CN105820071A - N-{4-[3-(4-bromo-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-methanesulfonamide new compound and preparation method and application thereof - Google Patents
N-{4-[3-(4-bromo-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-methanesulfonamide new compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN105820071A CN105820071A CN201510001141.XA CN201510001141A CN105820071A CN 105820071 A CN105820071 A CN 105820071A CN 201510001141 A CN201510001141 A CN 201510001141A CN 105820071 A CN105820071 A CN 105820071A
- Authority
- CN
- China
- Prior art keywords
- compound
- phenyl
- solvent
- reactions steps
- diethoxy
- 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.)
- Pending
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a new compound. The name of the compound is N-{4-[3-(4-bromo-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-methanesulfonamide; molecular weight of the compound is 486.3; and structure of the compound is as shown in the structural formula (compound 1). Meanwhile, the invention provides a preparation method of the compound 1. The compound provided by the invention has good drug-likeness and can be used in the research field of new drugs, especially in the research field of type-II diabetes innovative drugs.
Description
Technical field
The present invention relates to a kind of N-{4-of offer [the bromo-phenyl of 3-(4-)-ureidomethy]-2,5-diethoxy-phenyl }-Methanesulfomide noval chemical compound, preparation method and the purposes in innovation drug research thereof, this compound molecular weight is little, novel structure, stable in properties, simple in construction, it is adaptable to innovation drug research is developed, and belongs to technical field of chemistry.
Background technology
Carbamide compounds () when being combined with drug target molecule (macromole such as protein, enzyme) active pocket, owing to the hydrogen atom on nitrogen-atoms in urea groups structure is can critical amino acid residues is combined in drug target molecular activity pocket good hydrogen-bond donor, and carbonyl is the good hydrogen bond receptor that critical amino acid residues is combined in drug target molecular activity pocket in its urea groups, therefore in the compound design of innovation drug research, such group is good dominant group.Compound N-and 4-[the bromo-phenyl of 3-(4-)-ureidomethy]-2,5-diethoxy-phenyl }-Methanesulfomide is the carbamide compounds containing urea groups structure, this compound structure is novel, stable in properties, simple in construction, in the docking research of Computer-Aided Drug Design, find that this compound can have preferably combination with the drug target of some type ii diabetes, there is certain innovation drug research DEVELOPMENT PROSPECT.
Summary of the invention
1, a kind of noval chemical compound, it is characterized in that, and the entitled N-{4-of this compound [the bromo-phenyl of 3-(4-)-ureidomethy]-2,5-diethoxy-phenyl }-Methanesulfomide (compound 1), the molecular weight of this compound is 486.3, and the structural formula of this compound is shown in following formula: compound 1.
2, one prepares noval chemical compound N-{4-[the bromo-phenyl of 3-(4-)-ureidomethy]-2,5-diethoxy-phenyl } method of-Methanesulfomide, it is characterized in that, show following the most totally 3 reactions steps of reactions steps g, reactions steps h, reactions steps i including following reaction scheme 1:
The condition of reactions steps g is: para-bromoaniline and compound G molar ratio range are 0.8:1 ~ 1.3:1, triethylamine and compound G mol ratio=0.8:1 ~ 5:1), solvent is N, N dimethylformamide or dimethyl sulfoxide or acetone or 1, single solvent or the combinations of solvent such as 4 dioxane, reaction temperature is 50 ~ 120 degree, and the response time is 5 ~ 18 hours, reaction is purified to obtain product compound H, yield spectra 50% ~ 90% through concentrate, extract, crystallization etc. after terminating；The condition of reactions steps h is: Nickel dichloride hexahydrate and compound H molar ratio range are 0.9:1 ~ 2.5:1, sodium borohydride and compound H molar ratio range are 0.9:1 ~ 4:1, solvent is dichloromethane or the single solvent such as oxolane or ether or the combination of solvent, response time is 10 minutes ~ 12 hours, reaction is purified to obtain product compound I, yield spectra 50% ~ 95% through extraction, crystallization etc. after terminating；The condition of reactions steps i is: alkyl sulfonyl chloride and compound I molar ratio range are 0.8:1 ~ 1.5:1, pyridine and compound I molar ratio range are 0.9:1 ~ 1.5:1, solvent is dichloromethane or oxolane or ether or N, N dimethylformamide or dimethyl sulfoxide or acetone or 1, single solvent or the combinations of solvent such as 4 dioxane, reaction temperature is 0 ~ 80 degree, 3 ~ 18 hours response time, reaction is purified to obtain product compound 1, yield spectra 50% ~ 95% through extraction, crystallization, column chromatography etc. after terminating.
