JP2006511486A5 - - Google Patents
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- Publication number
- JP2006511486A5 JP2006511486A5 JP2004544591A JP2004544591A JP2006511486A5 JP 2006511486 A5 JP2006511486 A5 JP 2006511486A5 JP 2004544591 A JP2004544591 A JP 2004544591A JP 2004544591 A JP2004544591 A JP 2004544591A JP 2006511486 A5 JP2006511486 A5 JP 2006511486A5
- Authority
- JP
- Japan
- Prior art keywords
- use according
- sarm
- nhcor
- conhr
- snr
- 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.)
- Abandoned
Links
- 239000000849 selective androgen receptor modulator Substances 0.000 claims 88
- 229940083324 Selective androgen receptor modulator Drugs 0.000 claims 86
- 125000000217 alkyl group Chemical group 0.000 claims 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 48
- 150000001875 compounds Chemical class 0.000 claims 40
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 28
- 239000000126 substance Substances 0.000 claims 28
- 101100149678 Caenorhabditis elegans snr-3 gene Proteins 0.000 claims 24
- 125000004122 cyclic group Chemical group 0.000 claims 24
- 239000003814 drug Substances 0.000 claims 24
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 20
- 125000003342 alkenyl group Chemical group 0.000 claims 20
- 125000004982 dihaloalkyl group Chemical group 0.000 claims 20
- 125000001188 haloalkyl group Chemical group 0.000 claims 20
- 125000004385 trihaloalkyl group Chemical group 0.000 claims 20
- 230000000694 effects Effects 0.000 claims 16
- 229910052760 oxygen Inorganic materials 0.000 claims 16
- 210000002307 prostate Anatomy 0.000 claims 14
- 230000003042 antagnostic effect Effects 0.000 claims 12
- 230000008878 coupling Effects 0.000 claims 12
- 238000010168 coupling process Methods 0.000 claims 12
- 238000005859 coupling reaction Methods 0.000 claims 12
- 229940079593 drug Drugs 0.000 claims 12
- 210000003205 muscle Anatomy 0.000 claims 12
- 229910052717 sulfur Inorganic materials 0.000 claims 12
- 102000007399 Nuclear hormone receptor Human genes 0.000 claims 8
- 108020005497 Nuclear hormone receptor Proteins 0.000 claims 8
- 239000003098 androgen Substances 0.000 claims 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims 8
- 210000000988 bone and bone Anatomy 0.000 claims 8
- 210000003169 central nervous system Anatomy 0.000 claims 8
- 239000013078 crystal Substances 0.000 claims 8
- 229910052739 hydrogen Inorganic materials 0.000 claims 8
- 239000001257 hydrogen Substances 0.000 claims 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 8
- 239000007788 liquid Substances 0.000 claims 8
- 239000002207 metabolite Substances 0.000 claims 8
- 239000008188 pellet Substances 0.000 claims 8
- -1 polymorphs Substances 0.000 claims 8
- 229940002612 prodrug Drugs 0.000 claims 8
- 239000000651 prodrug Substances 0.000 claims 8
- 150000003839 salts Chemical class 0.000 claims 8
- 239000007787 solid Substances 0.000 claims 8
- 201000004384 Alopecia Diseases 0.000 claims 6
- 208000010228 Erectile Dysfunction Diseases 0.000 claims 6
- 206010058359 Hypogonadism Diseases 0.000 claims 6
- 208000029725 Metabolic bone disease Diseases 0.000 claims 6
- 206010027940 Mood altered Diseases 0.000 claims 6
- 208000008589 Obesity Diseases 0.000 claims 6
- 206010049088 Osteopenia Diseases 0.000 claims 6
- 208000001132 Osteoporosis Diseases 0.000 claims 6
- 206010060862 Prostate cancer Diseases 0.000 claims 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 6
