CN105820079A - 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-methyl-benzamide new compound and preparation method and application thereof - Google Patents
5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-methyl-benzamide new compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN105820079A CN105820079A CN201510001270.9A CN201510001270A CN105820079A CN 105820079 A CN105820079 A CN 105820079A CN 201510001270 A CN201510001270 A CN 201510001270A CN 105820079 A CN105820079 A CN 105820079A
- Authority
- CN
- China
- Prior art keywords
- compound
- reactions steps
- solvent
- diethoxy
- benzyl
- 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)
Abstract
The invention provides a new compound. The name of the compound is 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-methyl-benzamide; molecular weight of the compound is 508.5; 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 5-[3-(2 of offer; 5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups]-2-ethyoxyl-N-methyl-benzamide 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 5-[3-(2; 5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups]-2-ethyoxyl-N-methyl-benzamide 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; entitled 5-[the 3-(2 of this compound; 5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups]-2-ethyoxyl-N-methyl-benzamide (compound 1); the molecular weight of this compound is 508.5, and the structural formula of this compound is shown in following formula: compound 1:
2, one prepares noval chemical compound 5-[3-(2; 5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups] method of-2-ethyoxyl-N-methyl-benzamide; it is characterized in that; including reactions steps g4 shown in following reaction scheme 1, reactions steps g5, reactions steps g6, reactions steps g7, reactions steps g8, reactions steps g, reactions steps h, following totally 8 reactions steps of reactions steps i, the condition flag that wherein reactions steps g, reactions steps h, this 3 step of reactions steps i are reacted is as follows:
The condition of reactions steps g is: 2,5-diethoxy-4-Nitro-benzyl amine 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 single solvent or the combination of solvent such as acetone or Isosorbide-5-Nitrae dioxane, reaction temperature is 50 ~ 120 degree, response time is 5 ~ 18 hours, and 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
The structural formula of embodiment 1:5-[3-(2,5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups]-2-ethyoxyl-N-methyl-benzamide (compound 1) is as follows:
The synthetic route of compound 5-[3-(2,5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups]-2-ethyoxyl-N-methyl-benzamide is as follows:
Compound 5-[3-(2, 5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups] the concrete preparation method of-2-ethyoxyl-N-methyl-benzamide is as follows: the preparation of reactions steps g4(compound G1-4): by (compound G1-3) 2-ethyoxyl-5-Nitro-benzoic acid methyl ester (6g, 26.7mmol) add in 250ml eggplant-shape bottle, add 150ml water, it is heated to 60-80 DEG C, add potassium hydroxide (3g, 53.6mmol), reaction 4-6h, reaction adds hydrochloric acid regulation PH < 3 after terminating, white crystal is had to separate out, decompression sucking filtration i.e. can get sterling 2-ethyoxyl-5-Nitro-benzoic acid (5.5g, 97.7%)；The preparation of reactions steps g5(compound G1-5): by 2-ethyoxyl-5-Nitro-benzoic acid (5.5g, 26.1mmol) add in the eggplant type bottle of 250ml, add 150ml dichloromethane, add thionyl chloride (6.2g, 52.1mmol), add 1 DMF, room temperature reaction 6-8h, after reaction terminates, carrying out concentrating under reduced