JP2007507551A5 - - Google Patents
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- JP2007507551A5 JP2007507551A5 JP2006534290A JP2006534290A JP2007507551A5 JP 2007507551 A5 JP2007507551 A5 JP 2007507551A5 JP 2006534290 A JP2006534290 A JP 2006534290A JP 2006534290 A JP2006534290 A JP 2006534290A JP 2007507551 A5 JP2007507551 A5 JP 2007507551A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- group
- alkoxy
- cycloalkyl
- 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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- 125000000217 alkyl group Chemical group 0.000 claims 98
- 125000003545 alkoxy group Chemical group 0.000 claims 55
- 150000001875 compounds Chemical class 0.000 claims 53
- 229910052736 halogen Inorganic materials 0.000 claims 42
- 150000002367 halogens Chemical class 0.000 claims 42
- 229910052799 carbon Inorganic materials 0.000 claims 32
- 229910052739 hydrogen Inorganic materials 0.000 claims 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims 22
- 239000000203 mixture Substances 0.000 claims 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims 20
- 125000001424 substituent group Chemical group 0.000 claims 20
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 19
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 18
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 15
- -1 cyano, hydroxy Chemical group 0.000 claims 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 12
- 125000005647 linker group Chemical group 0.000 claims 12
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 11
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 8
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 8
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims 8
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 7
- 125000002252 acyl group Chemical group 0.000 claims 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 7
- 239000003146 anticoagulant agent Substances 0.000 claims 6
- 125000003118 aryl group Chemical group 0.000 claims 6
- 125000004122 cyclic group Chemical group 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims 6
- 125000005842 heteroatom Chemical group 0.000 claims 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 6
- 125000001544 thienyl group Chemical group 0.000 claims 6
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 5
- 125000000304 alkynyl group Chemical group 0.000 claims 5
- 125000001188 haloalkyl group Chemical group 0.000 claims 5
- 229940124597 therapeutic agent Drugs 0.000 claims 5
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims 4
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims 4
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 4
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 4
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims 4
- 229930192474 thiophene Natural products 0.000 claims 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims 3
- 230000000702 anti-platelet effect Effects 0.000 claims 3
- 229940127219 anticoagulant drug Drugs 0.000 claims 3
- 125000002393 azetidinyl group Chemical group 0.000 claims 3
- 125000002619 bicyclic group Chemical group 0.000 claims 3
- 230000000302 ischemic effect Effects 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- 125000003386 piperidinyl group Chemical group 0.000 claims 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 229910052717 sulfur Inorganic materials 0.000 claims 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims 2
- 208000007536 Thrombosis Diseases 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- 206010002388 Angina unstable Diseases 0.000 claims 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims 1
- 206010022562 Intermittent claudication Diseases 0.000 claims 1
- 206010038563 Reocclusion Diseases 0.000 claims 1
- 206010050496 Reversible ischaemic neurological deficit Diseases 0.000 claims 1
- 208000007718 Stable Angina Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 claims 1
- 229940122388 Thrombin inhibitor Drugs 0.000 claims 1
- 229940123987 Thromboxane A2 receptor antagonist Drugs 0.000 claims 1
- 208000032109 Transient ischaemic attack Diseases 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- 229960001138 acetylsalicylic acid Drugs 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 239000003529 anticholesteremic agent Substances 0.000 claims 1