- 201000001880 Sexual dysfunction Diseases 0.000 claims 6
- 231100000360 alopecia Toxicity 0.000 claims 6
- 208000007502 anemia Diseases 0.000 claims 6
- 230000001149 cognitive effect Effects 0.000 claims 6
- 230000003247 decreasing effect Effects 0.000 claims 6
- 201000001881 impotence Diseases 0.000 claims 6
- 230000007510 mood change Effects 0.000 claims 6
- 235000020824 obesity Nutrition 0.000 claims 6
- 231100000872 sexual dysfunction Toxicity 0.000 claims 6
- 229940124011 Androgen receptor agonist Drugs 0.000 claims 4
- 229940123407 Androgen receptor antagonist Drugs 0.000 claims 4
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims 4
- 150000001204 N-oxides Chemical class 0.000 claims 4
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims 4
- 230000001270 agonistic effect Effects 0.000 claims 4
- 239000003936 androgen receptor antagonist Substances 0.000 claims 4
- 239000002775 capsule Substances 0.000 claims 4
- 239000006071 cream Substances 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 4
- 239000000839 emulsion Substances 0.000 claims 4
- 239000012530 fluid Substances 0.000 claims 4
- 238000009472 formulation Methods 0.000 claims 4
- 239000000499 gel Substances 0.000 claims 4
- 150000004677 hydrates Chemical class 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- 239000000243 solution Substances 0.000 claims 4
- 239000000829 suppository Substances 0.000 claims 4
- 239000000725 suspension Substances 0.000 claims 4
- 208000024891 symptom Diseases 0.000 claims 4
- 239000003826 tablet Substances 0.000 claims 4
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 claims 3
- 230000002401 inhibitory effect Effects 0.000 claims 3
- 206010020880 Hypertrophy Diseases 0.000 claims 2
- 230000005764 inhibitory process Effects 0.000 claims 2
- 230000003405 preventing effect Effects 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 230000001603 reducing effect Effects 0.000 claims 2
- 230000009467 reduction Effects 0.000 claims 2
- 208000001076 sarcopenia Diseases 0.000 claims 2
- 230000001629 suppression Effects 0.000 claims 2
- 101000685982 Homo sapiens NAD(+) hydrolase SARM1 Proteins 0.000 claims 1
- 102100023356 NAD(+) hydrolase SARM1 Human genes 0.000 claims 1
- 230000007423 decrease Effects 0.000 claims 1
- 0 C*C1C=CC(NC([C@](C)(C*c2ccc(*C)cc2)O)=O)=CC1* Chemical compound C*C1C=CC(NC([C@](C)(C*c2ccc(*C)cc2)O)=O)=CC1* 0.000 description 4
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP20020292606 EP1413306A1 (en) | 2002-10-21 | 2002-10-21 | Tetrahydroquinoline derivatives as CRTH2 antagonists |
| US43489602P | 2002-12-19 | 2002-12-19 | |
| PCT/IB2003/004505 WO2004035543A1 (en) | 2002-10-21 | 2003-10-10 | Tetrahydroquinoline derivatives as crth2 antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006511486A JP2006511486A (ja) | 2006-04-06 |
| JP2006511486A5 true JP2006511486A5 (enExample) | 2006-08-17 |
Family
ID=32109153
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004544591A Abandoned JP2006511486A (ja) | 2002-10-21 | 2003-10-10 | Ｃｒｔｈ２拮抗剤としてのテトラヒドロキノリン誘導体 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7220760B2 (enExample) |
| EP (1) | EP1556356B1 (enExample) |
| JP (1) | JP2006511486A (enExample) |
| AT (1) | ATE327977T1 (enExample) |
| AU (1) | AU2003269327A1 (enExample) |
| BR (1) | BR0315547A (enExample) |
| CA (1) | CA2500083A1 (enExample) |
| DE (1) | DE60305724T2 (enExample) |
| ES (1) | ES2263015T3 (enExample) |
