CN102153548A - Analogue nucleoside derivative containing thiazolidone (thiazinidone) ring, preparation method and application thereof to medicinal preparations - Google Patents
Analogue nucleoside derivative containing thiazolidone (thiazinidone) ring, preparation method and application thereof to medicinal preparations Download PDFInfo
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Abstract
The invention discloses an analogue nucleoside derivative containing a thiazolidone (thiazinidone) ring, a preparation method and application thereof to medicinal preparations. The preparation method comprises the following steps of: a, dissolving fatty amine or aromatic amine (1) and furfural (2) which serve as initial raw materials in absolute methanol solvent with stirring according to a molar ratio of 1.2:1; and b, performing microwave radiation or stirring at the room temperature, adding mercaptoacetic acid or mercaptopropionic acid according to a molar ratio of 1:2 and reacting, and regulating the pH value to be between 6.5 and 7.5 to obtain a compound shown as a chemical general formula (I).
Description
Technical field
The present invention relates to class nucleoside derivates and synthetic method thereof and its application in pharmaceutical preparation, specifically relate to contain class nucleoside derivates and synthetic method and its application in pharmaceutical preparation of thiazole (piperazine) alkane ketone ring.
Background technology
Immunity is the crucial physiological function of body.Normal immunologic function is the assurance of body health, in case immune dysfunction will cause the reaction of disease and immunopathogenesis.The generation of many clinical diseases such as malignant tumour, virus disease and autoimmune disease etc., development all have close getting in touch with the functional disorder and the immunodeficiency of body immune system.Immunomodulator by and the various lymphocytes of immunity system between interaction or immune molecule intrinsic network activation, adjust body's immunity, correct immunologic derangement, be the medicine that a class can strengthen non-specificly or suppress body's immunity.At present, clinical widely used immunomodulator is mainly biological products and part microbial metabolism class medicine, as Zadaxin, Interferon, rabbit, interleukin, bacille Calmette-Guerin vaccine, ciclosporin A, mycophenlate mofetil, rapamycin etc., because these medicines exist toxic side effect big, water-soluble and poor stability, purity and tire shortcoming such as low, therefore, demand developing the novel immunomodulator of high-efficiency low-toxicity urgently.
Chemosynthesis small molecules immunomodulator, because the needs of its good chemistry and zymetology stability, the multiple formulation of adaptation and route of administration, and cost is lower, purity is high, can reduce toxic side effect when raising is tired, avoid the untoward reaction of hormone medicine and biogenetic derivation immunomodulator, caused that people pay close attention to widely.At present more existing small molecules immunomodulators are applied to clinical, as pidotimod, CGP52608 and Nucleotide, glucosides (peptide) analogue etc.Yet characteristics such as that immunomodulatory has is various, complicated and target spot is uncertain, therefore, existing small molecules immunomodulator can not satisfy clinical immunoregulatory research and application far away.
Summary of the invention
Purpose of the present invention is exactly that a kind of new small molecules immunomodulator will be provided, be a kind of class nucleoside derivates that contains thiazole (piperazine) alkane ketone ring, a kind of synthetic method and the application of this compounds in preparation immunoregulation druge preparation of this compounds are provided simultaneously.
The object of the present invention is achieved like this:
The invention provides a kind of class nucleoside derivates that contains thiazole (piperazine) alkane ketone ring,
Its chemical general formula is shown in (I):
Wherein k is 1 or 2; M is 0 or 1; X is Sauerstoffatom or amino, R
1For hydrogen atom or hydroxyl or contain C
1-C
6The alkoxyl group of straight or branched; R
2For containing C
1-C
18Alkyl, the aryl of straight or branched.
Above-mentioned aryl can be selected phenyl for use, benzyl, the 4-p-methoxy-phenyl, the 4-aminomethyl phenyl, the 4-chloro-phenyl-, the 4-bromophenyl, the 4-iodophenyl, the 4-hydroxy phenyl, the 2-p-methoxy-phenyl, the 2-aminomethyl phenyl, the 2-chloro-phenyl-, the 2-bromophenyl, the 2-iodophenyl, the 2-hydroxy phenyl, the 3-p-methoxy-phenyl, the 3-aminomethyl phenyl, the 3-chloro-phenyl-, the 3-bromophenyl, the 3-iodophenyl, the 3-hydroxy phenyl, the 1-naphthyl, the 2-naphthyl, the 2-furyl, the 3-pyridyl, the 2-pyridyl, in the 4-pyridyl any one.
