CN101948423A - Phenyl methanesulfonamide derivant and preparation method thereof - Google Patents
Phenyl methanesulfonamide derivant and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a phenyl methanesulfonamide derivant and a preparation method thereof, belonging to the technical field of organic chemistry and drug synthesis. The chemical name of the phenyl methanesulfonamide derivant is N-[2-n-propoxy-4(1-(2,2'-bipyridine methyl) amido) acetamido] phenyl methanesulfonamide, and the structural formula thereof is shown in the specification; the preparation method of the phenyl methanesulfonamide derivant comprises the following steps: taking 2-amino-5-nitrophenol as a raw material, and carrying out phenolic hydroxyl group alkylate reaction, amino mesylation reaction, nitryl reduction reaction, amino bromine acetylation reaction and N-alkylation reaction to obtain the phenyl methanesulfonamide derivant, wherein the phenyl methanesulfonamide derivant can be used as a [<99m>Tc(CO)3]<+>labeled precursor compound, and realizes the purpose of tumour SPECT development diagnosis.
Description
Technical field
The present invention relates to a kind of phenyl methanesulfonamide amide derivatives and preparation method thereof, belong to organic chemistry and technical field of medicine synthesis.
Background technology
Cancer and cardiovascular and cerebrovascular diseases are classified as the principal disease of two class serious threat human healths jointly.In the middle of all cancers, mammary cancer is a kind of malignancy disease of serious threat women's health.2006, global women because of the lethal mortality ratio of mammary cancer reach the patient with breast cancer overall 28.6%.In recent years, the M ﹠ M of mammary cancer all over the world all has increase, serious threat women's physical and mental health.
According to the tumour tertiary prevention principle radical cure of case (causal prophylaxis, examination or generaI investigation, the progressive stage), its secondary prevention is particularly important, and promptly early looking into, early examining is that the control cancer takes place and the effective measure of development.Therefore, the research of the early stage diagnosis and treatment medicine of mammary cancer just being become key, is the basis that the patient with breast cancer was in time treated and obtained good efficacy, also is the important factor that reduces mortality ratio, prolongs lifetime.Usually, early diagnosis of tumor measure Evaluation of accuracy is comprised susceptibility and specificity two big indexs, susceptibility is low can be caused failing to pinpoint a disease in diagnosis in a large number of tumour and loses the early diagnosis meaning, the low accuracy and the efficient that then can influence early diagnosis of specificity, thus reduce its using value.
2006, people such as U.S. Bin Su have reported expression and activity research (the document 1:Bin Su of a series of aromatase inhibitor phenyl methanesulfonamide amide substances in breast cancer cell, et, al. Novel Sulfonanilide Analogues Suppress Aromatase Expression and Activity in Breast Cancer Cells Independent of COX-2 Inhibition. Journal of Medicinal Chemistry. 2006,49 (4), 1413-1419.).After this, this seminar has successively reported synthetic and biological evaluation (the document 2:Bin Su of novel phenyl methanesulfonamide amides as anti-breast cancer medicines in 2008, et, al. Synthesis and Biological Evaluation of Novel Sulfonanilide Compounds as Antiproliferative Agents for Breast Cancer, Journal of Combinatorial Chemistry. 2008,10,475 – 483), and the antitumor drug effect research of such material of different substituents (document 3:Bin Su, et, al. Novel Sulfonanilide Analogs Decrease Aromatase Activity in Breast Cancer Cells:Synthesis, Biological Evaluation, and Ligand-Based Pharmacophore Identification. Journal of Medicinal Chemistry.2008,51,1126 – 1135).The result shows that this compounds has higher specificity and susceptibility to breast cancer cell, because of the different aromatase inhibitor activity that have in various degree of substituting group.Shown in the following reaction formula I of synthetic route of the phenyl methanesulfonamide acid amides of this seminar's design:
Ⅰ
2007, the people such as Min Wang of medical college of Indiana, USA university radiation subject invented usefulness
11C mark phenyl methanesulfonamide amides makes it become potential PET developer.(document 4:Min Wang, et, al. Synthesis of carbon-11 labeled sulfonanilide analogues as new potential PET agents for imaging of aromatase in breast cancer. Bioorganic ﹠amp; Medicinal Chemistry Letters. 2007,17,332 – 336).Its mentality of designing is shown in the reaction formula II:
Ⅱ
1998, people such as the breadboard Roger Alberto of Switzerland Paul Scherrer institute photopharmacology invented a kind of new organometallic complex [
99mTc(H
2O)
3(CO)
3]
+(document 5:Roger Alberto, et, al. A novel organometallic aqua complex of Technetium for the labeling of biomolecules:synthesis of [
99mTc(H
2O)
3(CO)
3]
+From [
99mTcO
4]
-In aqueous solution and its reaction with a bifunctional ligand. Journal of Medicinal Chemistry.1998,120,7987 – 7988).This title complex is because of its unique carbonyl technetium core texture feature, can with three water moleculess in the suitable tridentate ligand exchange intermediate of flexibility, form the higher title complex of spatial stability.Calendar year 2001, the people such as Jiang Yan of department of chemistry of Beijing Normal University invent usefulness [
99mTc(CO)
3]
+The myocardium medicine that mark has a tridentate ligand obtain a kind of complex compound [
99mTc(CO)
3(MIBI)
3]
+, and as the potential myocardial developer be applied to pharmaceutical research (Jiang Yan etc. a kind of new
99mThe Tc mark [
99mTc(CO)
3(MIBI)
3]
+Complex compound is as myocardial developer. Science Bulletin, and 2001,46(9), 727-730).