| MX (1) | MXPA05003660A (enExample) |
| WO (1) | WO2004035543A1 (enExample) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7504508B2 (en) | 2002-10-04 | 2009-03-17 | Millennium Pharmaceuticals, Inc. | PGD2 receptor antagonists for the treatment of inflammatory diseases |
| PL376156A1 (en) | 2002-10-04 | 2005-12-27 | Millennium Pharmaceuticals, Inc. | Pgd2 receptor antagonists for the treatment of inflammatory diseases |
| AU2003269327A1 (en) * | 2002-10-21 | 2004-05-04 | Warner-Lambert Company Llc | Tetrahydroquinoline derivatives as crth2 antagonists |
| EP1435356A1 (en) * | 2003-01-06 | 2004-07-07 | Warner-Lambert Company LLC | Quinoline derivatives as CRTH2 antagonists |
| CA2531327A1 (en) | 2003-07-03 | 2005-01-13 | Myriad Genetics, Inc. | Compounds and therapeutical use thereof |
| US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
| US20050038070A1 (en) * | 2003-07-09 | 2005-02-17 | Amgen Inc. | Asthma and allergic inflammation modulators |
| JP4051398B2 (ja) | 2004-03-11 | 2008-02-20 | アクテリオン ファマシューティカルズ リミテッド | テトラヒドロピリドインドール誘導体 |
| TW200538127A (en) * | 2004-04-07 | 2005-12-01 | Millennium Pharm Inc | PGD2 receptor antagonists for the treatment of inflammatory diseases |
| WO2005102338A1 (en) * | 2004-04-20 | 2005-11-03 | Pfizer Limited | Method of treating neuropathic pain using a crth2 receptor antagonist |
| US8969379B2 (en) | 2004-09-17 | 2015-03-03 | Eisai R&D Management Co., Ltd. | Pharmaceutical compositions of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7=methoxy-6-quinolinecarboxide |
| US20060063803A1 (en) * | 2004-09-23 | 2006-03-23 | Pfizer Inc | 4-Amino substituted-2-substituted-1,2,3,4-tetrahydroquinoline compounds |
| US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| CA2592900A1 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
| BRPI0607241A2 (pt) * | 2005-01-26 | 2009-08-25 | Hoffmann La Roche | derivados de fenil metanona e o uso dos mesmos como inibidores do transportador de glicina 1 |
| BRPI0608553A2 (pt) * | 2005-02-24 | 2010-01-12 | Millennium Pharm Inc | antagonistas de receptor de pgd2 para o tratamento de doenças inflamatórias |
| ATE524182T1 (de) | 2005-04-21 | 2011-09-15 | Merck Serono Sa | 2,3-substituierte pyrazinsulfonamide als crth2- hemmer |
| WO2006125784A1 (en) | 2005-05-24 | 2006-11-30 | Laboratoires Serono S.A. | Tricyclic spiro derivatives as crth2 modulators |
| HUE030850T2 (en) | 2006-06-16 | 2017-06-28 | Univ Pennsylvania | Prostaglandin D2 receptor antagonists for the treatment of hair loss |
| TW200831085A (en) * | 2006-12-13 | 2008-08-01 | Merck & Co Inc | Non-nucleoside reverse transcriptase inhibitors |
| WO2009041072A1 (ja) | 2007-09-27 | 2009-04-02 | Kowa Company, Ltd. | テトラヒドロキノリン化合物を有効成分とする貧血の予防及び／又は治療剤 |
| JP5327762B2 (ja) | 2007-12-14 | 2013-10-30 | プルマジェン セラピューティクス（アズマ）リミテッド | インドールおよびその治療的使用 |
| US8067445B2 (en) | 2008-02-01 | 2011-11-29 | Panmira Pharmaceuticals, Llc | N,N-disubstituted aminoalkylbiphenyl antagonists of prostaglandin D2 receptors |
| US8497381B2 (en) | 2008-02-25 | 2013-07-30 | Panmira Pharmaceuticals, Llc | Antagonists of prostaglandin D2 receptors |
| JP5437232B2 (ja) * | 2008-03-11 | 2014-03-12 | あすか製薬株式会社 | 固体分散体とその医薬組成物、並びにそれらの製造方法 |
| GB2463788B (en) | 2008-09-29 | 2010-12-15 | Amira Pharmaceuticals Inc | Heteroaryl antagonists of prostaglandin D2 receptors |
| WO2010039977A2 (en) | 2008-10-01 | 2010-04-08 | Amira Pharmaceuticals, Inc. | Heteroaryl antagonists of prostaglandin d2 receptors |
