal compound general structure is:
Wherein R is selected from:
I. halogen, described halogen is selected from F, Cl or Br, is positioned at the ortho position of aromatic ring, a position or para-position; Wherein substituent group F and Br is monosubstituted, and substituent group Cl can be monosubstituted or polysubstituted;
Ii. alkyl, described alkyl is the alkyl of 1-4 carbon atom, is positioned at the ortho position of aromatic ring, a position or para-position, for monosubstituted;
Iii. nitro, described nitro is positioned at the ortho position of aromatic ring, a position or para-position, for monosubstituted; Or
Iv. cyano group, described cyano group is positioned at the ortho position of aromatic ring, a position or para-position, for monosubstituted.
2. isopropylamine according to claim 1 is for azole antifungal compound, it is characterised in that described substituent R is selected from:
Halogen, described halogen is selected from F, Cl or Br, is positioned at the ortho position of aromatic ring, a position or para-position; Wherein substituent group F and Br is monosubstituted, and substituent group Cl can be monosubstituted or polysubstituted.
3. isopropylamine according to claim 1 is for azole antifungal compound, it is characterised in that described substituent R is selected from:
Alkyl, described alkyl is the alkyl of 1-4 carbon atom, is positioned at the ortho position of aromatic ring, a position or para-position, for monosubstituted.
4. isopropylamine according to claim 1 is for azole antifungal compound, it is characterised in that described substituent R is selected from:
Nitro, described nitro is positioned at the ortho position of aromatic ring, a position or para-position, for monosubstituted; Or
Cyano group, described cyano group is positioned at the ortho position of aromatic ring, a position or para-position, for monosubstituted.
5. isopropylamine according to claim 1 is for azole antifungal compound, it is characterised in that described substituent R is selected from:
。
6. the arbitrary described isopropylamine of claim 1-5 is for the preparation method of azole antifungal compound, it is characterised in that comprise the steps:
A) compound 1 and chloracetyl chloride reacting generating compound 2;
B) compound 2 and triazole reacting generating compound 3;
C) compound 3 generates compound 4 with iodate trimethyl oxygen reaction of Salmon-Saxl;
D) compound 4 and 2-aminopropane. reacting generating compound 5;
E) bromobenzyl and CS are replaced2Ice bath reacts, and adds compound 5 and reacts, obtains target compound 6;
Described compound 1-6 structure is as follows:
7. preparation method according to claim 6, it is characterised in that specifically comprising the following steps that of described preparation method
A) compound 1 and chloracetyl chloride occur friedel-crafts reaction to generate compound 2 under aluminum trichloride (anhydrous) existent condition;
B) compound 2 and triazole, 3-ethyl benzyl ammonium chloride (TEBA) and potassium carbonate are at CH2Cl2Middle 0-5 DEG C is reacted 5 hours, then room temperature reaction 12 hours, and raw compounds 3;
C) compound 3 and iodate trimethyl oxygen sulfur, trimethyl cetyl ammonium bromide, reacting generating compound 4 in toluene and sodium hydroxide;
D) compound 4 generates compound 5 with 2-aminopropane. reacting by heating in ethanol;
E) bromobenzyl and CS are replaced2Ice bath reacts 10 minutes, adds compound 5 room temperature reaction, obtains target compound 6.
8. the arbitrary described isopropylamine of claim 1-5 is for azole antifungal compound application in preparing antifungal drug.
9. application according to claim 8, it is characterised in that described fungus is candida albicans bacterium, Candida parapsilosis bacterium, Candida glabrata, neogenesis cryptococcus, Sabouraudites lanosus, trichophyton or Aspergillus fumigatus.