Aryl is defined as among the present invention:
Shown in (I) in the compound, preferred compound has following several compound at above-mentioned chemical general formula:
Wherein k is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be methyl;
Wherein k is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be butyl;
Wherein k is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be octyl group;
Wherein k is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be octadecyl;
Wherein k is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be phenyl.
Above-claimed cpd can be a pair of diastereomer (concrete structure is shown in (4), (5)) of following form.
Compound of the present invention shows through pharmacological evaluation, it has the effect of good promotion T cell-proliferation activity, thereby be active substance with compound of the present invention, with the carrier uniform mixing that allows on the pharmacology to use, can be prepared into the immunomodulator of various formulations according to the formulation method of routine.
As being active ingredient with the The compounds of this invention, be prepared into oral liquid with combination of components such as water, sucrose, Sionit, fructose; Be prepared into tablet or capsule with vehicle (lactose, glucose, sucrose, N.F,USP MANNITOL sugar), disintegrating agent (starch), lubricant (stearic acid, talcum powder), tackiness agent combination of components such as (gelatin, polyvinyl alcohol).
The compounds of this invention also can be prepared into injection liquid with the mixed carrier that physiological saline, glucose solution or salt solution and glucose are formed as active ingredient.
The present invention be used for when clinical can reference effective dose be 10～20mg/ people/day, every day 2～3 times.The doctor also can draft taking dose according to the patient individual difference.
Thus, the applicant has finished the purposes invention that this compound is used to prepare immunomodulator.
The preparation method who contains the class nucleoside derivates of thiazole (piperazine) alkane ketone ring provided by the present invention may further comprise the steps:
A, be starting raw material with aliphatic amide or aromatic amine (1), alditol (2), in the anhydrous methanol solvent, according to mol ratio 1.2: 1, stirring and dissolving;
B, microwave radiation or stirring at room according to mol ratio 1: 2, add the reaction of Thiovanic acid or thiohydracrylic acid (3), transfer pH6.5-7.5, obtain chemical general formula compound shown in (I);
Wherein k is 1 or 2; M is 0 or 1; X is Sauerstoffatom or amino, R
1For hydrogen atom or hydroxyl or contain C
1-C
6The alkoxyl group of straight or branched; R
2For containing C
1-C
18Alkyl, the aryl of straight or branched.
Reaction expression in the inventive method is as follows:
Description of drawings
Fig. 1 is the influence chart of The compounds of this invention to mouse T lymphocyte (ConA stimulation) propagation.
Wherein ordinate zou is represented T cell appreciation rate (%); X-coordinate is a test compounds; A is untreated splenocyte; B is the splenocyte that ConA stimulates;
The representation compound consumption is 100 μ m;
The representation compound consumption is 25 μ m; # represents P＜0.01, compares with A (untreated splenocyte);
*P＜0.05,
*P＜0.01,
* *Compare with B (splenocyte that ConA stimulates) P＜0.001.
Embodiment
To help the understanding of the present invention by following embodiment, but not limit content of the present invention in any form.
Embodiment 1
Synthetic compound (S)-2-((2S, 3S, 4S, 5R)-tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-methylthiazol alkane-4-ketone and compound (being called for short compound 4a) and (R)-2-((2S, 3S, 4S, 5R)-and tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-methylthiazol alkane-4-ketone (being called for short compound 5a).
Its chemical reaction flow process is as follows:
(1) is alditol in the above-mentioned reaction formula, (2a) is methylamine hydrochloride, and (3) are Thiovanic acid;
Concrete grammar is:
((2S, 3S, 4S, 5R)-3,4-dihydroxyl-5-(methylol) furans-2-formaldehyde) and methylamine hydrochloride (1.2equiv) are dissolved in the 3mL anhydrous methanol, and the room temperature nitrogen protection was stirred 60 minutes down to take by weighing 200mg (1.23mmol) alditol; Add Thiovanic acid (2.0equiv) subsequently, continued stirring at room 30 minutes, finish reaction, add Anhydrous potassium carbonate powder neutralization reaction liquid to pH=7, (methyl alcohol: column chromatography water=70: 30) obtains isomer 4a and 5a to the reverse phase silica gel post of last C18.
