BR0317459A - Novos derivados de piperidina como moduladores do receptor ccr5 quimiocina - Google Patents
Novos derivados de piperidina como moduladores do receptor ccr5 quimiocinaInfo
- Publication number
- BR0317459A BR0317459A BR0317459-0A BR0317459A BR0317459A BR 0317459 A BR0317459 A BR 0317459A BR 0317459 A BR0317459 A BR 0317459A BR 0317459 A BR0317459 A BR 0317459A
- Authority
- BR
- Brazil
- Prior art keywords
- piperidine derivatives
- ccr5 receptor
- receptor modulators
- new piperidine
- chemokine ccr5
- Prior art date
Links
- 102000004274 CCR5 Receptors Human genes 0.000 title abstract 2
- 108010017088 CCR5 Receptors Proteins 0.000 title abstract 2
- 102000019034 Chemokines Human genes 0.000 title 1
- 108010012236 Chemokines Proteins 0.000 title 1
- 150000003053 piperidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 2
- 238000000034 method Methods 0.000 abstract 2
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 abstract 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 abstract 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/24—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by sulfur atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/96—Sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Virology (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Transplantation (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- AIDS & HIV (AREA)
- Molecular Biology (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0203821A SE0203821D0 (sv) | 2002-12-20 | 2002-12-20 | Chemical Compounds |
| SE0300499A SE0300499D0 (sv) | 2003-02-24 | 2003-02-24 | Chemical compounds |
| SE0301425A SE0301425D0 (sv) | 2003-05-15 | 2003-05-15 | Chemical compounds |
| PCT/SE2003/002008 WO2004056773A1 (en) | 2002-12-20 | 2003-12-18 | Novel piperidine derivatives as modulators of chemokine receptor ccr5 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR0317459A true BR0317459A (pt) | 2005-11-16 |
Family
ID=32685861
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR0317459-0A BR0317459A (pt) | 2002-12-20 | 2003-12-18 | Novos derivados de piperidina como moduladores do receptor ccr5 quimiocina |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20060189650A1 (enExample) |
| EP (1) | EP1572650A1 (enExample) |
| JP (1) | JP2006514107A (enExample) |
| KR (1) | KR20050084424A (enExample) |
| AR (1) | AR042628A1 (enExample) |
| AU (1) | AU2003288856B2 (enExample) |
| BR (1) | BR0317459A (enExample) |
| CA (1) | CA2508624A1 (enExample) |
| CL (1) | CL2003002678A1 (enExample) |
| CO (1) | CO5570665A2 (enExample) |
| IS (1) | IS7942A (enExample) |
| MX (1) | MXPA05006381A (enExample) |
| NZ (1) | NZ540780A (enExample) |
| PL (1) | PL377768A1 (enExample) |
| TW (1) | TW200505856A (enExample) |
| UY (1) | UY28139A1 (enExample) |
| WO (1) | WO2004056773A1 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0103818D0 (sv) | 2001-11-15 | 2001-11-15 | Astrazeneca Ab | Chemical compounds |
| SE0301369D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Chemical compounds |
| SE0302090D0 (sv) * | 2003-07-16 | 2003-07-16 | Astrazeneca Ab | Chemical compounds |
| JP2007500694A (ja) * | 2003-07-31 | 2007-01-18 | アストラゼネカ・アクチエボラーグ | Ｃｃｒ５受容体モジュレーターとしてのピペリジン誘導体 |
| TW200610761A (en) * | 2004-04-23 | 2006-04-01 | Astrazeneca Ab | Chemical compounds |
| PT1761542E (pt) | 2004-06-09 | 2008-03-26 | Hoffmann La Roche | Derivados de octa-hidro-pirrolo[3,4-c) pirrole e o seu uso com agentes antivirais |
| SE0401657D0 (sv) * | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | Chemical compounds |
| SE0401656D0 (sv) * | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | Chemical compounds |
| US7665658B2 (en) | 2005-06-07 | 2010-02-23 | First Data Corporation | Dynamic aggregation of payment transactions |
| JP2009515826A (ja) | 2005-10-19 | 2009-04-16 | エフ．ホフマン−ラ ロシュ アーゲー | フェニル−アセトアミドｎｎｒｔ阻害剤 |
| PT2057125E (pt) | 2006-08-16 | 2011-05-31 | Hoffmann La Roche | Inibidores n?o nucle?sidos de transcriptase inversa |