3, the compound that the present invention provides has good quasi-medicated property, can be used for new drug research field and especially treats type ii diabetes field of innovative medicine research.
4, a kind of pharmaceutical composition, including the compound described in the claim 1 of therapeutically effective amount or its pharmaceutically acceptable salt.
5, pharmaceutical composition according to claim 4, is characterized in that, this pharmaceutical composition contains one or more pharmaceutically acceptable carrier or excipient further.
6, pharmaceutical composition according to claim 4, is characterized in that, described compound or its pharmaceutically acceptable salt account for gross weight ratio 50% ~ 99.5% as active component.
Below in conjunction with specific embodiment, the present invention is further elaborated, but is not intended to the present invention.
Specific embodiment
Embodiment 1:N-{4-[the bromo-phenyl of 3-(4-)-ureidomethy]-2,5-diethoxy-phenyl } structural formula of-Methanesulfomide (compound 1) is as follows:
The synthetic route of compound N-{ 4-[the bromo-phenyl of 3-(4-)-ureidomethy]-2,5-diethoxy-phenyl }-Methanesulfomide is as follows:
Compound N-and 4-[the bromo-phenyl of 3-(4-)-ureidomethy]-2, 5-diethoxy-phenyl } the concrete preparation method of-Methanesulfomide is as follows: reactions steps g:(2, 5-diethoxy-4-Nitro-benzyl)-phenyl carbamates (0.5g, 1.39mmol), 4-bromo-aniline (239mg, 1.39mmol) with triethylamine (1.40g, 13.9mmol) add in the eggplant type bottle of 100ml, add dioxanes, it is heated to 60-80 DEG C, reaction is overnight, reaction is concentrated under reduced pressure to give crude product after terminating, recrystallization is carried out with methanol, obtain the bromo-phenyl of sterling 1-(3-)-3-(2, 5-diethoxy-4-Nitro-benzyl)-urea (480mg, productivity 78.9%)；nullReactions steps h: by bromo-for 1-(4-phenyl)-3-(2,5-diethoxy-4-Nitro-benzyl)-urea (400mg,0.91mmol) add in the eggplant type bottle of 100ml，Add methanol，Add Nickel dichloride hexahydrate (371mg，1.56mmol)，After being completely dissolved，Add sodium borohydride (119mg，3.12mmol)，Room temperature reaction 5-10 minute，Reaction carries out concentrating under reduced pressure after terminating，Add the hydrochloric acid solution of 10%，Wash three times by ethyl acetate，Obtain aqueous phase，Add ammonia regulation PH > 11，Wash 3 times by ethyl acetate，Obtain organic facies，Concentrating under reduced pressure i.e. can get crude product，Separate by column chromatography，The methylene chloride/methanol of 100:1 is eluant，Obtain sterling 1-(4-amino-2,5-diethoxy-benzyl) the bromo-phenyl of-3-(4-)-urea (300mg，80.5%)；nullReactions steps i: by 1-(4-amino-2,5-diethoxy-benzyl) the bromo-phenyl of-3-(4-)-urea (260mg，0.64mmol) add in the eggplant type bottle of 100ml，Add dichloromethane，Add pyridine (55.6mg，0.70mmol)，Carry out nitrogen protection，Add methylsufonyl chloride (73.3mg，0.64mmol)，Room temperature reaction is overnight，After reaction terminates，Hydrochloric acid solution with 10% washs three times，Obtain organic facies，Concentrating under reduced pressure i.e. can get crude product，Separate by column chromatography，The methylene chloride/methanol of 100:1 is eluant，Obtain sterling N-{4-[the bromo-phenyl of 3-(4-)-ureidomethy]-2,5-diethoxy-phenyl }-Methanesulfomide (170mg，54.8%).1H NMR (400 MHz, DMSO) δ 8.85 (s, 1H), 8.73 (s,
1H), 7.44 – 7.27 (m, 4H), 6.94 (s,
1H), 6.87 (s, 1H), 6.42 (t,J = 6.0 Hz, 1H), 4.21 (d,J = 5.6 Hz,
2H), 3.98 (q,J = 6.8 Hz, 4H), 2.92 (s, 3H), 1.32 (dd,J = 12.0,
6.4 Hz, 6H)。
Claims (6)
1. a noval chemical compound, it is characterized in that, and the entitled N-{4-of this compound [the bromo-phenyl of 3-(4-)-ureidomethy]-2,5-diethoxy-phenyl }-Methanesulfomide (compound 1), the molecular weight of this compound is 486.3, and the structural formula of this compound is shown in following formula: compound 1:
。
2. prepare noval chemical compound N-{4-[the bromo-phenyl of 3-(4-)-ureidomethy]-2 for one kind, 5-diethoxy-phenyl } method of-Methanesulfomide, it is characterized in that, show following the most totally 3 reactions steps of reactions steps g, reactions steps h, reactions steps i including following reaction scheme 1:
The condition of reactions steps g is: para-bromoaniline and compound G molar ratio range are 0.8:1 ~ 1.3:1, triethylamine and compound G mol ratio=0.8:1 ~ 5:1), solvent is N, N dimethylformamide or dimethyl sulfoxide or acetone or 1, single solvent or the combinations of solvent such as 4 dioxane, reaction temperature is 50 ~ 120 degree, and the response time is 5 ~ 18 hours, reaction is purified to obtain product compound H, yield spectra 50% ~ 90% through concentrate, extract, crystallization etc. after terminating；The condition of reactions steps h is: Nickel dichloride hexahydrate and compound H molar ratio range are 0.9:1 ~ 2.5:1, sodium borohydride and compound H molar ratio range are 0.9:1 ~ 4:1, solvent is dichloromethane or the single solvent such as oxolane or ether or the combination of solvent, response time is 10 minutes ~ 12 hours, reaction is purified to obtain product compound I, yield spectra 50% ~ 95% through extraction, crystallization etc. after terminating；The condition of reactions steps i is: alkyl sulfonyl chloride and compound I molar ratio range are 0.8:1 ~ 1.5:1, pyridine and compound I molar ratio range are 0.9:1 ~ 1.5:1, solvent is dichloromethane or oxolane or ether or N, N dimethylformamide or dimethyl sulfoxide or acetone or 1, single solvent or the combinations of solvent such as 4 dioxane, reaction temperature is 0 ~ 80 degree, 3 ~ 18 hours response time, reaction is purified to obtain product compound 1, yield spectra 50% ~ 95% through extraction, crystallization, column chromatography etc. after terminating.
3. the compound that the present invention provides has good quasi-medicated property, can be used for new drug research field and especially treats type ii diabetes field of innovative medicine research.
4. a pharmaceutical composition, including the compound described in the claim 1 of therapeutically effective amount or its pharmaceutically acceptable salt.
Pharmaceutical composition the most according to claim 4, is characterized in that, this pharmaceutical composition contains one or more pharmaceutically acceptable carrier or excipient further.
Pharmaceutical composition the most according to claim 4, is characterized in that, described compound or its pharmaceutically acceptable salt account for gross weight ratio 50% ~ 99.5% as active component.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510001141.XA CN105820071A (en) | 2015-01-05 | 2015-01-05 | N-{4-[3-(4-bromo-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-methanesulfonamide new compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510001141.XA CN105820071A (en) | 2015-01-05 | 2015-01-05 | N-{4-[3-(4-bromo-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-methanesulfonamide new compound and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105820071A true CN105820071A (en) | 2016-08-03 |
Family
ID=56986875
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510001141.XA Pending CN105820071A (en) | 2015-01-05 | 2015-01-05 | N-{4-[3-(4-bromo-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-methanesulfonamide new compound and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105820071A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106167456A (en) * | 2015-05-20 | 2016-11-30 | 齐鲁工业大学 | New Type Urea albuminoid tyrosine-phosphatase 1B inhibitor and preparation method thereof, pharmaceutical composition and purposes |
| CN106539782A (en) * | 2016-09-28 | 2017-03-29 | 齐鲁工业大学 | A kind of new 4 bromophenyl ureas adjusts the compound and its medical usage of estrogen-related receptor activity |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040037022A1 (en) * | 2000-09-25 | 2004-02-26 | Minoru Sakurai | Aminoalcohol derivatives |
| CN101142174A (en) * | 2005-03-19 | 2008-03-12 | 株式会社Amorepacific | Novel compounds, isomer thereof, or pharmaceutically acceptable salts thereof as vanilloid receptor antagonist, and pharmaceutical compositions containing the same |
-
2015
- 2015-01-05 CN CN201510001141.XA patent/CN105820071A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040037022A1 (en) * | 2000-09-25 | 2004-02-26 | Minoru Sakurai | Aminoalcohol derivatives |
| CN101142174A (en) * | 2005-03-19 | 2008-03-12 | 株式会社Amorepacific | Novel compounds, isomer thereof, or pharmaceutically acceptable salts thereof as vanilloid receptor antagonist, and pharmaceutical compositions containing the same |
Non-Patent Citations (1)
| Title |
|---|