Starting raw material alditol in the present embodiment ((2S, 3S, 4S, 5R)-3, and 4-dihydroxyl-5-(methylol) furans-2-formaldehyde) can synthesize in accordance with the following methods:
Its chemical reaction flow process is as follows:
Concrete synthetic method may further comprise the steps:
D-glucosamine hydrochloride 6 (commercially available) 10.8g (50mmol) is used the 100ml water dissolution, in cryosel is bathed, add NaNO in batches
26.9g (100mmol), add H+ ion exchange resin 70g again, vigorous stirring is simultaneously kept 0～5 ℃ of the temperature of reaction system in batches, reinforced finishing, remove cryosel and bathe, vigorous stirring 1h under the room temperature (TLC monitoring reaction), reaction finishes, the elimination resin, filtrate is neutralized to neutrality with resin anion(R.A), elimination resin, concentrated filtrate, have in a large number and salt out, use the anhydrous methanol lysate, filtering salt, concentrated filtrate, with silicagel column separation and purification (second second: methyl alcohol=7: 1) get 6.5g yellow solid 1, yield is 85%, and fusing point is 31-32 ℃, [α]
25 D+ 31.7 (c 1.0, CH
3OH) (literature value: fusing point is 33 ℃, [α]
25 D+ 31.8 ° (c 1.0, CH
3OH), reference: Samantha, C., et al., Carbohydra.Res.1999,315,339-344.).
Synthetic compound (S)-2-((2S, 3S, 4S, 5R)-tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-butyl thiazolidin-4-one (be called for short compound 4b) and (R)-2-((2S, 3S, 4S, 5R)-and tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-butyl thiazolidin-4-one (being called for short compound 5b).
Its chemical reaction flow process is as follows:
(1) is alditol in the above-mentioned reaction formula, and (2b) n-Butyl Amine 99 is for (3) are Thiovanic acid;
Concrete grammar is:
((2S, 3S, 4S, 5R)-3,4-dihydroxyl-5-(methylol) furans-2-formaldehyde) and n-Butyl Amine 99 (1.2equiv) are dissolved in the 3mL anhydrous methanol, and the room temperature nitrogen protection was stirred 60 minutes down to take by weighing 200mg (1.23mmol) alditol; Add Thiovanic acid (2.0equiv) subsequently, continued stirring at room 30 minutes, finish reaction, add Anhydrous potassium carbonate powder neutralization reaction liquid to pH=7, (methyl alcohol: column chromatography water=72: 28) obtains isomer 4b and 5b to the reverse phase silica gel post of last C18.
Compound 5b: yellow syrup, yield 24.5%. δ
H(600MHz, CD
3OD): 0.98 (3H, J=7.2Hz, CH
3), 1.31-1.41 (2H, m, CH
2), 1.56-1.67 (2H, m, CH
2), 3.08-3.12 (1H, m, CH), 3.37 (1H, d, J=15.6Hz, H-5), 3.60 (1H, dd, J=12.0Hz, 4.8Hz, H-5), 3.72-3.77 (3H, m, CH, H-1 ', H-5 '), 3.89-3.93 (1H, m, H-4 '), 4.04-4.08 (2H, m, H-5 ', H-2 '), 4.17 (1H, d, J=6.6Hz, H-3 '), 4.91 (1H, s, H-2); δ
C(125MHz, CD
3OD): 12.7,19.6,28.8,32.5,42.2,61.4 (C-2), 64.1,76.0,77.9,80.6,83.8,172.9 (C-4); HRMS (ESI): Calcd for C
12H
21NO
5SNa (M+Na)
+, 314.1038, Found:314.1035
With reference to embodiment 1 and 2 described methods, be raw material with n-octyl amine (2c) and stearylamine (2d) respectively, can obtain the compound of following different optical isomer:
Compound 4c i.e. (S)-2-((2S, 3S, 4S, 5R)-tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-octyl group thiazolidin-4-one;
Compound 5c i.e. (R)-2-((2S, 3S, 4S, 5R)-tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-octyl group thiazolidin-4-one;
Compound 4d i.e. (S)-2-((2S, 3S, 4S, 5R)-tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-octadecyl thiazolidin-4-one;
Compound 5d i.e. (R)-2-((2S, 3S, 4S, 5R)-tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-octadecyl thiazolidin-4-one;
The particular chemical formula is as follows:
Compound 4c: colourless syrup, yield 24.0%. δ
H(600MHz, CD
3OD): 0.94 (3H, t, J=6.6Hz, CH
3), 1.33-1.36 (10H, m, 5CH
2), 1.61-1.69 (2H, m, CH
2), 3.34-3.35 (1H, m, CH); 3.49 (1H, d, J=15.6Hz, H-5), 3.65 (1H, dd, J=13.2Hz, 7.2Hz, H-5 '), 3.72-3.75 (2H, m, CH, H-5), 3.78-3.83 (1H, m, H-4 '), 3.98 (1H, q, J=5.4Hz, H-1 '), 4.03 (1H, t, J=4.8Hz, H-2 '), 4.15 (1H, q, J=4.8Hz, H-3 '), 5.01 (1H, dd, J=7.2Hz, 4.8Hz, H-2); δ
C(125MHz, CD
3OD); 13.2,22.4,26.5,29.0,29.1,31.4,31.7,44.3,61.9 (C-2), 62.2,77.5,78.9,85.4,86.6,172.6 (C-4); HRMS (ESI): Calcd for C
16H
29NO
5SNa (M+Na)
+, 370.1664, Found:370.1657.