| US8524748B2 (en) | 2008-10-08 | 2013-09-03 | Panmira Pharmaceuticals, Llc | Heteroalkyl biphenyl antagonists of prostaglandin D2 receptors |
| GB2465062B (en) | 2008-11-06 | 2011-04-13 | Amira Pharmaceuticals Inc | Cycloalkane(B)azaindole antagonists of prostaglandin D2 receptors |
| KR20110071122A (ko) * | 2008-11-17 | 2011-06-28 | 에프. 호프만-라 로슈 아게 | 나프틸아세트산 |
| WO2010092043A1 (en) | 2009-02-12 | 2010-08-19 | Merck Serono S.A. | Phenoxy acetic acid derivatives |
| WO2010113498A1 (ja) | 2009-03-31 | 2010-10-07 | 興和株式会社 | テトラヒドロキノリン化合物を有効成分とする貧血の予防及び／又は治療剤 |
| WO2011014587A2 (en) | 2009-07-31 | 2011-02-03 | Amira Pharmaceuticals, Inc. | Ophthalmic pharmaceutical compositions of dp2 receptor antagonists |
| KR20120047273A (ko) | 2009-08-05 | 2012-05-11 | 판미라 파마슈티칼스, 엘엘씨 | Ｄｐ2 길항제 및 이의 용도 |
| CA2771403C (en) * | 2009-08-19 | 2015-02-24 | Eisai R&D Management Co. Ltd. | Quinoline derivative-containing pharmaceutical composition |
| CA2805452C (en) | 2010-07-05 | 2018-07-31 | Actelion Pharmaceuticals Ltd | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin d2 receptor modulators |
| BR112013015397A2 (pt) * | 2010-12-23 | 2016-09-20 | Merck Sharp & Dohme | composto, composição farmacêutica, e, uso de um composto |
| JP6038128B2 (ja) | 2011-06-03 | 2016-12-07 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | レンバチニブ化合物に対する甲状腺癌対象及び腎臓癌対象の反応性を予測及び評価するためのバイオマーカー |
| PH12013502619A1 (en) | 2011-06-17 | 2014-02-17 | Merck Sharp & Dohme | Cycloalkyl-fused tetrahydroquinolines as crth2 receptor modulators |
| CN104114169A (zh) | 2011-12-16 | 2014-10-22 | 阿托佩斯治疗有限公司 | 用于治疗嗜酸细胞性食管炎的crth2拮抗剂和质子泵抑制剂的组合物 |
| TW201331179A (zh) | 2011-12-21 | 2013-08-01 | Actelion Pharmaceuticals Ltd | 雜環衍生物及其作為前列腺素ｄ２受體調節劑之用途 |
| JP6193968B2 (ja) | 2012-03-21 | 2017-09-06 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 発毛を調節するための組成物および方法 |
| EP2885307A1 (en) | 2012-07-05 | 2015-06-24 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin d2 receptor modulators |
| JPWO2014098176A1 (ja) | 2012-12-21 | 2017-01-12 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | キノリン誘導体のアモルファス及びその製造方法 |
| CA2912219C (en) | 2013-05-14 | 2021-11-16 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| EP3187491A4 (en) | 2014-08-28 | 2018-08-01 | Eisai R&D Management Co., Ltd. | High-purity quinoline derivative and method for manufacturing same |
| JP6770522B2 (ja) | 2015-02-13 | 2020-10-14 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 全身性エリテマトーデスを予防し、及び／又は、治療するためのｐｔｇｄｒ−１及び／又はｐｔｇｄｒ−２アンタゴニスト |
| US20180028662A1 (en) | 2015-02-25 | 2018-02-01 | Eisai R&D Management Co., Ltd. | Method for Suppressing Bitterness of Quinoline Derivative |
| KR20240064733A (ko) | 2015-03-04 | 2024-05-13 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| CA2988707C (en) | 2015-06-16 | 2023-10-10 | Eisai R&D Management Co., Ltd. | Combination of cbp/catenin inhibitor and immune checkpoint inhibitor for treating cancer |
| ES2947824T3 (es) | 2015-07-30 | 2023-08-21 | Univ Pennsylvania | Alelos polimórficos de un solo nucleótido del gen DP-2 humano para la detección de la susceptibilidad a la inhibición del crecimiento del cabello por antagonistas de PGD2 |
| CN108135894B (zh) | 2015-08-20 | 2021-02-19 | 卫材R&D管理有限公司 | 肿瘤治疗剂 |
| CN110072528B (zh) | 2017-02-08 | 2022-04-26 | 卫材R&D管理有限公司 | 治疗肿瘤的药物组合物 |
| WO2018212202A1 (en) | 2017-05-16 | 2018-11-22 | Eisai R&D Management Co., Ltd. | Treatment of hepatocellular carcinoma |