| MARIE REILLE-SEROUSSI，ET AL: "Thienopyrimidinedione Formation Versus Ester Hydrolysis from Ureido Carboxylic Acid Methyl Ester", 《SYNTHESIS》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106167456A (en) * | 2015-05-20 | 2016-11-30 | 齐鲁工业大学 | New Type Urea albuminoid tyrosine-phosphatase 1B inhibitor and preparation method thereof, pharmaceutical composition and purposes |
| CN106539782A (en) * | 2016-09-28 | 2017-03-29 | 齐鲁工业大学 | A kind of new 4 bromophenyl ureas adjusts the compound and its medical usage of estrogen-related receptor activity |
| CN106539782B (en) * | 2016-09-28 | 2019-08-20 | 齐鲁工业大学 | A kind of 4- bromophenyl ureas adjusts the active compound of estrogen-related receptor and its medical usage |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10407403B2 (en) | Preparation method of cobimetinib | |
| US11718611B2 (en) | Benzenesulfonylbenazamide compound for inhibiting BCL-2 protein and composition and use thereof | |
| TW201118098A (en) | Processes for preparing pemetrexed | |
| CN109096219B (en) | Novel anti-PD-L1 compound, application thereof and composition containing same | |
| CN105820067A (en) | N-{[2,5-diethoxy-4-[(3-phenyl-ureido)-methyl]-phenyl}-methanesulfonamide new compound and preparation method and application thereof | |
| CN105820093A (en) | N-benzyl-5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethyoxyl benzamide new compound and preparation method and application thereof | |
| CN105820071A (en) | N-{4-[3-(4-bromo-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-methanesulfonamide new compound and preparation method and application thereof | |
| JP2017502039A (en) | Methods and reagents for radiolabeling | |
| CN105820094A (en) | 4-methoxy-benzyl-based substituted benzamide new compound, preparation method and application | |
| CN105820087A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-p-methylphenyl-benzamide new compound and preparation method and application thereof | |
| CN105820085A (en) | Ethanesulfonic acid{4-[3-(3-bromo-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-amide new compound, preparation method and application | |
| CN105820090A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-(3-methoxy-phenyl)-benzamide new compound and preparation method and application thereof | |
| CN105820078A (en) | 2-benzyloxy-5-[3-(2,5-diethoxy-4-methanesulfonyl-benzyl)-ureido]- methyl benzoate new compound and preparation method and application thereof | |
| CN105820069A (en) | N-{4-[3-(3-bromo-phenyl)-ureidomethyl]-2,5-dibutoxy-phenyl}-methanesulfonamide new compound and preparation method and application thereof | |
| CN105820083A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-phenyl-benzamide new compound and preparation method and application thereof | |
| CN105820082A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-isopropyl-benzamide new compound and preparation method and application thereof | |
| CN105820077A (en) | 2-butoxyl-5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-methyl benzoate new compound and preparation method and application thereof | |
| CN105820074A (en) | N-[4-(3-benzyl-ureidomethyl)-2,5-diethoxyphenyl]methanesulfonamide new compound and preparation method and application thereof | |
| CN105820068A (en) | N-{4-[3-(3-bromo-phenyl)-ureidomethyl]-2,5-dipropoxy-phenyl}-methanesulfonamide new compound and preparation method and application thereof | |
| CN105820076A (en) | N-[2,5-diethoxy-4-(3-p-tolyl-ureidomethyl)-phenyl]-methanesulfonamide new compound and preparation method and application thereof | |
| CN105820073A (en) | N-{[2,5-diethoxy-4-[(3-phenyl-ureido)-methyl]-phenyl}-methanesulfonamide new compound and preparation method and application thereof | |
| CN105820072A (en) | N-{[2,5-diethoxy-4-[3-(4-methoxy-phenyl)-ureidomethyl]-phenyl}-methanesulfonamide new compound and preparation method and application thereof | |
| CN105820075A (en) | N-{4-[3-(3,4-dimethoxy-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-methanesulfonamide new compound and preparation method and application thereof | |
| CN105820080A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-ethyl-benzamide new compound and preparation method and application thereof | |
| CN105820084A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-propoxy-methyl benzoate new compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160803 |