Compound 5c: colourless syrup, yield 15.0%. δ
H(600MHz, CD
3OD): 0.92 (3H, t, J=6.6Hz, CH
3), 1.32-1.35 (10H, m, 5CH
2), 1.56-1.69 (2H, m, CH
2), 3.07-3.11 (1H, m, CH), 3.37 (1H, d, J=15.6Hz, H-5), 3.65 (1H, dd, J=12.0Hz, 4.8Hz, H-5 '), 3.67-3.77 (3H, m, CH, H-5, H-5 '), 3.89-3.92 (1H, m, H-4 '), 4.03-4.08 (2H, m, H-2 ', H-1 '), 4.16 (1H, d, J=6.6Hz, H-3 '), 4.90 (1H, s, H-2); δ
C(125MHz, CD
3OD): 13.0,22.3,26.4,26.6,28.9,28.9,31.5,32.4,42.45,61.5 (C-2), 64.1,76.1,77.8,80.6,83.8,172.9 (C-4); HRMS (ESI): Calcd for C
16H
29NO
5SNa (M+Na)
+, 370.1664, Found:370.1665.
Compound 4d: yellow solid, yield 13.8%. δ
H(600MHz, CD
3OD): 0.92 (3H, t, J=7.2Hz, CH
3), 1.31-1.37 (30H, m, 15CH
2), 1.61-1.70 (2H, m, CH
2), 3.34-3.39 (1H, m, CH), 3.47 (1H, d, J=15.6Hz, H-5), 3.64 (1H, dd, J=12.0Hz, 5.4Hz, H-5), 3.65-3.71 (1H, m, H-1 '), 3.73 (1H, t, J=3.6Hz, H-5 '), 3.77-3.82 (1H, m, CH), 3.96-3.98 (1H, m, H-4 '), 4.02 (1H, t, J=5.4Hz, H-5 '), 4.11 (1H, t, J=4.2Hz, H-2 '), 4.14 (1H, t, J=4.8Hz, H-3 '), 5.00 (1H, dd, J=7.2Hz, 1.8Hz, H-2); δ
C(125MHz, CD
3OD): 13.1,22.3,26.4,28.9,29.1,29.3,29.4,29.4,31.3,31.7,44.3,61.7 (C-2), 62.0,77.4,78.7,85.2,86.5,172.5 (C-4); HRMS (ESI): Calcd for C
26H
49NO
5SNa (M+Na)
+, 510.3229, Found:510.3232.
Compound 5d: white solid, yield 22.2%. δ
H(600MHz, CD
3OD): 0.93 (3H, t, J=6.6Hz, CH
3), 1.32-1.36 (30H, m, 15CH
2), 1.58-1.68 (2H, m, CH
2, H-5), 3.31-3.38 (2H, m, H-1 ', H-5), 3.59-3.82 (3H, m, CH, H-5 ', H-1), and 3.86-3.94 (1H, m, H-4 '), 4.06-4.09 (1H, m, H-2 '), 4.17-4.19 (1H, m, H-3 '), 4.91 (1H, s, H-2); δ
C(125MHz, CD
3OD): 13.1,22.2,26.6,28.9,29.1,29.4,29.7,31.3,32.5,42.3,61.5 (C-2), 64.1,76.0,78.8,83.6,84.5,172.5 (C-4); HRMS (ESI): Calcd for C
26H
49NO
5SNa (M+Na)
+, 510.3229, Found:510.3225.