- 229940127226 anticholesterol agent Drugs 0.000 claims 1
- 239000003420 antiserotonin agent Substances 0.000 claims 1
- 230000036772 blood pressure Effects 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000007887 coronary angioplasty Methods 0.000 claims 1
- 229940072645 coumadin Drugs 0.000 claims 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims 1
- 230000000994 depressogenic effect Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003527 fibrinolytic agent Substances 0.000 claims 1
- 229960002897 heparin Drugs 0.000 claims 1
- 229920000669 heparin Polymers 0.000 claims 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
- 208000021156 intermittent vascular claudication Diseases 0.000 claims 1
- 229940118179 lovenox Drugs 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims 1
- 239000002570 phosphodiesterase III inhibitor Substances 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 239000003868 thrombin inhibitor Substances 0.000 claims 1
- 230000001732 thrombotic effect Effects 0.000 claims 1
- 239000003769 thromboxane A2 receptor blocking agent Substances 0.000 claims 1
- 201000010875 transient cerebral ischemia Diseases 0.000 claims 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 claims 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50856403P | 2003-10-03 | 2003-10-03 | |
| PCT/US2004/032921 WO2005032488A2 (en) | 2003-10-03 | 2004-09-29 | 2,4-dioxo-3-quinazolinylaryl sulfonylureas |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007507551A JP2007507551A (ja) | 2007-03-29 |
| JP2007507551A5 true JP2007507551A5 (https=) | 2007-11-08 |
Family
ID=34421757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006534290A Pending JP2007507551A (ja) | 2003-10-03 | 2004-09-29 | ２，４−ジオキソ−３−キナゾリニルアリールスルホニル尿素 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US7109332B2 (https=) |
| EP (1) | EP1668002B1 (https=) |
| JP (1) | JP2007507551A (https=) |
| KR (1) | KR20060113700A (https=) |
| CN (1) | CN1863798B (https=) |
| AT (1) | ATE448222T1 (https=) |
| AU (1) | AU2004278030C1 (https=) |
| CA (1) | CA2540214A1 (https=) |
| DE (1) | DE602004024093D1 (https=) |
| ES (1) | ES2334795T3 (https=) |
| IL (1) | IL174446A (https=) |
| MX (1) | MXPA06003618A (https=) |
| PL (1) | PL1668002T3 (https=) |
| PT (1) | PT1668002E (https=) |
| WO (1) | WO2005032488A2 (https=) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7345049B2 (en) * | 2003-12-22 | 2008-03-18 | Ajinomoto Co., Inc. | Phenylalanine derivatives |
| EP1812429A4 (en) * | 2004-09-29 | 2010-07-21 | Portola Pharm Inc | SUBSTITUTED 2H-1,3-BENZOXAZIN-4 (3H) -ONE |
| PT1951254E (pt) * | 2005-11-03 | 2012-04-12 | Portola Pharm Inc | [4-(6-halo-7-substituído-2,4-dioxo-1,4-di-hidro-2hquinazolin- 3-il)-fenil]-5-cloro-tiofen-2-il-sulfonilureias e formas e métodos relacionados com as mesmas |
| US7834023B2 (en) * | 2006-09-20 | 2010-11-16 | Portola Pharmaceuticals, Inc. | Substituted dihydroquinazolines as platelet ADP receptor inhibitors |
| WO2008124532A1 (en) * | 2007-04-05 | 2008-10-16 | Cv Therapeutics, Inc. | Quinazolinone derivatives as aldh-2 inhibitors |
| US20100113391A1 (en) | 2007-04-19 | 2010-05-06 | Astellas Pharma Inc. | Bicyclic heterocyclic compound |
| WO2008137809A2 (en) * | 2007-05-02 | 2008-11-13 | Portola Pharmaceuticals, Inc. | [4-(6-fluoro-7-methylamino-2,4-dioxo-1,4-dihydro-2h-quinazolin-3-yl)-phenyl] -5-chloro-thiophen-2-yl-sulfonylurea salts, in different crystalline forms, pharmaceutical compositions thereof |
| CN101654441B (zh) * | 2008-08-19 | 2012-10-03 | 信谊药厂 | 抗凝化合物、组合物及其用途 |
| WO2010083442A1 (en) * | 2009-01-19 | 2010-07-22 | Abbott Laboratories | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| CA2747835A1 (en) | 2009-01-19 | 2010-07-22 | Abbott Laboratories | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| JP6014155B2 (ja) | 2011-10-31 | 2016-10-25 | ゼノン・ファーマシューティカルズ・インコーポレイテッドＸｅｎｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃ． | ビアリールエーテルスルホンアミドおよび治療剤としてのそれらの使用 |
| US9630929B2 (en) | 2011-10-31 | 2017-04-25 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