pressure, repeatedly dichloromethane carries out concentrating under reduced pressure.Obtain 2-ethyoxyl-5-nitro-benzoyl chloride (5.9g, 98.6%)；The preparation of reactions steps g6(compound G1-6): by 2-ethyoxyl-5-nitro-benzoyl chloride (500mg, 2.18mmol) add in 100ml eggplant type bottle, add dichloromethane to be completely dissolved, add methylamine (67.5mg, 2.18mmol), add triethylamine (242mg, 2.40mmol), room temperature reaction 0.5-2h, reaction terminates to wash three times with the hydrochloric acid solution of 10%, is concentrated under reduced pressure to give crude product, use column chromatography sharp separation, with dichloromethane eluent, obtain sterling 2-ethyoxyl-N-methyl-5-nitro-Benzoylamide (430mg, 88.1%)；nullThe preparation of reactions steps g7(compound G1-7): by 2-ethyoxyl-N-methyl-5-nitro-Benzoylamide (400mg，1.79mmol) add in 100ml eggplant type bottle and add methanol，Add Nickel dichloride hexahydrate (729mg，3.06mmol)，After being completely dissolved，Add sodium borohydride (233mg，6.14mmol)，React 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 5-amino-2-ethyoxyl-N-methyl-benzamide (330mg，95.4%)；The preparation of reactions steps g8(compound G1-8): by phenyl chloroformate (224mg; 1.43mmol) add in the eggplant type bottle of 100ml; add dichloromethane; add 5-amino-2-ethyoxyl-N-methyl-benzamide (320mg; 1.43mmol) with triethylamine (159mg; 1.57mmol); room temperature reaction 0.5-2h; reaction is washed 3 times with the hydrochloric acid solution of 10% after terminating; it is concentrated under reduced pressure to give crude product; carry out recrystallization with ethanol and can get sterling (4-ethyoxyl-3-methylcarbamoyl-phenyl)-phenyl carbamate (450mg, productivity 86.9%)；The preparation of reactions steps g(compound H): by 2, 5-diethoxy-4-Nitro-benzyl amine (300mg, 1.25mmol), (4-ethyoxyl-3-methylcarbamoyl-phenyl)-phenyl carbamate (393mg, 1.25mmol) with triethylamine (1.26g, 12.5mmol) 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 sterling 5-[3-(2, 5-diethoxy-4-Nitro-benzyl)-urea groups]-2-ethyoxyl-N-methyl-benzamide (475mg, productivity 82.6%)；nullThe preparation of reactions steps h(compound I): by 5-[3-(2,5-diethoxy-4-Nitro-benzyl)-urea groups]-2-ethyoxyl-N-methyl-benzamide (460mg,1.0mmol) add in the eggplant type bottle of 100ml，Add methanol，Add Nickel dichloride hexahydrate (408mg，1.71mmol)，After being completely dissolved，Add sodium borohydride (130.0mg，3.43mmol)，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 5-[3-(4-amino-2,5-diethoxy-benzyl)-urea groups]-2-ethyoxyl-N-methyl-benzamide (360mg，83.7%)；nullThe preparation of reactions steps i(compound 1): by 5-[3-(4-amino-2,5-diethoxy-benzyl)-urea groups]-2-ethyoxyl-N-methyl-benzamide (300mg，0.70mmol) add in the eggplant type bottle of 100ml，Add dichloromethane，Add pyridine (60.8mg，0.77mmol)，Carry out nitrogen protection，Add methylsufonyl chloride (80.2mg，0.70mmol)，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 5-[3-(2,5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups]-2-ethyoxyl-N-methyl-benzamide (170mg，47.9%).1HNMR(400MHz,DMSO)δ8.81(s,1H),8.54(s,1H),8.06(d,J=4.4Hz,1H),7.70(d,J=2.8Hz,1H),7.54(dd,J=8.6,3.0Hz,1H),7.00(d,J=8.8Hz,1H),6.94(s,1H),6.87(s,1H),6.26(t,J=6.2Hz,1H),4.21(d,J=5.6Hz,2H),4.09(q,J=6.8Hz,2H),3.99(m,4H),2.93(s,3H),2.79(d,J=4.8Hz,3H),1.33(m,9H)。
Claims (6)
1. a noval chemical compound; it is characterized in that; entitled 5-[the 3-(2 of this compound; 5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups]-2-ethyoxyl-N-methyl-benzamide (compound 1); the molecular weight of this compound is 508.5, and the structural formula of this compound is shown in following formula: compound 1.