Embodiment 3
Synthetic compound (S)-2-((2S, 3S, 4S, 5R)-tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-phenyl thiazole alkane-4-ketone (be called for short compound 4e) and (R)-2-((2S, 3S, 4S, 5R)-and tetrahydrochysene-3,4-dihydroxyl-5-(methylol) furans-2-yl)-3-phenyl thiazole alkane-4-ketone (being called for short compound 5e).
Its chemical reaction flow process is as follows:
Concrete grammar is:
((2S, 3S, 4S, 5R)-3,4-dihydroxyl-5-(methylol) furans-2-formaldehyde) and aniline 2e (1.2equiv) are dissolved in the 3mL anhydrous methanol, and the room temperature nitrogen protection was stirred 60 minutes down to take by weighing 200mg (1.23mmol) alditol 1; Add Thiovanic acid (2.0equiv) subsequently, continued stirring at room 30 minutes, finish reaction, add Anhydrous potassium carbonate powder neutralization reaction liquid to pH=7, (methyl alcohol: column chromatography water=70: 30) obtains isomer 4e and 5e to the reverse phase silica gel post of last C18.
Embodiment 4
Compound is to mouse T lymphocyte proliferation activity testing method: get the BALb/C mouse boosting cell, be made into 4.5 * 10 with the RPMI1640 substratum that contains 5%FCS
5/ well, 90uL.The every kind of compound sample (4a, 5a, 4b, 4e, 5e) that adds ConA (being concanavalin A) (10 μ g/mL) and two kinds of final concentrations of 100,25 μ M, 37 ℃, 5%CO
2Hatched under the condition 72 hours, and establish the splenocyte group that do not add sample compound splenocyte and only add ConA and be contrast, all tests all repeat 3 times at least, establish 4 multiple holes at every turn.Measure the absorbancy (A) of cell with mtt assay, calculate proliferation rate (%)=(A at the 570nm place
The administration group-A
Control group)/A
Control group* 100%.The results are shown in Figure 1.
As seen from Figure 1, chemical general formula of the present invention compound 4a, 5a, 4b, 4e, 5e shown in (I) have obvious promoter action to the lymphocytic propagation of T, and wherein compound 4e (25 μ M) effect is the most remarkable.
Embodiment 5
Get the compound 4a 5mg of embodiment 1 preparation, lactose 60mg, potato powder 30mg, polyvinyl alcohol 2mg, Magnesium Stearate 1mg is prepared into oral tablet.
The class that is intended to listed examples 1-5 of the present invention to illustrate contains chemical structure, preparation method and this compounds of class nucleoside derivates of thiazole (piperazine) alkane ketone ring to immune lymphocyte proliferation activity, embodiment singly is not the synthetic method and the immunoregulatory activity of the described concrete compound of explanation itself, also can be used for simultaneously illustrating kind and the quantity that changes raw material, synthetic its homologue and analogue, and scope of the present invention is not constituted any restriction.
Claims (9)
1. class nucleoside derivates that contains thiazole (piperazine) alkane ketone ring, its chemical general formula is shown in (I):
Wherein k is 1 or 2; M is 0 or 1; X is Sauerstoffatom or amino, R
1For hydrogen atom or hydroxyl or contain C
1-C
6The alkoxyl group of straight or branched; R
2For containing C
1-C
18Alkyl, the aryl of straight or branched.
2. the class nucleoside derivates that contains thiazole (piperazine) alkane ketone ring according to claim 1 is characterized in that said aryl is a phenyl, benzyl, the 4-p-methoxy-phenyl, the 4-aminomethyl phenyl, the 4-chloro-phenyl-, the 4-bromophenyl, the 4-iodophenyl, the 4-hydroxy phenyl, the 2-p-methoxy-phenyl, the 2-aminomethyl phenyl, the 2-chloro-phenyl-, the 2-bromophenyl, the 2-iodophenyl, the 2-hydroxy phenyl, the 3-p-methoxy-phenyl, the 3-aminomethyl phenyl, the 3-chloro-phenyl-, the 3-bromophenyl, the 3-iodophenyl, the 3-hydroxy phenyl, the 1-naphthyl, the 2-naphthyl, the 2-furyl, the 3-pyridyl, the 2-pyridyl, in the 4-pyridyl any one.