In sum, the phenyl methanesulfonamide amide substance has the function that suppresses aromatase enzyme level in the breast cancer cell to some extent because of substituting group is different, have tridentate ligand group can with [
99mTc(CO)
3]
+Complexing.
Summary of the invention
The purpose of this invention is to provide a kind of new phenyl methanesulfonamide amide derivatives N-[2-positive propoxy-4(1-(2,2 '-bipyridine methyl) amido) acetamido] the phenyl methanesulfonamide acid amides, and preparation method thereof, for follow-up to this compound [
99mTc(CO)
3]
+Marker research and biological property research lay the foundation.
In order to solve the problems of the technologies described above, the invention provides following technical scheme:
A kind of phenyl methanesulfonamide amide derivatives, chemical name are N-[2-positive propoxy-4(1-(2,2 '-bipyridine methyl) amido) acetamido] the phenyl methanesulfonamide acid amides, its structural formula is as follows:
C
24H
29N
5O
4S, M=483; Physico-chemical property is: pale red brown oily liquids, uv-absorption maximum wavelength are 257 nm, poorly water-soluble, and solvability is better in the ethanol, and the solubleness in ethanol is 43.6 g/100mL.
The preparation method of above-mentioned phenyl methanesulfonamide amide derivatives; with 2-amino-5 nitrophenols is raw material; finish through phenolic hydroxyl group alkylated reaction, amino methylsulfonyl reaction, nitro-reduction reaction, amino acetobrom reaction and five steps of N-alkylated reaction, its reaction process is:
A, phenolic hydroxyl group alkylated reaction: with the amino 5-nitrophenols of 1-N-PROPYLE BROMIDE, propyl iodide or n-propyl chloride and 2-in dry DMF or dehydrated alcohol, in anhydrous K
2CO
3Under the effect, reacting by heating, CH
2Cl
2Extractive reaction liquid and column chromatography for separation get 2-propoxy--4 N-methyl-p-nitroaniline a; Wherein the mol ratio of amino 5-nitrophenols of 2-and halogenopropane is 1:1～2;
B, amino methylsulfonyl reaction: methylsulfonyl chloride and 2-propoxy--4 N-methyl-p-nitroaniline a are at anhydrous CH
2Cl
2In, in pyridine or anhydrous K
2CO
3Effect reaction down, alkali lye extractive reaction liquid, crystallization gets N-(2-propoxy--4 nitro) phenyl methanesulfonamide acid amides b; 2-propoxy--4 N-methyl-p-nitroaniline wherein: the mol ratio of methylsulfonyl chloride is 1:2～3;
C, nitro-reduction reaction: with N-(2-propoxy--4 nitro) the phenyl methanesulfonamide acid amides is with the reduction of Pd/C shortening or ferrous acid, N-(2-propoxy--4 amino) phenyl methanesulfonamide acid amides c;
D, amino acetobrom reaction: N-(2-propoxy--4 amino) phenyl methanesulfonamide acid amides and bromoacetyl bromide are at anhydrous CH
2Cl
2Or 1, in the 4-dioxane, under the triethylamine effect, react, reaction solution gets N-(2-propoxy--4-acetobrom amino through column chromatography for separation) phenyl methanesulfonamide acid amides d; Wherein, phenyl methanesulfonamide acid amides N-(2-propoxy--4 amino): the mol ratio of bromoacetyl bromide is 1:2～3;
E, N-alkylated reaction: phenyl methanesulfonamide acid amides and 2 N-(2-propoxy--4-acetobrom amino), 2 '-bipyridine methyl amine is in acetone, at K
2CO
3With KI effect reaction down, the reaction solution column chromatography for separation gets N-[2-positive propoxy-4(1-(2,2 '-bipyridine methyl) amido) acetamido] phenyl methanesulfonamide acid amides e; Wherein, N-(2-propoxy--4-acetobrom amino) the phenyl methanesulfonamide acid amides: 2, the mol ratio of 2 '-bipyridine methyl amine is 1:1～1.5.