| CN115947683B (zh) * | 2022-12-29 | 2025-08-05 | 湖南工程学院 | 一种四氢喹啉及其衍生物的合成方法 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4521607A (en) | 1981-02-27 | 1985-06-04 | Takeda Chemical Industries, Ltd. | Chromanyl glycines |
| KR0167349B1 (ko) | 1989-10-20 | 1999-02-18 | 오스카 아끼히꼬 | 벤조헤테로 고리 화합물 |
| US5753677A (en) * | 1989-10-20 | 1998-05-19 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclic compounds |
| US6168784B1 (en) * | 1997-09-03 | 2001-01-02 | Gryphon Sciences | N-terminal modifications of RANTES and methods of use |
| GT199900147A (es) | 1998-09-17 | 1999-09-06 | 1, 2, 3, 4- tetrahidroquinolinas 2-sustituidas 4-amino sustituidas. | |
| US6147090A (en) | 1998-09-17 | 2000-11-14 | Pfizer Inc. | 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| US6197786B1 (en) | 1998-09-17 | 2001-03-06 | Pfizer Inc | 4-Carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines |
| US6147089A (en) | 1998-09-17 | 2000-11-14 | Pfizer Inc. | Annulated 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| US6140342A (en) | 1998-09-17 | 2000-10-31 | Pfizer Inc. | Oxy substituted 4-carboxyamino-2-methyl-1,2,3,4-tetrahydroquinolines |
| US6878522B2 (en) * | 2000-07-07 | 2005-04-12 | Baiyong Li | Methods for the identification of compounds useful for the treatment of disease states mediated by prostaglandin D2 |
| JP2002053557A (ja) | 2000-08-14 | 2002-02-19 | Japan Tobacco Inc | アポリポ蛋白ａ−ｉ産生促進薬 |
| SE0101161D0 (sv) | 2001-03-30 | 2001-03-30 | Astrazeneca Ab | New compounds |
| US20050228016A1 (en) | 2002-06-13 | 2005-10-13 | Enrique Michelotti | Tetrahydroquinolines for modulating the expression of exogenous genes via an ecdysone receptor complex |
| PL376156A1 (en) | 2002-10-04 | 2005-12-27 | Millennium Pharmaceuticals, Inc. | Pgd2 receptor antagonists for the treatment of inflammatory diseases |
| AU2003269327A1 (en) * | 2002-10-21 | 2004-05-04 | Warner-Lambert Company Llc | Tetrahydroquinoline derivatives as crth2 antagonists |
| JPWO2004052863A1 (ja) | 2002-12-06 | 2006-04-13 | 協和醗酵工業株式会社 | 抗炎症剤 |
| US20040204450A1 (en) * | 2003-03-28 | 2004-10-14 | Pfizer Inc | Quinoline and quinoxaline compounds |
| US20050038070A1 (en) | 2003-07-09 | 2005-02-17 | Amgen Inc. | Asthma and allergic inflammation modulators |
| US20060063803A1 (en) | 2004-09-23 | 2006-03-23 | Pfizer Inc | 4-Amino substituted-2-substituted-1,2,3,4-tetrahydroquinoline compounds |
| US20070149567A1 (en) * | 2004-09-23 | 2007-06-28 | Pfizer Inc | Quinoline compounds |
-
2003
- 2003-10-10 AU AU2003269327A patent/AU2003269327A1/en not_active Abandoned
- 2003-10-10 CA CA002500083A patent/CA2500083A1/en not_active Abandoned
- 2003-10-10 AT AT03751107T patent/ATE327977T1/de not_active IP Right Cessation
- 2003-10-10 JP JP2004544591A patent/JP2006511486A/ja not_active Abandoned
- 2003-10-10 MX MXPA05003660A patent/MXPA05003660A/es unknown
- 2003-10-10 ES ES03751107T patent/ES2263015T3/es not_active Expired - Lifetime
- 2003-10-10 EP EP03751107A patent/EP1556356B1/en not_active Expired - Lifetime
- 2003-10-10 DE DE60305724T patent/DE60305724T2/de not_active Expired - Fee Related
- 2003-10-10 WO PCT/IB2003/004505 patent/WO2004035543A1/en not_active Ceased
- 2003-10-10 BR BR0315547-1A patent/BR0315547A/pt not_active IP Right Cessation
- 2003-10-17 US US10/688,566 patent/US7220760B2/en not_active Expired - Fee Related
-
2007
- 2007-04-16 US US11/735,686 patent/US20070197587A1/en not_active Abandoned
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