CN1425663A - Process for preparing 2-pyridyl-4-carbonyl-benzimidazole derivatives - Google Patents
Process for preparing 2-pyridyl-4-carbonyl-benzimidazole derivatives Download PDFInfo
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- CN1425663A CN1425663A CN 02155012 CN02155012A CN1425663A CN 1425663 A CN1425663 A CN 1425663A CN 02155012 CN02155012 CN 02155012 CN 02155012 A CN02155012 A CN 02155012A CN 1425663 A CN1425663 A CN 1425663A
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- pyridyl
- benzimidazolyl
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Abstract
In the preparation of 2-pyridyl-4-carbonyl-benzimidazole derivative, 2,3-diaminobenzoic acid and 3-pyridyl formaldehyde or 4-pyridyl formaldehyde are condensated to produce intermediate 2-(3-pyridyl)-4-benzimidazole or 2-(4-pyridyl)-4-benzimidazole; and the intermediate is then condensated with amine compound to produce serial products. In the compounds, pyridyl radical as alkali substitute radical with strong affinity with protein is introduced to 2-position as group A to make the compounds possess strong anticancer performance. To the aromatic group as group B, substitute group with ever high bioactivity may be introduced for preparing various compounds with ever higher bioactivity as anticancer medicine.
Description
Technical field:
The present invention is the preparation method of a kind of 2-pyridyl-4-carbonic acyl radical-benzimidazolyl type derivative, relates to the preparation of a series of novel compound benzimidazolyl type derivatives.
Background technology:
Along with the raising day by day of people's living standard, people more and more pay attention to healthy, are used to simultaneously to prevent and the R and D for the treatment of the medicine of disease develop more and more sooner.Cancer is the maximum enemy who threatens human body health at present, and the medicine of exploitation treatment cancer has become various countries researchist's heat subject, and a large amount of new compounds is designed to synthesize.The William A.Denny of Auckland, NZL pharmaceutical university etc. are at J.Med.Chem. (1990,33,814～819) publish an article and reported the preparation of 2-phenyl-4-phosphinylidyne benzimidazolyl type compound, and it is cut off agent as DNA, found that this compounds has cancer resistance, particularly have antileukemie effect, but with the linkage force of dna molecular a little less than.
Summary of the invention:
The objective of the invention is at actual demand, the preparation method of a kind of 2-pyridyl-4-carbonic acyl radical-benzimidazolyl type derivative is provided, this parallel imidazole type compound of series is carried out structural improvement, to increase the biological activity of this series compound.
Compound among the present invention has following precursor structure formula
A is for having substituting group or not having substituent 3 or 4 pyridine rings in the formula; The B representative has phenyl, alkyl, cycloalkyl, aralkyl, the aryl of halogen atom or hydrogen atom.
The preparation method of series compound of the present invention utilizes 2,3 one diaminobenzoic acids and 3 one pyridylaldehydes or 4 one pyridylaldehyde condensations make intermediate 2-(3-pyridyl)-4-benzimidazolyl or 2-(4-pyridyl)-4-benzimidazolyl, and then make series product with the aminated compounds condensation.
Their reaction process can be expressed as follows:
The preparation of intermediate (I) is finished the most handy copper salt catalyst under mantoquita or molysite catalysis.The mol ratio of reaction raw materials 3-(or 4-) pyridine aldehydes and 2,3 one diaminobenzoic acids must be greater than 1, and preferably when ratio 1.5, reaction yield is the highest.The condensation of intermediate compound I and aminated compounds can be finished in alcohol, as methyl alcohol, ethanol etc., also can finish in halogenated alkane or alkylbenzene.
The 2-position A group of compound among the present invention in molecule introduced the alkali subtituent pyridyl, and basic group and proteinic avidity are strengthened, and have stronger anti-cancer properties.
B group among the present invention has adopted aromatic group, can introduce to have more bioactive substituting group on aromatic group, can prepare the bioactive products that have more in this way more, the development PTS.
Embodiment:
Below by specific embodiment technical scheme of the present invention is further described.
Embodiment 1
With 2,3 one diaminobenzoic acids, 1.52 grams (10m mol), 100 ml methanol are added in 250 milliliters of there-necked flasks, the copper-bath that adds 28 grams 10%, be warming up to backflow, under refluxad add 2 grams, 3 one pyridylaldehydes, keep half an hour after, filter, filter cake washes with water, dries to such an extent that white crystals 1.52 restrains yield 61%.
Product is through mass spectroscopy: M
+=239;
Results of elemental analyses, calculated value: C 65.27%; H 3.77; N 17.57%.Measured value: C 64.97%; H 3.72; N 17.17%.
Embodiment 2
With 2,3 one diaminobenzoic acids, 1.52 grams (10m mol), 100 ml methanol are added in 250 milliliters of there-necked flasks, the copper-bath that adds 28 grams 10%, be warming up to backflow, under refluxad drip 2 the gram 4 one pyridylaldehydes, the insulation half an hour after, filter, filter cake washes with water, dries to such an extent that white crystals 1.58 restrains yield 63.4%.