The synthetic method of compound (a) is consistent with document 1 report; Compound (b) adopts pyridine to do acid binding agent, CH
2Cl
2Make solvent, with document 1 report do acid binding agent with NaH, DMF makees solvent and carries out optimization of process conditions, original technology is extremely strong because of the NaH activity, reaction system requires no water treatment; The DMF boiling point is higher, and product is difficult for handling.Reaction conditions gentleness behind process optimization, simple to operate.Both effectively reduced cost, improved productive rate again.
Compound (c), (d) and (e) be the new compound that designs and synthesizes out voluntarily, target product (e) can be used as [
99mTc(H
2O)
3(CO)
3]
+The precursor compound of mark.The present invention introduces bifunctional chelating agent (that is: tridentate ligand 2,2 '-bipyridine methyl amine) on the basis of synthesis of phenyl Toluidrin, obtain a labelled precursor compound (e), in the hope of make this labelled precursor can by isotropic substance [
99mTc(CO)
3]
+Mark forms stable title complex.Theoretically: contain phenyl methanesulfonamide acid amides active medicine group (document 1) in this tagged compound to the propyl group replacement of breast cancer cell susceptibility, its portability nucleic arrives cancer cells after introducing difunctional intercalating agent, combine with corresponding receptor-specific, make medicine at the tumour unconventionality expression but clinical symptom is not carried out video picture before occurring as yet, reach the purpose of early diagnosis.Thereby the development of this target compound can be seek a kind of mammary cancer is had than hypersensitivity and specificity, toxic side effect is little and price is low diagnostic medicine lay the foundation.
Description of drawings
Accompanying drawing is used to provide further understanding of the present invention, and constitutes the part of specification sheets, is used from explanation the present invention with embodiments of the invention one, is not construed as limiting the invention.In the accompanying drawings:
Fig. 1 is the mass spectrum of product (d);
Fig. 2 is product (d)
1H-NMR figure;
Fig. 3 is the mass spectrum of product (e);
Fig. 4 is the part of product (e)
1H-NMR figure 1.;
Fig. 5 is the part of product (e)
1H-NMR figure 2..
Embodiment
Below in conjunction with accompanying drawing the preferred embodiments of the present invention are described, should be appreciated that preferred embodiment described herein only is used for description and interpretation the present invention, and be not used in qualification the present invention.
Total synthetic route is as follows:
Synthesizing of embodiment 1:2-propoxy--4 N-methyl-p-nitroaniline
With the amino 5-nitrophenols of 7.7 g (50 mmol) 2-, 7 g anhydrous K
2CO
3Add in the three-necked flask of 250 mL with 100 mL dry DMF, Dropwise 5 .4 mL1-N-PROPYLE BROMIDE (60 mmol) at 160 ℃ of following back flow reaction 4 h, cools off while stirring, adds suitable quantity of water and saturated Na
2CO
3Solution extinguishes reaction, uses CH
2Cl
2Extractive reaction liquid, layering, organic phase is successively used saturated Na
2CO
3Solution and water washing, anhydrous MgSO
4Drying is filtered, filtrate decompression distill reddish-brown thickness oily matter, oily matter is made developping agent with ethyl acetate and normal hexane (1:6) and is carried out silica gel column chromatography and get yellow solid 2-propoxy--4 N-methyl-p-nitroaniline 8.21 g.Productive rate: 83.7%, mp:59～61 ℃, MS:197(M+1),
1H-NMR(400Mz, CDCl
3): 7.80(1H, d, J=8.7,2.1Hz), 7.67(1H, s), 7.26(2H, s), and 6.60(1H, d, J=8.7,2.3Hz), and 4.05(2H, t, J=6.6Hz), 1.90(2H, m), 1.07 (3H, t, J=7.5Hz).Ultimate analysis value (calculated value)/%:C:55.09%, H:6.16%, N:14.28%; (measured value)/%:C:55.23%, H:6.02%, N:14.52%.