2. prepare noval chemical compound 5-[3-(2 for one kind; 5-diethoxy-4-Methanesulfonyl-benzYl)-urea groups] method of-2-ethyoxyl-N-methyl-benzamide; it is characterized in that; including reactions steps g4 shown in following reaction scheme 1, reactions steps g5, reactions steps g6, reactions steps g7, reactions steps g8, reactions steps g, reactions steps h, following totally 8 reactions steps of reactions steps i, the condition flag that wherein reactions steps g, reactions steps h, this 3 step of reactions steps i are reacted is as follows:
The condition of reactions steps g is: 2,5-diethoxy-4-Nitro-benzyl amine 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 single solvent or the combination of solvent such as acetone or Isosorbide-5-Nitrae dioxane, reaction temperature is 50 ~ 120 degree, response time is 5 ~ 18 hours, and 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 |
|---|---|---|---|
| CN201510001270.9A CN105820079A (en) | 2015-01-05 | 2015-01-05 | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-methyl-benzamide new compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510001270.9A CN105820079A (en) | 2015-01-05 | 2015-01-05 | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-methyl-benzamide new compound and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105820079A true CN105820079A (en) | 2016-08-03 |
Family
ID=56986865
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510001270.9A Pending CN105820079A (en) | 2015-01-05 | 2015-01-05 | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-methyl-benzamide new compound and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105820079A (en) |
Cited By (1)
| 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 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1418191A (en) * | 2000-08-21 | 2003-05-14 | 株式会社太平洋 | Novel thiourea derivatives and the pharmaceutical compositions containing thd same |
| US20040259912A1 (en) * | 2001-09-28 | 2004-12-23 | Takahiro Matsumoto | Benzine derivatives, process for preparing the same and use thereof |
| 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 |
| CN101516361A (en) * | 2006-09-28 | 2009-08-26 | 亚瑞特医疗公司 | Soluble epoxide hydrolase inhibitors |
| WO2010146236A1 (en) * | 2009-06-16 | 2010-12-23 | Biotie Therapies Corp. | Urea substituted sulphonamide derivatives |
-
2015
- 2015-01-05 CN CN201510001270.9A patent/CN105820079A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1418191A (en) * | 2000-08-21 | 2003-05-14 | 株式会社太平洋 | Novel thiourea derivatives and the pharmaceutical compositions containing thd same |
| US20040259912A1 (en) * | 2001-09-28 | 2004-12-23 | Takahiro Matsumoto | Benzine derivatives, process for preparing the same and use thereof |
| 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 |
| CN101163670A (en) * | 2005-03-19 | 2008-04-16 | 株式会社太平洋 | Novel compounds, isomer thereof, or pharmaceutically acceptable salts thereof as vanilloid receptor antagonist, and pharmaceutical compositions containing the same |
| CN101516361A (en) * | 2006-09-28 | 2009-08-26 | 亚瑞特医疗公司 | Soluble epoxide hydrolase inhibitors |
| WO2010146236A1 (en) * | 2009-06-16 | 2010-12-23 | Biotie Therapies Corp. | Urea substituted sulphonamide derivatives |
Non-Patent Citations (1)
| Title |
|---|
| "Oligoamide Duplexes as Organogelators";Cao Ruikaiet al.;《Organic Letters》;20100610;第12卷;Supporting Information, S15-17 * |
Cited By (1)
| 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 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2602260B1 (en) | Process for preparing compound having hiv integrase inhibitory activity | |
| CN103274961A (en) | Compositions and methods of treating cell proliferation disorders | |
| JPS58154582A (en) | Novel camptothecin derivative and its preparation | |
| CN107365275B (en) | High purity celecoxib | |
| TW201118098A (en) | Processes for preparing pemetrexed | |
| US20180251461A1 (en) | Methods and reagents for radiolabeling | |
| WO2010037210A1 (en) | Viral polymerase inhibitors | |
| CN108794412B (en) | Preparation method of 4, 5-diaryl-2H-1, 2, 3-triazole compound | |
| CN105820093A (en) | N-benzyl-5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethyoxyl benzamide new compound and preparation method and application thereof | |
| CN105820094A (en) | 4-methoxy-benzyl-based substituted benzamide new compound, preparation method and application | |
| CN105820067A (en) | N-{[2,5-diethoxy-4-[(3-phenyl-ureido)-methyl]-phenyl}-methanesulfonamide new compound and preparation method and application thereof | |
| CN105820079A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-methyl-benzamide new compound and preparation method and application thereof | |
| 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 | |
| CN105820077A (en) | 2-butoxyl-5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-methyl benzoate new compound and preparation method and application thereof | |
| 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 | |
| CN105820082A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-isopropyl-benzamide 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 | |
| CN105820078A (en) | 2-benzyloxy-5-[3-(2,5-diethoxy-4-methanesulfonyl-benzyl)-ureido]- methyl benzoate 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 | |
| CN105820071A (en) | N-{4-[3-(4-bromo-phenyl)-ureidomethyl]-2,5-diethoxy-phenyl}-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 | |
| CN105820080A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-ethyl-benzamide 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 | |
| CN105820081A (en) | 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-propyl-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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160803 |
|
| RJ01 | Rejection of invention patent application after publication |