Product is through mass spectroscopy: M
+=239;
Results of elemental analyses, calculated value: C 65.27%; H 3.77; N 17.57%.Measured value: C 65.10%; H3.69; N 17.27%.
Embodiment 3
Take by weighing compound 0.66 gram (27.6mmol) of preparation in the experiment 1,25 gram methylene dichloride are added in 100 milliliters of there-necked flasks, cool to 0 with frozen water, add 3-chloroaniline 0.36 gram, be warming up to room temperature, stir after 24 hours, add 1 gram water, stirred 4 hours, and filtered, boil off the solvent in the mother liquor after, separate out colourless crystallization, filter, oven dry obtains 0.25 gram product.Yield 26.1%.
Product is through mass spectroscopy: M
+=348
The proton nmr spectra result: H-NMR δ: 7.21-7.24 (d, 1H), 7.45-7.51 (t, 2H), 7.65-7.72 (t, 2H), 7.87-7.90 (d, 1H), 8.01-8.04 (d, 1H), 8.22 (d, 1H), and 8.64-8.66 (t, 2H), 8.77-8.79 (t, 2H), 9.49 (s, 1H), 12.20 (s, 1H).
Embodiment 4～10
Adopt example 3 same methods can synthesize following compounds (as shown in table 1).
Position substituting group 42 CH of table 1 compound sequence number substituent X
352 Cl6,2 F7,3 CH
384 CH
394 Cl10,4 F
Embodiment 11～18
Can synthesize following compounds (as shown in table 2) according to embodiment 3 same synthetic methods
Position substituting group 11 2 CH of table 2 compound sequence number substituent X
312 2 Cl13,2 F14,3 CH
315 3 Cl16,4 CH
317 4 Cl18,4 F
Claims (2)
1, the preparation method of a kind of 2-pyridyl-4-carbonic acyl radical-benzimidazolyl type derivative; it is characterized in that utilizing 2; 3 one diaminobenzoic acids and 3 one pyridylaldehydes or 4 one pyridylaldehyde condensations make intermediate 2-(3-pyridyl)-4-benzimidazolyl or 2-(4-pyridyl)-4-benzimidazolyl; and then make series product with the aminated compounds condensation, its reaction process is expressed as follows:
Wherein, the preparation of intermediate (I) is finished under mantoquita or molysite catalysis, and the mol ratio of reaction raw materials 3-(or 4-) pyridine aldehydes and 2,3 one diaminobenzoic acids is greater than 1, the condensation of intermediate compound I and aminated compounds is finished in alcohol, or finishes in halogenated alkane or alkylbenzene.
2, as the preparation method of the said 2-pyridyl of claim 1-4-carbonic acyl radical-benzimidazolyl type derivative, the mol ratio that it is characterized in that reaction raw materials 3-(or 4-) pyridine aldehydes and 2,3 one diaminobenzoic acids is 1.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02155012 CN1425663A (en) | 2002-12-19 | 2002-12-19 | Process for preparing 2-pyridyl-4-carbonyl-benzimidazole derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02155012 CN1425663A (en) | 2002-12-19 | 2002-12-19 | Process for preparing 2-pyridyl-4-carbonyl-benzimidazole derivatives |
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|---|---|
| CN1425663A true CN1425663A (en) | 2003-06-25 |
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| CN 02155012 Pending CN1425663A (en) | 2002-12-19 | 2002-12-19 | Process for preparing 2-pyridyl-4-carbonyl-benzimidazole derivatives |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010078830A1 (en) * | 2009-01-08 | 2010-07-15 | 上海交通大学 | Benzimidazole-4-carboxamide derivatives, their preparation methods, pharmaceutical compositions and their uses |
| US8846947B2 (en) | 2008-07-03 | 2014-09-30 | Glaxosmithkline Llc | Benzimidazoles and related analogs as sirtuin modulators |
-
2002
- 2002-12-19 CN CN 02155012 patent/CN1425663A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8846947B2 (en) | 2008-07-03 | 2014-09-30 | Glaxosmithkline Llc | Benzimidazoles and related analogs as sirtuin modulators |
| WO2010078830A1 (en) * | 2009-01-08 | 2010-07-15 | 上海交通大学 | Benzimidazole-4-carboxamide derivatives, their preparation methods, pharmaceutical compositions and their uses |
| JP2012514607A (en) * | 2009-01-08 | 2012-06-28 | シャンハイ ジアオ トン ユニバーシティ | Benzimidazole-4-carboxamide derivative and method for producing the same, drug mixture and use thereof |
| RU2558328C2 (en) * | 2009-01-08 | 2015-07-27 | Шанхай Цзяо Тун Юниверсити | Banzimidazol-4-amide derivatives, methods for producing them, based pharmaceutical compositions and using them as coxsackie virus agent |
| EP2963033A1 (en) * | 2009-01-08 | 2016-01-06 | Shanghai Jiao Tong University | Benzimidazole-4-carboxamide derivates, their preparation methods, pharmaceutical compositions and their uses |
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