10. an antifungal medicine composition, it is characterised in that comprise the arbitrary described compound of one or more claim 1-5 of therapeutically effective amount, and containing customary pharmaceutical excipients, carrier or diluent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610007802.4A CN105669573B (en) | 2016-01-05 | 2016-01-05 | A kind of isopropylamine is for azole antifungal compound and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610007802.4A CN105669573B (en) | 2016-01-05 | 2016-01-05 | A kind of isopropylamine is for azole antifungal compound and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105669573A true CN105669573A (en) | 2016-06-15 |
| CN105669573B CN105669573B (en) | 2018-02-23 |
Family
ID=56299115
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610007802.4A Expired - Fee Related CN105669573B (en) | 2016-01-05 | 2016-01-05 | A kind of isopropylamine is for azole antifungal compound and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105669573B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010014742A1 (en) * | 1999-02-19 | 2001-08-16 | Jerzy Golik | Water-soluble prodrugs of azole compounds |
| CN101357906A (en) * | 2008-09-09 | 2009-02-04 | 中国人民解放军第二军医大学 | Novel triazolols antifungal compound, preparation method and application thereof |
| CN101602738A (en) * | 2009-07-20 | 2009-12-16 | 中国人民解放军第二军医大学 | Novel azole antifungal compound and preparation method thereof |
| CN104003947A (en) * | 2014-05-22 | 2014-08-27 | 中国人民解放军第二军医大学 | Sulfur/nitrogen-containing azole antifungal compound as well as preparation method and application of sulfur-containing azoles antifungal compound |
-
2016
- 2016-01-05 CN CN201610007802.4A patent/CN105669573B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010014742A1 (en) * | 1999-02-19 | 2001-08-16 | Jerzy Golik | Water-soluble prodrugs of azole compounds |
| CN101357906A (en) * | 2008-09-09 | 2009-02-04 | 中国人民解放军第二军医大学 | Novel triazolols antifungal compound, preparation method and application thereof |
| CN101602738A (en) * | 2009-07-20 | 2009-12-16 | 中国人民解放军第二军医大学 | Novel azole antifungal compound and preparation method thereof |
| CN104003947A (en) * | 2014-05-22 | 2014-08-27 | 中国人民解放军第二军医大学 | Sulfur/nitrogen-containing azole antifungal compound as well as preparation method and application of sulfur-containing azoles antifungal compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105669573B (en) | 2018-02-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5620994A (en) | Azolylamine derivative | |
| CN101602738B (en) | Novel azole antifungal compound and preparation method thereof | |
| CN101357906A (en) | Novel triazolols antifungal compound, preparation method and application thereof | |
| Xu et al. | Lead optimization generates selenium-containing miconazole CYP51 inhibitors with improved pharmacological profile for the treatment of fungal infections | |
| CN104003947B (en) | A kind of sulfur-bearing azole antifungal compound and its production and use | |
| CN101402613B (en) | Substituted phenoxy oxygen alkylamine triazole alcohol antimycotic compounds and method of preparing the same | |
| CN102503901B (en) | Zole antifungal compounds, and preparation method and application thereof | |
| CN103265538A (en) | Azole antifungal compound and preparation method and application thereof | |
| CN101768126B (en) | Novel triazole antifungal compound and salt thereof | |
| CN101781263B (en) | Nitrogen methyl side chain-substituted triadimenol antifungal compound and preparation method thereof | |
| CN105669573A (en) | Isopropyl amino azole antifungal compound, and preparation method and application thereof | |
| CN103275024B (en) | Azole antifungal compound and its preparation method and application | |
| CN103951625B (en) | A kind of 1,2,3-triazoles class antifungal compound containing piperazinyl and its preparation method and application | |
| Saleh et al. | Novel 6‐hydroxyquinolinone derivatives: Design, synthesis, antimicrobial evaluation, in silico study and toxicity profiling | |
| CN105503753B (en) | A kind of allyl amine is for azole antifungal compound and its preparation method and application | |
| CN104003948B (en) | Azole compounds and its preparation method and application | |
| CN102796080B (en) | A kind of novel azole antifungal compound and its preparation method and application | |
| CN105524004A (en) | Propylaminoazole antifungal compounds, and preparation method and application thereof | |
| CN103387548B (en) | 1,2,3-triazole antifungal compounds, and preparation method and application thereof | |
| CN105669572A (en) | Piperazinyl amine azole antifungal compound, and preparation method and application thereof | |
| CN103214457B (en) | A kind of azole antifungal compound and its preparation method and application | |
| CN103450162B (en) | Triazole alcohol compound containing benzamide structure and preparation method and application of triazole alcohol compound | |
| CN103951626B (en) | 1,2,3-triazoles class antifungal compound that a kind of benzyl replaces and its preparation method and application | |
| US9758490B2 (en) | Antifungal compounds of (arylalkyl) azole derivatives in the structure of oxime ester | |
| US9693974B2 (en) | Antibacterial and antifungal biphenylyl compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180223 Termination date: 20210105 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |