JP6453845B2 - Brd4阻害薬としてのジヒドロキナゾリノン類似体 - Google Patents
Brd4阻害薬としてのジヒドロキナゾリノン類似体 Download PDFInfo
- Publication number
- JP6453845B2 JP6453845B2 JP2016504661A JP2016504661A JP6453845B2 JP 6453845 B2 JP6453845 B2 JP 6453845B2 JP 2016504661 A JP2016504661 A JP 2016504661A JP 2016504661 A JP2016504661 A JP 2016504661A JP 6453845 B2 JP6453845 B2 JP 6453845B2
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- methyl
- mmol
- mixture
- hplc
- 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.)
- Active
Links
- 0 C1Cc2ccccc2*C1 Chemical compound C1Cc2ccccc2*C1 0.000 description 7
- LBUJPTNKIBCYBY-UHFFFAOYSA-N C(C1)CNc2c1cccc2 Chemical compound C(C1)CNc2c1cccc2 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 1
- SGLTYXRTDQXURA-UHFFFAOYSA-N C(CNC1)C11CNCCC1 Chemical compound C(CNC1)C11CNCCC1 SGLTYXRTDQXURA-UHFFFAOYSA-N 0.000 description 1
- ZMSGYKXUAZKXHT-QQTPKPIZSA-N C/C=C\C=C(\CCS(C1)=O)/C1=C Chemical compound C/C=C\C=C(\CCS(C1)=O)/C1=C ZMSGYKXUAZKXHT-QQTPKPIZSA-N 0.000 description 1
- NATSLBVLBWGPRZ-UDJLOATDSA-N C/C=C\C=C1\OCOC1 Chemical compound C/C=C\C=C1\OCOC1 NATSLBVLBWGPRZ-UDJLOATDSA-N 0.000 description 1
- ZQGLEEFGEZLSAJ-UHFFFAOYSA-N C1COC2(CCNCC2)OC1 Chemical compound C1COC2(CCNCC2)OC1 ZQGLEEFGEZLSAJ-UHFFFAOYSA-N 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N C1NCc2ccccc12 Chemical compound C1NCc2ccccc12 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- MXMZCLLIUQEKSN-UHFFFAOYSA-N C1Nc2ccccc2N1 Chemical compound C1Nc2ccccc2N1 MXMZCLLIUQEKSN-UHFFFAOYSA-N 0.000 description 1
- YBBLSBDJIKMXNQ-UHFFFAOYSA-N C1Nc2ccccc2SC1 Chemical compound C1Nc2ccccc2SC1 YBBLSBDJIKMXNQ-UHFFFAOYSA-N 0.000 description 1
- NHSOOAWURRKYMM-UHFFFAOYSA-N C1Oc(cccc2)c2SC1 Chemical compound C1Oc(cccc2)c2SC1 NHSOOAWURRKYMM-UHFFFAOYSA-N 0.000 description 1
- HRCMXYXVAWHBTH-UHFFFAOYSA-N C1Oc2ccccc2N1 Chemical compound C1Oc2ccccc2N1 HRCMXYXVAWHBTH-UHFFFAOYSA-N 0.000 description 1
- BNBQRQQYDMDJAH-UHFFFAOYSA-N C1Oc2ccccc2OC1 Chemical compound C1Oc2ccccc2OC1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
- KVRZARWOKBNZMM-UHFFFAOYSA-N C1SCc2c1cccc2 Chemical compound C1SCc2c1cccc2 KVRZARWOKBNZMM-UHFFFAOYSA-N 0.000 description 1
- WOHLSTOWRAOMSG-UHFFFAOYSA-N C1Sc(cccc2)c2N1 Chemical compound C1Sc(cccc2)c2N1 WOHLSTOWRAOMSG-UHFFFAOYSA-N 0.000 description 1
- AIUOUEPKBRDPLG-UHFFFAOYSA-N C1Sc(cccc2)c2O1 Chemical compound C1Sc(cccc2)c2O1 AIUOUEPKBRDPLG-UHFFFAOYSA-N 0.000 description 1
- HCMLNPZTRYNCMA-UHFFFAOYSA-N C1Sc2ccccc2S1 Chemical compound C1Sc2ccccc2S1 HCMLNPZTRYNCMA-UHFFFAOYSA-N 0.000 description 1
- VIDHILKLKOQXEB-UHFFFAOYSA-N C1Sc2ccccc2SC1 Chemical compound C1Sc2ccccc2SC1 VIDHILKLKOQXEB-UHFFFAOYSA-N 0.000 description 1
- DQHKXDISHZSNDZ-UHFFFAOYSA-N C1c2ccccc2C=[O]C1 Chemical compound C1c2ccccc2C=[O]C1 DQHKXDISHZSNDZ-UHFFFAOYSA-N 0.000 description 1
- UWYZHKAOTLEWKK-UHFFFAOYSA-N C1c2ccccc2CNC1 Chemical compound C1c2ccccc2CNC1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 1
- ZZQUQFZVCJWSER-UHFFFAOYSA-N C1c2ccccc2CSC1 Chemical compound C1c2ccccc2CSC1 ZZQUQFZVCJWSER-UHFFFAOYSA-N 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N C1c2ccccc2NC1 Chemical compound C1c2ccccc2NC1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- JCIDEANDDNSHQC-UHFFFAOYSA-N C1c2ccccc2OC=C1 Chemical compound C1c2ccccc2OC=C1 JCIDEANDDNSHQC-UHFFFAOYSA-N 0.000 description 1
- YJUFGFXVASPYFQ-UHFFFAOYSA-N C1c2ccccc2SC1 Chemical compound C1c2ccccc2SC1 YJUFGFXVASPYFQ-UHFFFAOYSA-N 0.000 description 1
- JUCZLAZPLFDCMQ-VXLWULRPSA-N CC(C)(C)[S@@](N(C)C(c1ccccc1)c1cc(Br)ccc1N)=O Chemical compound CC(C)(C)[S@@](N(C)C(c1ccccc1)c1cc(Br)ccc1N)=O JUCZLAZPLFDCMQ-VXLWULRPSA-N 0.000 description 1
- NZXRVFKGECOPRH-UHFFFAOYSA-N CN(C(c1ccccc1)c(c(OC)ccc1)c1N1Cc(cc2)ccc2OC)C1=O Chemical compound CN(C(c1ccccc1)c(c(OC)ccc1)c1N1Cc(cc2)ccc2OC)C1=O NZXRVFKGECOPRH-UHFFFAOYSA-N 0.000 description 1
- GJDUOPXAEYSAME-UHFFFAOYSA-N CS(CCC1)(C2C1=CC=CC2)=O Chemical compound CS(CCC1)(C2C1=CC=CC2)=O GJDUOPXAEYSAME-UHFFFAOYSA-N 0.000 description 1
- KGPSRYMSHRHPMF-UHFFFAOYSA-N CS1(C)c2ccccc2OCC1 Chemical compound CS1(C)c2ccccc2OCC1 KGPSRYMSHRHPMF-UHFFFAOYSA-N 0.000 description 1
- LWKPCHOTVDJWMH-UHFFFAOYSA-N Cc([o]nc1OC)c1-c(cc1)cc(C(c2ccccc2)N2C)c1NC2=O Chemical compound Cc([o]nc1OC)c1-c(cc1)cc(C(c2ccccc2)N2C)c1NC2=O LWKPCHOTVDJWMH-UHFFFAOYSA-N 0.000 description 1
- SLBFOXCUQSFZOQ-UHFFFAOYSA-N Cc1n[o]c(C)c1-c(cc1C(c2ccccc2)N2C)ccc1N(C)C2=O Chemical compound Cc1n[o]c(C)c1-c(cc1C(c2ccccc2)N2C)ccc1N(C)C2=O SLBFOXCUQSFZOQ-UHFFFAOYSA-N 0.000 description 1
- SGYYJSPRYJQCGC-UHFFFAOYSA-N Cc1n[o]c(C)c1-c(cc1C(c2ccccc2)N2C)ccc1OC2=O Chemical compound Cc1n[o]c(C)c1-c(cc1C(c2ccccc2)N2C)ccc1OC2=O SGYYJSPRYJQCGC-UHFFFAOYSA-N 0.000 description 1
- STLHMQCWICHDHV-UHFFFAOYSA-N Cc1n[o]c(COc2c3C(c4ccccc4)N4C)c1-c2ccc3NC4=O Chemical compound Cc1n[o]c(COc2c3C(c4ccccc4)N4C)c1-c2ccc3NC4=O STLHMQCWICHDHV-UHFFFAOYSA-N 0.000 description 1
- AOBWJWZRHVWNAN-UHFFFAOYSA-N O=S1(CC2=CC=CC=CC2CC1)=O Chemical compound O=S1(CC2=CC=CC=CC2CC1)=O AOBWJWZRHVWNAN-UHFFFAOYSA-N 0.000 description 1
- JNUQDPXTKWZWFG-UHFFFAOYSA-N O=S1(c2ccccc2NC1)=O Chemical compound O=S1(c2ccccc2NC1)=O JNUQDPXTKWZWFG-UHFFFAOYSA-N 0.000 description 1
- YQADUHCTMXJQLP-UHFFFAOYSA-N O=S1c(cccc2)c2OC1 Chemical compound O=S1c(cccc2)c2OC1 YQADUHCTMXJQLP-UHFFFAOYSA-N 0.000 description 1
- CJZFOZAQGBLEFL-UHFFFAOYSA-N O=S1c2ccccc2CCC1 Chemical compound O=S1c2ccccc2CCC1 CJZFOZAQGBLEFL-UHFFFAOYSA-N 0.000 description 1
- YVAIFZYQODGYQY-UHFFFAOYSA-N O=S1c2ccccc2NC1 Chemical compound O=S1c2ccccc2NC1 YVAIFZYQODGYQY-UHFFFAOYSA-N 0.000 description 1
- ANRVBXAHQOMRFK-UHFFFAOYSA-N O=S1c2ccccc2NCC1 Chemical compound O=S1c2ccccc2NCC1 ANRVBXAHQOMRFK-UHFFFAOYSA-N 0.000 description 1
- UHQHELVMFUPEHC-UHFFFAOYSA-O O[S@@+](CC1)(c2ccccc2S1=O)=O Chemical compound O[S@@+](CC1)(c2ccccc2S1=O)=O UHQHELVMFUPEHC-UHFFFAOYSA-O 0.000 description 1
- LDJLHKZKHLFVQE-UHFFFAOYSA-O [OH2+]S1(Cc2ccccc2C1)=O Chemical compound [OH2+]S1(Cc2ccccc2C1)=O LDJLHKZKHLFVQE-UHFFFAOYSA-O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13161487.7 | 2013-03-27 | ||
| EP13161487 | 2013-03-27 | ||
| PCT/EP2014/056081 WO2014154762A1 (en) | 2013-03-27 | 2014-03-26 | Dihydroquinazolinone analogues as brd4 inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016515561A JP2016515561A (ja) | 2016-05-30 |
| JP2016515561A5 JP2016515561A5 (OSRAM) | 2017-05-18 |
| JP6453845B2 true JP6453845B2 (ja) | 2019-01-16 |
Family
ID=47997212
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016504661A Active JP6453845B2 (ja) | 2013-03-27 | 2014-03-26 | Brd4阻害薬としてのジヒドロキナゾリノン類似体 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US9199988B2 (OSRAM) |
| EP (1) | EP2978758B1 (OSRAM) |
| JP (1) | JP6453845B2 (OSRAM) |
| WO (1) | WO2014154762A1 (OSRAM) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9266891B2 (en) | 2012-11-16 | 2016-02-23 | Boehringer Ingelheim International Gmbh | Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| US9073878B2 (en) | 2012-11-21 | 2015-07-07 | Zenith Epigenetics Corp. | Cyclic amines as bromodomain inhibitors |
| US9765039B2 (en) | 2012-11-21 | 2017-09-19 | Zenith Epigenetics Ltd. | Biaryl derivatives as bromodomain inhibitors |
| AU2013365926B9 (en) | 2012-12-21 | 2019-01-17 | Zenith Epigenetics Ltd. | Novel heterocyclic compounds as bromodomain inhibitors |
| SG11201506924YA (en) | 2013-03-15 | 2015-09-29 | Incyte Corp | Tricyclic heterocycles as bet protein inhibitors |
| SI3010503T1 (sl) | 2013-06-21 | 2020-07-31 | Zenith Epigenetics Ltd. | Novi biciklični inhibitorji bromodomene |
| CN105492439B (zh) | 2013-06-21 | 2019-11-22 | 齐尼思表观遗传学有限公司 | 作为溴结构域抑制剂的取代的双环化合物 |
| AR096837A1 (es) | 2013-07-08 | 2016-02-03 | Incyte Corp | Heterociclos tricíclicos como inhibidores de proteínas bet |
| WO2015015318A2 (en) | 2013-07-31 | 2015-02-05 | Zenith Epigenetics Corp. | Novel quinazolinones as bromodomain inhibitors |
| WO2015081203A1 (en) | 2013-11-26 | 2015-06-04 | Incyte Corporation | Bicyclic heterocycles as bet protein inhibitors |
| WO2015081189A1 (en) | 2013-11-26 | 2015-06-04 | Incyte Corporation | Bicyclic heterocycles as bet protein inhibitors |
| US9416128B2 (en) * | 2013-12-19 | 2016-08-16 | Gilead Sciences, Inc. | Fused heterocyclic compounds as ion channel modulators |
| WO2015095492A1 (en) | 2013-12-19 | 2015-06-25 | Incyte Corporation | Tricyclic heterocycles as bet protein inhibitors |
| JP6480944B2 (ja) * | 2014-01-09 | 2019-03-13 | オリオン コーポレーション | ブロモドメイン阻害剤としての二環式複素環誘導体 |
| UA119870C2 (uk) | 2014-04-23 | 2019-08-27 | Інсайт Корпорейшн | 1H-ПІРОЛО[2,3-c]ПІРИДИН-7(6H)-ОНИ ТА ПІРАЗОЛО[3,4-c]ПІРИДИН-7(6H)-ОНИ ЯК ІНГІБІТОРИ БІЛКІВ BET |
| US9527864B2 (en) | 2014-09-15 | 2016-12-27 | Incyte Corporation | Tricyclic heterocycles as BET protein inhibitors |
| EP3227281A4 (en) | 2014-12-01 | 2018-05-30 | Zenith Epigenetics Ltd. | Substituted pyridinones as bromodomain inhibitors |
| HK1246273B (en) | 2014-12-01 | 2019-12-06 | 恒翼生物医药(上海)股份有限公司 | Substituted pyridines as bromodomain inhibitors |
| US10292968B2 (en) | 2014-12-11 | 2019-05-21 | Zenith Epigenetics Ltd. | Substituted heterocycles as bromodomain inhibitors |
| CA2966450A1 (en) | 2014-12-17 | 2016-06-23 | Olesya KHARENKO | Inhibitors of bromodomains |
| WO2016203335A1 (en) | 2015-06-18 | 2016-12-22 | Pfizer Inc. | Novel pyrido[2,3-b]pyrazinones as bet-family bromodomain inhibitors |
| CN105130880B (zh) * | 2015-09-18 | 2017-07-11 | 上海皓伯化工科技有限公司 | 一种制备1‑(3‑甲氧丙基)哌啶‑4‑胺的方法 |
| TW201722966A (zh) | 2015-10-29 | 2017-07-01 | 英塞特公司 | Bet蛋白質抑制劑之非晶固體形式 |
| CN105541825A (zh) * | 2015-12-28 | 2016-05-04 | 中国药科大学 | 三氮唑衍生物制备方法及其作为药物的用途 |
| IL263824B2 (en) | 2016-06-20 | 2023-10-01 | Incyte Corp | Crystals in solid form in the presence of an inhibitor |
| CN107056771A (zh) * | 2017-01-23 | 2017-08-18 | 中国药科大学 | Bromodomain蛋白二价抑制剂及其制备方法和应用 |
| JP7642552B2 (ja) | 2019-09-30 | 2025-03-10 | 協和キリン株式会社 | Bet分解剤 |
| WO2021175432A1 (en) | 2020-03-04 | 2021-09-10 | Boehringer Ingelheim International Gmbh | Method for administration of an anti cancer agent |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
| WO2023274418A1 (zh) * | 2021-07-02 | 2023-01-05 | 南京明德新药研发有限公司 | 蛋白降解靶向嵌合体类化合物 |
| CN114437041B (zh) * | 2022-02-25 | 2023-11-10 | 湖北科技学院 | 一类具有抗肿瘤活性的4-四唑基取代-3,4-二氢喹唑啉衍生物及其制备方法和应用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0919423D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| GB0919432D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Use |
-
2014
- 2014-03-26 JP JP2016504661A patent/JP6453845B2/ja active Active
- 2014-03-26 EP EP14714968.6A patent/EP2978758B1/en active Active
- 2014-03-26 US US14/225,486 patent/US9199988B2/en active Active
- 2014-03-26 WO PCT/EP2014/056081 patent/WO2014154762A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP2978758B1 (en) | 2017-02-08 |
| JP2016515561A (ja) | 2016-05-30 |
| WO2014154762A1 (en) | 2014-10-02 |
| EP2978758A1 (en) | 2016-02-03 |
| US9199988B2 (en) | 2015-12-01 |
| US20140296230A1 (en) | 2014-10-02 |
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