JP2018501315A5 - - Google Patents
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- JP2018501315A5 JP2018501315A5 JP2017552007A JP2017552007A JP2018501315A5 JP 2018501315 A5 JP2018501315 A5 JP 2018501315A5 JP 2017552007 A JP2017552007 A JP 2017552007A JP 2017552007 A JP2017552007 A JP 2017552007A JP 2018501315 A5 JP2018501315 A5 JP 2018501315A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- hydrogen
- pyridin
- halogen
- independently
- 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
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- 229910052739 hydrogen Inorganic materials 0.000 claims 109
- 239000001257 hydrogen Substances 0.000 claims 109
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 54
- 125000004093 cyano group Chemical group *C#N 0.000 claims 48
- 229910052736 halogen Inorganic materials 0.000 claims 48
- 150000002367 halogens Chemical group 0.000 claims 48
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 43
- 150000002431 hydrogen Chemical group 0.000 claims 39
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 36
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 23
- 150000003839 salts Chemical class 0.000 claims 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 16
- 150000001875 compounds Chemical class 0.000 claims 15
- -1 —OH Chemical group 0.000 claims 12
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 11
- 125000000623 heterocyclic group Chemical group 0.000 claims 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 9
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 9
- 125000000217 alkyl group Chemical group 0.000 claims 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 8
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 8
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 8
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 7
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 5
- 239000005557 antagonist Substances 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 102000052185 transforming growth factor beta receptor activity proteins Human genes 0.000 claims 4
- 108700015056 transforming growth factor beta receptor activity proteins Proteins 0.000 claims 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- XODSKPZUYKGNMW-UHFFFAOYSA-N N-[4-[3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound COC1=CC=C(C=N1)C1=C(NC=2C1=NC=CC=2)C1=CC(=NC=C1)NC(C)=O XODSKPZUYKGNMW-UHFFFAOYSA-N 0.000 claims 1
- VWSFKHLXKXHRDY-UHFFFAOYSA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=CC=2)C1=CC(=NC=C1)NC(C)=O)F VWSFKHLXKXHRDY-UHFFFAOYSA-N 0.000 claims 1
- LZIKYNOAPPEQMG-UHFFFAOYSA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-6-ethoxy-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=C(C=2)OCC)C1=CC(=NC=C1)NC(C)=O)F LZIKYNOAPPEQMG-UHFFFAOYSA-N 0.000 claims 1
- YAURUPNGLRUZTR-UHFFFAOYSA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-6-methoxy-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=C(C=2)OC)C1=CC(=NC=C1)NC(C)=O)F YAURUPNGLRUZTR-UHFFFAOYSA-N 0.000 claims 1
- OLYCUNOTKFNETC-UHFFFAOYSA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-7-(1-hydroxyethyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=CC=2C(C)O)C1=CC(=NC=C1)NC(C)=O)F OLYCUNOTKFNETC-UHFFFAOYSA-N 0.000 claims 1
- BXHURORUSAJJMH-UHFFFAOYSA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-7-(2-hydroxypropan-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=CC=2C(C)(C)O)C1=CC(=NC=C1)NC(C)=O)F BXHURORUSAJJMH-UHFFFAOYSA-N 0.000 claims 1
- CDVFGEXFOAGXJO-UHFFFAOYSA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-7-(methylaminomethyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=CC=2CNC)C1=CC(=NC=C1)NC(C)=O)F CDVFGEXFOAGXJO-UHFFFAOYSA-N 0.000 claims 1
- OLYCUNOTKFNETC-LLVKDONJSA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-7-[(1R)-1-hydroxyethyl]-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=CC=2[C@@H](C)O)C1=CC(=NC=C1)NC(C)=O)F OLYCUNOTKFNETC-LLVKDONJSA-N 0.000 claims 1
- OLYCUNOTKFNETC-NSHDSACASA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-7-[(1S)-1-hydroxyethyl]-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=CC=2[C@H](C)O)C1=CC(=NC=C1)NC(C)=O)F OLYCUNOTKFNETC-NSHDSACASA-N 0.000 claims 1
- AQUKDYPRJZEQSG-UHFFFAOYSA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-7-[(dimethylamino)methyl]-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=CC=2CN(C)C)C1=CC(=NC=C1)NC(C)=O)F AQUKDYPRJZEQSG-UHFFFAOYSA-N 0.000 claims 1
- UKJWABCHVCNLAX-UHFFFAOYSA-N N-[4-[3-[6-(difluoromethyl)pyridin-2-yl]-7-ethoxy-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC(C1=CC=CC(=N1)C1=C(NC=2C1=NC=CC=2OCC)C1=CC(=NC=C1)NC(C)=O)F UKJWABCHVCNLAX-UHFFFAOYSA-N 0.000 claims 1
- KBCCSSMKVXTFDE-UHFFFAOYSA-N N-[4-[6-chloro-3-(5-fluoropyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]-2-(3-morpholin-4-ylpropylamino)acetamide Chemical compound ClC=1C=C2C(=NC=1)C(=C(N2)C1=CC(=NC=C1)NC(CNCCCN1CCOCC1)=O)C1=NC=C(C=C1)F KBCCSSMKVXTFDE-UHFFFAOYSA-N 0.000 claims 1
- SDIWHZMLILEDAK-UHFFFAOYSA-N N-[4-[6-chloro-3-(5-methoxypyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound ClC=1C=C2C(=NC=1)C(=C(N2)C1=CC(=NC=C1)NC(C)=O)C1=NC=C(C=C1)OC SDIWHZMLILEDAK-UHFFFAOYSA-N 0.000 claims 1
- SDIWHZMLILEDAK-BMSJAHLVSA-N N-[4-[6-chloro-3-[5-(trideuteriomethoxy)pyridin-2-yl]-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound ClC=1C=C2C(=NC=1)C(=C(N2)C1=CC(=NC=C1)NC(C)=O)C1=NC=C(C=C1)OC([2H])([2H])[2H] SDIWHZMLILEDAK-BMSJAHLVSA-N 0.000 claims 1
- MCOHDLNMMNXGOH-UHFFFAOYSA-N N-[4-[6-fluoro-3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC=1C=C2C(=NC=1)C(=C(N2)C1=CC(=NC=C1)NC(C)=O)C=1C=NC(=CC=1)OC MCOHDLNMMNXGOH-UHFFFAOYSA-N 0.000 claims 1
- TWGKOZPGDCIKQA-BMSJAHLVSA-N N-[4-[6-fluoro-3-[5-(trideuteriomethoxy)pyridin-2-yl]-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound FC=1C=C2C(=NC=1)C(=C(N2)C1=CC(=NC=C1)NC(C)=O)C1=NC=C(C=C1)OC([2H])([2H])[2H] TWGKOZPGDCIKQA-BMSJAHLVSA-N 0.000 claims 1
- PRIWSHXIEAISOK-UHFFFAOYSA-N N-[4-[6-methoxy-3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound COC=1C=C2C(=NC=1)C(=C(N2)C1=CC(=NC=C1)NC(C)=O)C=1C=NC(=CC=1)OC PRIWSHXIEAISOK-UHFFFAOYSA-N 0.000 claims 1
- OUXSSNKXGXEJMO-BMSJAHLVSA-N N-[4-[6-methoxy-3-[5-(trideuteriomethoxy)pyridin-2-yl]-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound [2H]C([2H])([2H])OC1=CN=C(C=C1)C1=C(NC2=C1N=CC(OC)=C2)C1=CC(NC(C)=O)=NC=C1 OUXSSNKXGXEJMO-BMSJAHLVSA-N 0.000 claims 1
- IHDQOIQCCCQCNA-UHFFFAOYSA-N N-[4-[7-(1-hydroxyethyl)-3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl]acetamide Chemical compound OC(C)C1=C2C(=NC=C1)C(=C(N2)C1=CC(=NC=C1)NC(C)=O)C=1C=NC(=CC=1)OC IHDQOIQCCCQCNA-UHFFFAOYSA-N 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 206010041067 Small cell lung cancer Diseases 0.000 claims 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims 1
- 201000011176 T-cell adult acute lymphocytic leukemia Diseases 0.000 claims 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims 1
- 229930192474 thiophene Chemical group 0.000 claims 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462095328P | 2014-12-22 | 2014-12-22 | |
| US62/095,328 | 2014-12-22 | ||
| PCT/US2015/067252 WO2016106266A1 (en) | 2014-12-22 | 2015-12-22 | TGFβ RECEPTOR ANTAGONISTS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2018501315A JP2018501315A (ja) | 2018-01-18 |
| JP2018501315A5 true JP2018501315A5 (enExample) | 2019-01-24 |
Family
ID=55135542
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017552007A Pending JP2018501315A (ja) | 2014-12-22 | 2015-12-22 | ＴＧＦβ受容体アンタゴニスト |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9708316B2 (enExample) |
| EP (1) | EP3237415A1 (enExample) |
| JP (1) | JP2018501315A (enExample) |
| CN (1) | CN107257798A (enExample) |
| AR (1) | AR103232A1 (enExample) |
| TW (1) | TW201630907A (enExample) |
| WO (1) | WO2016106266A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
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| LT3089971T (lt) | 2014-01-01 | 2020-10-12 | Medivation Technologies Llc | Junginiai ir panaudojimo būdai |
| JP2019534266A (ja) * | 2016-10-14 | 2019-11-28 | 江蘇恒瑞医薬股▲ふん▼有限公司 | ５員ヘテロアリール環の架橋した環誘導体、その製造方法およびその医学的使用 |
| CA3043383A1 (en) | 2016-11-14 | 2018-05-17 | Jiangsu Hengrui Medicine Co., Ltd. | 3,4-bipyridyl pyrazole derivative, and preparation method therefor and medical application thereof |
| WO2018171611A1 (zh) * | 2017-03-22 | 2018-09-27 | 江苏恒瑞医药股份有限公司 | 6-吡唑-[1,2,4]三唑并[4,3-a]吡啶-3-酰胺类衍生物、其制备方法及其在医药上的应用 |
| US10428067B2 (en) | 2017-06-07 | 2019-10-01 | Plexxikon Inc. | Compounds and methods for kinase modulation |
| BR112020011771A2 (pt) | 2017-12-18 | 2020-11-17 | Bristol-Myers Squibb Company | compostos 4-azaindol |
| FI3796975T3 (fi) | 2018-05-22 | 2023-11-20 | Orsobio Inc | Sulfonyyliaminobentsamidijohdannaisia |
| TWI748194B (zh) | 2018-06-28 | 2021-12-01 | 德商菲尼克斯 Ｆｘｒ有限責任公司 | 含有雙環核心部分之新穎lxr調節劑 |
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| CN112694477B (zh) * | 2019-10-22 | 2024-02-06 | 四川科伦博泰生物医药股份有限公司 | 吡唑并环类化合物，包含其的药物组合物，其制备方法及其用途 |
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| EP4469457A1 (en) * | 2022-01-27 | 2024-12-04 | The Broad Institute Inc. | Substituted heterocyclic csnk1 inhibitors |
| EP4476223A1 (en) * | 2022-02-07 | 2024-12-18 | Cornell University | Inhibitors of malic enzyme 1 |
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| RU2617966C2 (ru) | 2010-03-05 | 2017-04-28 | Ф.Хоффманн-Ля Рош Аг | Антитела против csf-1r человека и их применение |
| KR101656548B1 (ko) | 2010-03-05 | 2016-09-09 | 에프. 호프만-라 로슈 아게 | 인간 ｃｓｆ-1ｒ에 대한 항체 및 이의 용도 |
| KR20200044999A (ko) | 2010-05-04 | 2020-04-29 | 파이브 프라임 테라퓨틱스, 인크. | Ｃｓｆ1ｒ에 결합하는 항체들 |
| CN105481983B (zh) | 2010-09-09 | 2021-09-03 | 辉瑞公司 | 4-1bb结合分子 |
| NO2694640T3 (enExample) | 2011-04-15 | 2018-03-17 | ||
| MX338353B (es) | 2011-04-20 | 2016-04-13 | Medimmune Llc | Anticuerpos y otras moleculas que se unen a b7 - h1 y pd - 1. |
| SMT202000561T1 (it) | 2011-11-28 | 2021-01-05 | Merck Patent Gmbh | Anticorpi anti-pd-l1 e usi relativi |
| MX356337B (es) | 2011-12-15 | 2018-05-23 | Hoffmann La Roche | Anticuerpos contra csf-1r humano y sus usos. |
| JP6416630B2 (ja) | 2012-02-06 | 2018-10-31 | ジェネンテック， インコーポレイテッド | Ｃｓｆ１ｒ阻害剤を用いるための組成物及び方法 |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| EP2847220A1 (en) | 2012-05-11 | 2015-03-18 | Five Prime Therapeutics, Inc. | Methods of treating conditions with antibodies that bind colony stimulating factor 1 receptor (csf1r) |
| UY34887A (es) | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
| TWI713436B (zh) | 2012-08-31 | 2020-12-21 | 美商戊瑞治療有限公司 | 用結合群落刺激因子１受體（ｃｓｆ１ｒ）之抗體治療病狀之方法 |
| GB201304527D0 (en) * | 2013-03-13 | 2013-04-24 | Proximagen Ltd | New compounds |
-
2015
- 2015-12-21 AR ARP150104241A patent/AR103232A1/es unknown
- 2015-12-21 TW TW104142991A patent/TW201630907A/zh unknown
- 2015-12-22 WO PCT/US2015/067252 patent/WO2016106266A1/en not_active Ceased
- 2015-12-22 US US14/977,709 patent/US9708316B2/en active Active
- 2015-12-22 EP EP15823892.3A patent/EP3237415A1/en not_active Withdrawn
- 2015-12-22 JP JP2017552007A patent/JP2018501315A/ja active Pending
- 2015-12-22 CN CN201580076649.4A patent/CN107257798A/zh active Pending
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