Embodiment 2:N-(2-propoxy--4 nitro) the phenyl methanesulfonamide acid amides is synthetic
With 4.9 g(25 mmol) 2-propoxy--4 N-methyl-p-nitroaniline, 3 mL pyridines and the anhydrous CH of 100 mL
2Cl
2Add in the three-necked flask, drip 4.8 mL methylsulfonyl chlorides (62.5 mmol) while stirring, reaction 48 h under the room temperature, use 100 mL 10%NaOH solution extractions afterwards, layering, water is regulated pH to 1～2 with 1 M hydrochloric acid, there is yellow solid to separate out, filter, yellow solid gets yellow solid 5.19 g with the NaOH solution of 1 M and the hydrochloric acid soln recrystallization of 1 M.Productive rate: 81.8%, mp:121～123 ℃, MS:297(M+Na),
1H-NMR(400Mz, CDCl
3): 7.91(1H, d, J=8.1,2.3Hz), 7.78(1H, s), and 7.65(1H, d, J=8.8,2.3Hz), 7.24(1H, br), and 4.12(2H, t, J=6.6Hz), 3.11(3H, s), 1.90 (2H, m), 1.08 (3H, t, J=2.1,7.3,2.1Hz).Ultimate analysis value (calculated value)/%:C:43.79%, H:5.14, N:10.21%; (measured value)/%:C:44.02%, H:5.08%, N:10.01%.
Embodiment 3:N-(2-propoxy--4 amino) the phenyl methanesulfonamide acid amides is synthetic
Get 2.74 g (10 mmol) N-(2-propoxy--4 nitro) phenyl methanesulfonamide acid amides and 100 mL methyl alcohol are in three-necked flask, after wherein adding 1 mL concentrated hydrochloric acid, add 2 g iron powders, 55 ℃ of following mechanical stirring 2 h remove by filter iron powder, filtrate concentrate faint yellow solid 1.81 g.Productive rate: 73.8%, mp:108 ℃ begins distillation, and 155 ℃ of colors begin to deepen until becoming black.
Embodiment 4:N-(2-propoxy--4-acetobrom amino) the phenyl methanesulfonamide acid amides is synthetic
With 2.44 g (10 mmol) N-(2-propoxy--4 amino) the phenyl methanesulfonamide acid amides is dissolved in 100 mL CH
2Cl
2In, cryosel is bathed down and is slowly dripped with 20 mL CH while stirring
2Cl
22 mL bromoacetyl bromides (27mmol) of dilution drip afterwards by 20 mL CH again
2Cl
22 mL triethylamines of dilution rise under the room temperature reaction 24 h after half an hour, filter, filtrate concentrate reddish-brown thickness oily matter, with the concentrated solution ethyl acetate: sherwood oil (1:2) is made developping agent and is carried out silica gel column chromatography, gets white solid 1.65 g.Productive rate: 45.2%, mp:117～119 ℃, MS:365(M+1) [or 67(M+1), annotate: the isotopic peak of Br], as shown in Figure 1 and Figure 2,
1H-NMR(400Mz, CDCl
3): 7.56(1H, s), 7.48(1H, d, J=9.6,2.1Hz), 7.26(1H, s), 6.83(1H, d, J=8.7Hz), 6.67(1H, s), 4.19(2H, s), 4.02(2H, t, J=4.5,7.1,4.3Hz), 2.93(3H, s), 1.85(2H, m), 1.05(3H, t, J=2.3,7.5,2.1).Ultimate analysis value (calculated value)/%:C:39.46%, H:4.69%, N:7.67%; (measured value)/%:C:39.76%, H:5.12%, N:7.84%.