3. compound according to claim 1 is characterized in that k wherein is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be methyl.
4. the class nucleoside derivates that contains thiazole (piperazine) alkane ketone ring according to claim 1 is characterized in that k wherein is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be butyl.
5. the class nucleoside derivates that contains thiazole (piperazine) alkane ketone ring according to claim 1 is characterized in that k wherein is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be octyl group.
6. the class nucleoside derivates that contains thiazole (piperazine) alkane ketone ring according to claim 1 is characterized in that k wherein is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be octadecyl.
7. the class nucleoside derivates that contains thiazole (piperazine) alkane ketone ring according to claim 2 is characterized in that k wherein is 1; M is 0; X is a Sauerstoffatom, R
1Be methylol; R
2Be phenyl.
8. described synthesis preparation method that contains the class nucleoside derivates of thiazole (piperazine) alkane ketone ring of claim 1 is characterized in that it may further comprise the steps:
A, be starting raw material with aromatic amine or aliphatic amide, alditol, in the anhydrous methanol solvent, according to mol ratio 1.2: 1, stirring and dissolving;
B, microwave radiation or stirring at room according to mol ratio 1: 2, add the reaction of Thiovanic acid or thiohydracrylic acid, transfer pH6.5-7.5, and extraction obtains chemical general formula compound shown in (I);
Wherein k is 1 or 2; M is 0 or 1; X is Sauerstoffatom or amino, R
1For hydrogen atom or hydroxyl or contain C
1-C
6The alkoxyl group of straight or branched; R
2For containing C
1-C
18Alkyl, the aryl of straight or branched.
9. the described application of class nucleoside derivates in preparation immunomodulator pharmaceutical preparation that contains thiazole (piperazine) alkane ketone ring of claim 1.
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| CN111205240A (en) * | 2020-03-06 | 2020-05-29 | 魏彬 | Immunity regulator containing thiazolidine-4-ketone and its application |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1268140A (en) * | 1996-10-16 | 2000-09-27 | Icn药品公司 | Monocyclic L-nucleosides, analogs and uses thereof |
| CN1612889A (en) * | 2001-11-27 | 2005-05-04 | 安那迪斯药品股份有限公司 | 3-b-d-ribofuranosylthiazolo [4,5-d] pyridimine nucleosides and uses thereof |
| CN1964985A (en) * | 2004-06-07 | 2007-05-16 | 阿纳迪斯药物公司 | 3-beta-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and uses thereof |
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2011
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1268140A (en) * | 1996-10-16 | 2000-09-27 | Icn药品公司 | Monocyclic L-nucleosides, analogs and uses thereof |
| CN1612889A (en) * | 2001-11-27 | 2005-05-04 | 安那迪斯药品股份有限公司 | 3-b-d-ribofuranosylthiazolo [4,5-d] pyridimine nucleosides and uses thereof |
| CN1964985A (en) * | 2004-06-07 | 2007-05-16 | 阿纳迪斯药物公司 | 3-beta-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and uses thereof |
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| 《Bioorganic & Medicinal Chemistry Letters》 20070822 Michiko Kimoto et al. Cytostatic evaluations of nucleoside analogs related to unnatural base pairs for a genetic expansion system 第5582-5585页 1-9 第17卷, * |
| 《Bioorganic & Medicinal Chemistry Letters》 20070929 Khalid El Akri et al. Efficient synthesis and in vitro cytostatic activity of 4-substituted triazolyl-nucleosides 第6656-6659页 1-9 第17卷, * |
| 《Carbohydrate Research》 20080909 Hua Chen et al. Synthesis and biological activity of novel thiazolidin-4-ones with a carbohydrate moiety 第3015-3020页 1-9 第343卷, * |
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| 《河北大学学报(自然科学版)》 20090331 陈华等 2-羟甲基-3-芳基-1,3-噻唑烷-4-酮衍生物的微波促进合成及生物活性 第153-159页 1-9 第29卷, 第2期 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111205240A (en) * | 2020-03-06 | 2020-05-29 | 魏彬 | Immunity regulator containing thiazolidine-4-ketone and its application |
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| CN102153548B (en) | 2012-11-28 |
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