| SG11201408284VA (en) * | 2012-05-22 | 2015-02-27 | Xenon Pharmaceuticals Inc | N-substituted benzamides and their use in the treatment of pain |
| US10071957B2 (en) | 2012-07-06 | 2018-09-11 | Genentech, Inc. | N-substituted benzamides and methods of use thereof |
| US9550775B2 (en) | 2013-03-14 | 2017-01-24 | Genentech, Inc. | Substituted triazolopyridines and methods of use thereof |
| MX2015010775A (es) | 2013-03-15 | 2016-04-25 | Genentech Inc | Benzoxazoles sustituidos y metodos para usarlos. |
| CR20160296A (es) | 2013-11-27 | 2016-09-20 | Genentech Inc | Benzamidas sustituidas y métodos para usarlas |
| CN106715418A (zh) | 2014-07-07 | 2017-05-24 | 基因泰克公司 | 治疗化合物及其使用方法 |
| KR102727059B1 (ko) | 2015-02-16 | 2024-11-05 | 더 유니버서티 어브 퀸슬랜드 | 설포닐우레아와 관련 화합물 및 그 용도 |
| JP2018520107A (ja) | 2015-05-22 | 2018-07-26 | ジェネンテック， インコーポレイテッド | 置換ベンズアミド及びその使用方法 |
| EP3341353A1 (en) | 2015-08-27 | 2018-07-04 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| CN108290881B (zh) | 2015-09-28 | 2021-12-07 | 健泰科生物技术公司 | 治疗性化合物和其使用方法 |
| US10899732B2 (en) | 2015-11-25 | 2021-01-26 | Genentech, Inc. | Substituted benzamides useful as sodium channel blockers |
| EP3854782A1 (en) | 2016-03-30 | 2021-07-28 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
| AU2017347549A1 (en) | 2016-10-17 | 2019-05-02 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| JP2020511511A (ja) | 2017-03-24 | 2020-04-16 | ジェネンテック， インコーポレイテッド | ナトリウムチャネル阻害剤としての４−ピペリジン−ｎ−（ピリミジン−４−イル）クロマン−７−スルホンアミド誘導体 |
| US11465992B2 (en) | 2017-07-07 | 2022-10-11 | Inflazome Limited | Sulfonamide carboxamide compounds |
| US11542255B2 (en) | 2017-08-15 | 2023-01-03 | Inflazome Limited | Sulfonylureas and sulfonylthioureas as NLRP3 inhibitors |
| WO2019034693A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3 |
| MX2020001776A (es) | 2017-08-15 | 2020-03-24 | Inflazome Ltd | Sulfonilureas y sulfoniltioureas como inhibidores de nlrp3. |
| US12221434B2 (en) | 2017-11-09 | 2025-02-11 | Inflazome Limited | Sulfonamide carboxamide compounds |
| KR20200087759A (ko) | 2017-11-09 | 2020-07-21 | 인플라좀 리미티드 | 신규한 설폰아마이드 카복스아마이드 화합물 |
| AR114263A1 (es) | 2018-02-26 | 2020-08-12 | Genentech Inc | Compuestos terapéuticos y métodos para utilizarlos |
| EP3759077A1 (en) | 2018-03-02 | 2021-01-06 | Inflazome Limited | Novel compounds |
| WO2019191702A1 (en) | 2018-03-30 | 2019-10-03 | F. Hoffmann-La Roche Ag | Substituted hydro-pyrido-azines as sodium channel inhibitors |
| TW202003490A (zh) | 2018-05-22 | 2020-01-16 | 瑞士商赫孚孟拉羅股份公司 | 治療性化合物及其使用方法 |
| AU2019395201A1 (en) | 2018-12-06 | 2021-05-20 | Daiichi Sankyo Company, Limited | Cycloalkane-1,3-diamine derivative |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9702774D0 (sv) | 1997-07-22 | 1997-07-22 | Astra Pharma Prod | Novel compounds |
| CA2318199A1 (en) | 1998-01-15 | 1999-07-22 | Cor Therapeutics, Inc. | Platelet adp receptor inhibitors |
| US6906063B2 (en) * | 2000-02-04 | 2005-06-14 | Portola Pharmaceuticals, Inc. | Platelet ADP receptor inhibitors |
| WO2001057037A1 (en) * | 2000-02-04 | 2001-08-09 | Cor Therapeutics, Inc. | Platelet adp receptor inhibitors |
-
2004
- 2004-09-29 ES ES04789522T patent/ES2334795T3/es not_active Expired - Lifetime
- 2004-09-29 AT AT04789522T patent/ATE448222T1/de active
- 2004-09-29 CA CA002540214A patent/CA2540214A1/en not_active Abandoned
- 2004-09-29 EP EP04789522A patent/EP1668002B1/en not_active Expired - Lifetime
- 2004-09-29 US US10/956,004 patent/US7109332B2/en not_active Expired - Fee Related
- 2004-09-29 WO PCT/US2004/032921 patent/WO2005032488A2/en not_active Ceased
- 2004-09-29 MX MXPA06003618A patent/MXPA06003618A/es active IP Right Grant
- 2004-09-29 PL PL04789522T patent/PL1668002T3/pl unknown
- 2004-09-29 CN CN2004800287913A patent/CN1863798B/zh not_active Expired - Fee Related
- 2004-09-29 DE DE602004024093T patent/DE602004024093D1/de not_active Expired - Lifetime
- 2004-09-29 KR KR1020067008644A patent/KR20060113700A/ko not_active Ceased
- 2004-09-29 AU AU2004278030A patent/AU2004278030C1/en not_active Ceased
- 2004-09-29 PT PT04789522T patent/PT1668002E/pt unknown
- 2004-09-29 JP JP2006534290A patent/JP2007507551A/ja active Pending
-
2006
- 2006-03-21 IL IL174446A patent/IL174446A/en not_active IP Right Cessation
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