Embodiment 5:N-[2-positive propoxy-4(1-(2,2 '-bipyridine methyl) acetamido amido)] phenyl methanesulfonamide acid amides synthetic
Get 1.82 g (5 mmol) N-(2-propoxy--4-acetobrom amino) phenyl methanesulfonamide acid amides, 1.38 g K
2CO
3, 0.18 g KI and 60 mL acetone add in the three-necked flask, again to wherein slowly dripping 1.25g 2,2 '-bipyridine methyl amine (6.25 mmol), reaction 6 h under the room temperature, filter, underpressure distillation gets reddish-brown thickness oily matter, through silica gel column chromatography (the developping agent ethyl acetate: dehydrated alcohol=6:1) pale red brown oil 1.28 g.Productive rate: 52.9%, MS:484(M+1), as Fig. 2-shown in Figure 5,
1H-NMR(400Mz, CDCl
3): 8.62(2H, d, J=4.2Hz), 7.87(1H, d, J=2.0Hz), 7.63(2H, m), 7.49 (1H, s, NH), 7.46(1H, s, NH), 7.29(2H, d, J=2.1Hz), 7.27(1H, s), 7.20(2H, m), 7.11(1H, d, J=6.5Hz), 4.04 (2H, t, J=6.4,6.6,9.1Hz), 3.93(4H, s), 3.47(2H, s), 2.90(3H, s), 1.84(2H, m), 1.03(3H, t, J=7.4Hz), [2.04(3H, s), 4.11(2H, q), 1.26(3H, t), (CH
3COOCH
2CH
3)] [1.38(3H, t), 3.70(2H, q), (CH
3CH
2OH)] ultimate analysis value (calculated value)/%:C:59.61%, H:6.04%, N:14.48%; (measured value)/%:C:59.55%, H:6.32%, N:14.62%.
It should be noted that at last: the above only is the preferred embodiments of the present invention, be not limited to the present invention, although the present invention is had been described in detail with reference to previous embodiment, for a person skilled in the art, it still can be made amendment to the technical scheme that aforementioned each embodiment put down in writing, and perhaps part technical characterictic wherein is equal to replacement.Within the spirit and principles in the present invention all, any modification of being done, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (7)
1. phenyl methanesulfonamide amide derivatives, chemical name is N-[2-positive propoxy-4(1-(2,2 '-bipyridine methyl) amido) acetamido] the phenyl methanesulfonamide acid amides, its structural formula is as follows:
2. the preparation method of the described phenyl methanesulfonamide amide derivatives of claim 1; it is characterized in that: with 2-amino-5 nitrophenols is raw material; finish through phenolic hydroxyl group alkylated reaction, amino methylsulfonyl reaction, nitro-reduction reaction, amino acetobrom reaction and five steps of N-alkylated reaction, its reaction process is:
A, phenolic hydroxyl group alkylated reaction: with the amino 5-nitrophenols of 1-N-PROPYLE BROMIDE, propyl iodide or n-propyl chloride and 2-in dry DMF or dehydrated alcohol, in anhydrous K
2CO
3Under the effect, reacting by heating, CH
2Cl
2Extractive reaction liquid and column chromatography for separation get 2-propoxy--4 N-methyl-p-nitroaniline a; The amino 5-nitrophenols of 2-wherein: the mol ratio of halogenopropane is 1:1～2;
B, amino methylsulfonyl reaction: methylsulfonyl chloride and 2-propoxy--4 N-methyl-p-nitroaniline a are at anhydrous CH
2Cl
2In, in pyridine or anhydrous K
2CO
3Effect reaction down, alkali lye extractive reaction liquid, crystallization gets N-(2-propoxy--4 nitro) phenyl methanesulfonamide acid amides b; 2-propoxy--4 N-methyl-p-nitroaniline wherein: the mol ratio of methylsulfonyl chloride is 1:2～3;
C, nitro-reduction reaction: with N-(2-propoxy--4 nitro) the phenyl methanesulfonamide acid amides is with the reduction of Pd/C shortening or ferrous acid, N-(2-propoxy--4 amino) phenyl methanesulfonamide acid amides c;
D, amino acetobrom reaction: N-(2-propoxy--4 amino) phenyl methanesulfonamide acid amides and bromoacetyl bromide are at anhydrous CH
2Cl
2Or 1, in the 4-dioxane, under the triethylamine effect, react, reaction solution gets N-(2-propoxy--4-acetobrom amino through column chromatography for separation) phenyl methanesulfonamide acid amides d; Wherein, phenyl methanesulfonamide acid amides N-(2-propoxy--4 amino): the mol ratio of bromoacetyl bromide is 1:2～3;
E, N-alkylated reaction: phenyl methanesulfonamide acid amides and 2 N-(2-propoxy--4-acetobrom amino), 2 '-bipyridine methyl amine is in acetone, at K
2CO
3With KI effect reaction down, the reaction solution column chromatography for separation gets N-[2-positive propoxy-4(1-(2,2 '-bipyridine methyl) amido) acetamido] phenyl methanesulfonamide acid amides e; Wherein, N-(2-propoxy--4-acetobrom amino) the phenyl methanesulfonamide acid amides: 2, the mol ratio of 2 '-bipyridine methyl amine is 1:1～1.5.
3. the preparation method of phenyl methanesulfonamide amide derivatives according to claim 2 is characterized in that: described steps A is specially, with the amino 5-nitrophenols of 2-, anhydrous K
2CO
3Join in the dry DMF, add the 1-N-PROPYLE BROMIDE, back flow reaction, cooling adds suitable quantity of water and saturated Na
2CO
3The solution stopped reaction, CH
2Cl
2Extractive reaction liquid, layering, organic phase is successively used saturated Na
2CO
3Solution and water washing, drying is filtered, filtrate decompression distill reddish-brown thickness oily matter, oily matter is made developping agent with ethyl acetate and normal hexane (1:6), gets yellow solid 2-propoxy--4 N-methyl-p-nitroaniline a through silica gel column chromatography.
4. the preparation method of phenyl methanesulfonamide amide derivatives according to claim 2 is characterized in that: described step B is specially, and 2-propoxy--4 N-methyl-p-nitroaniline, pyridine are joined anhydrous CH
2Cl
2In, add methylsulfonyl chloride, react under the room temperature, with NaOH solution extraction reaction solution, layering, water is regulated pH to strongly-acid with 1 M hydrochloric acid, there is yellow solid to separate out, filter, yellow solid gets yellow solid N-(2-propoxy--4 nitro with NaOH solution and hydrochloric acid soln recrystallization) phenyl methanesulfonamide acid amides b.
5. the preparation method of phenyl methanesulfonamide amide derivatives according to claim 2, it is characterized in that: described step C is specially, with N-(2-propoxy--4 nitro) the phenyl methanesulfonamide acid amides is dissolved in the methyl alcohol, to wherein successively adding concentrated hydrochloric acid, iron powder, stir, remove by filter iron powder, filtrate concentrate faint yellow solid N-(2-propoxy--4 amino) phenyl methanesulfonamide acid amides c.
6. the preparation method of phenyl methanesulfonamide amide derivatives according to claim 2 is characterized in that: described step D is specially, with N-(2-propoxy--4 amino) the phenyl methanesulfonamide acid amides is dissolved in CH
2Cl
2In, cooling adds bromoacetyl bromide down, add triethylamine afterwards, rise under the room temperature and react, filter, filtrate concentrate reddish-brown thickness oily matter, with the oily matter ethyl acetate: sherwood oil 1:2 makees developping agent and carries out silica gel column chromatography, must white solid N-(2-propoxy--4-acetobrom amino) phenyl methanesulfonamide acid amides d.
7. the preparation method of phenyl methanesulfonamide amide derivatives according to claim 2 is characterized in that: described step e is specially, with N-(2-propoxy--4-acetobrom amino) phenyl methanesulfonamide acid amides, K
2CO
3, KI joins in the acetone, again to wherein adding 2,2 '-bipyridine methyl amine, react under the room temperature, filter, underpressure distillation gets reddish-brown thickness oily matter, and oily matter is through ethyl acetate: the silica gel column chromatography that dehydrated alcohol 6:1 makees developping agent gets pale red brown oil N-[2-positive propoxy-4(1-(2,2 '-bipyridine methyl) amido) acetamido] phenyl methanesulfonamide acid amides e.
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|---|---|---|---|---|
| CN102432531A (en) * | 2010-09-09 | 2012-05-02 | 江苏省原子医学研究所 | Phenylmethanesulfonamide derivative and its preparation method |
| CN102775332A (en) * | 2012-07-12 | 2012-11-14 | 浙江工业大学 | Preparation method of N-substituted sulfonamides compounds |
| CN103172548A (en) * | 2011-12-20 | 2013-06-26 | 天津市国际生物医药联合研究院 | Preparation method and application of methanesulfonamide compound |
| CN103172548B (en) * | 2011-12-20 | 2016-11-30 | 天津市国际生物医药联合研究院 | The preparation of Methanesulfomide compounds and application thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102432531A (en) * | 2010-09-09 | 2012-05-02 | 江苏省原子医学研究所 | Phenylmethanesulfonamide derivative and its preparation method |
| CN103172548A (en) * | 2011-12-20 | 2013-06-26 | 天津市国际生物医药联合研究院 | Preparation method and application of methanesulfonamide compound |
| CN103172548B (en) * | 2011-12-20 | 2016-11-30 | 天津市国际生物医药联合研究院 | The preparation of Methanesulfomide compounds and application thereof |
| CN102775332A (en) * | 2012-07-12 | 2012-11-14 | 浙江工业大学 | Preparation method of N-substituted sulfonamides compounds |
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