| AU2007299992A1 (en) * | 2006-09-28 | 2008-04-03 | Arete Therapeutics, Inc. | Soluble epoxide hydrolase inhibitors |
| KR101475091B1 (ko) | 2006-12-13 | 2014-12-22 | 에프. 호프만-라 로슈 아게 | 비뉴클레오시드 역전사 효소 억제제로서 2-(피페리딘-4-일)-4-페녹시- 또는 페닐아미노-피리미딘 유도체 |
| TW201130810A (en) | 2009-12-23 | 2011-09-16 | Ironwood Pharmaceuticals Inc | CRTH2 modulators |
| US20130259830A1 (en) | 2010-07-12 | 2013-10-03 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
| WO2012009137A1 (en) | 2010-07-12 | 2012-01-19 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
| WO2018068296A1 (en) | 2016-10-14 | 2018-04-19 | Merck Sharp & Dohme Corp. | PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE |
| US11629196B2 (en) | 2020-04-27 | 2023-04-18 | Incelldx, Inc. | Method of treating SARS-CoV-2-associated hypercytokinemia by administering a human monoclonal antibody (PRO-140) that inhibits CCR5/CCL5 binding interactions |
| CN113444065A (zh) * | 2021-06-29 | 2021-09-28 | 浙江得乐康食品股份有限公司 | 一种莽草酸磺化物及其制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX9100513A (es) * | 1990-08-06 | 1992-04-01 | Smith Kline French Lab | Compuestos |
| IL125658A0 (en) * | 1997-08-18 | 1999-04-11 | Hoffmann La Roche | Ccr-3 receptor antagonists |
| EP1013276A1 (en) * | 1998-12-23 | 2000-06-28 | Pfizer Inc. | Aminoazacycloalkanes as CCR5 modulators |
| US6432981B1 (en) * | 1999-06-11 | 2002-08-13 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
| GB0011838D0 (en) * | 2000-05-17 | 2000-07-05 | Astrazeneca Ab | Chemical compounds |
| GB0013060D0 (en) * | 2000-05-31 | 2000-07-19 | Astrazeneca Ab | Chemical compounds |
| GB0108046D0 (en) * | 2001-03-30 | 2001-05-23 | Astrazeneca Ab | Chemical compounds |
| WO2003062224A1 (en) * | 2002-01-17 | 2003-07-31 | Eli Lilly And Company | Aza-cyclic compounds as modulators of acetylcholine receptors |
-
2003
- 2003-12-17 AR ARP030104682A patent/AR042628A1/es not_active Application Discontinuation
- 2003-12-18 KR KR1020057011450A patent/KR20050084424A/ko not_active Withdrawn
- 2003-12-18 WO PCT/SE2003/002008 patent/WO2004056773A1/en not_active Ceased
- 2003-12-18 MX MXPA05006381A patent/MXPA05006381A/es active IP Right Grant
- 2003-12-18 US US10/539,859 patent/US20060189650A1/en not_active Abandoned
- 2003-12-18 CA CA002508624A patent/CA2508624A1/en not_active Abandoned
- 2003-12-18 AU AU2003288856A patent/AU2003288856B2/en not_active Ceased
- 2003-12-18 CL CL200302678A patent/CL2003002678A1/es unknown
- 2003-12-18 JP JP2005502630A patent/JP2006514107A/ja active Pending
- 2003-12-18 PL PL377768A patent/PL377768A1/pl not_active Application Discontinuation
- 2003-12-18 EP EP03781235A patent/EP1572650A1/en not_active Withdrawn
- 2003-12-18 NZ NZ540780A patent/NZ540780A/en unknown
- 2003-12-18 BR BR0317459-0A patent/BR0317459A/pt not_active IP Right Cessation
- 2003-12-19 TW TW092136170A patent/TW200505856A/zh unknown
- 2003-12-19 UY UY28139A patent/UY28139A1/es unknown
-
2005
- 2005-06-13 CO CO05057099A patent/CO5570665A2/es not_active Application Discontinuation
- 2005-07-18 IS IS7942A patent/IS7942A/is unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CL2003002678A1 (es) | 2005-04-22 |
| TW200505856A (en) | 2005-02-16 |
| EP1572650A1 (en) | 2005-09-14 |
| AU2003288856A1 (en) | 2004-07-14 |
| UY28139A1 (es) | 2004-07-30 |
| CA2508624A1 (en) | 2004-07-08 |
| AR042628A1 (es) | 2005-06-29 |
| PL377768A1 (pl) | 2006-02-20 |
| KR20050084424A (ko) | 2005-08-26 |
| WO2004056773A1 (en) | 2004-07-08 |
| MXPA05006381A (es) | 2005-08-29 |
| US20060189650A1 (en) | 2006-08-24 |
| AU2003288856B2 (en) | 2006-11-16 |
| CO5570665A2 (es) | 2005-10-31 |
| IS7942A (is) | 2005-07-18 |
| NZ540780A (en) | 2008-04-30 |
| JP2006514107A (ja) | 2006-04-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
Free format text: REFERENTE A 6A, 7A E 8A ANUIDADE(S). |
|
| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
Free format text: REFERENTE AO DESPACHO 8.6 PUBLICADO NA RPI 2144 DE 07/02/2012. |