CN102648179B - 作为趋化因子受体活性调节剂的哌啶基衍生物的前药 - Google Patents
作为趋化因子受体活性调节剂的哌啶基衍生物的前药 Download PDFInfo
- Publication number
- CN102648179B CN102648179B CN201080055421.4A CN201080055421A CN102648179B CN 102648179 B CN102648179 B CN 102648179B CN 201080055421 A CN201080055421 A CN 201080055421A CN 102648179 B CN102648179 B CN 102648179B
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- China
- Prior art keywords
- compound
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- compounds
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- Expired - Fee Related
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- PKOPPWBYAWHOTQ-DZIBYMRMSA-N CC(C)C(C(N(CC1)CC(C)(C)C1c(cc1)ccc1Cl)=O)NC(NC(C)(C)OC([C@H](C)N)=O)=O Chemical compound CC(C)C(C(N(CC1)CC(C)(C)C1c(cc1)ccc1Cl)=O)NC(NC(C)(C)OC([C@H](C)N)=O)=O PKOPPWBYAWHOTQ-DZIBYMRMSA-N 0.000 description 1
- XOLXKHYXCSCYDP-UHFFFAOYSA-N CC(C)C(C(N(CCC12)CC(C)(C)C1C2c(cc1)ccc1Cl)=O)NC(NC(C)(C)OC(OCCN1CCOCC1)=O)=O Chemical compound CC(C)C(C(N(CCC12)CC(C)(C)C1C2c(cc1)ccc1Cl)=O)NC(NC(C)(C)OC(OCCN1CCOCC1)=O)=O XOLXKHYXCSCYDP-UHFFFAOYSA-N 0.000 description 1
- GEKVIJFTZJFBJI-NLFFAJNJSA-N CC(C)[C@H](C(N(CC1)CC(C)(C)[C@]1(c(cc1)ccc1Cl)O)=O)NC(NCC(C)(C)OC(CN)=O)=O Chemical compound CC(C)[C@H](C(N(CC1)CC(C)(C)[C@]1(c(cc1)ccc1Cl)O)=O)NC(NCC(C)(C)OC(CN)=O)=O GEKVIJFTZJFBJI-NLFFAJNJSA-N 0.000 description 1
- SHFJWVFHMDRTFE-DVECYGJZSA-N CC(C)[C@H](C(N(CC1)CC(C)(C)[C@]1(c(cc1)ccc1Cl)O)=O)NC(NCC(C)(C)OCOP(O)(O)=O)=O Chemical compound CC(C)[C@H](C(N(CC1)CC(C)(C)[C@]1(c(cc1)ccc1Cl)O)=O)NC(NCC(C)(C)OCOP(O)(O)=O)=O SHFJWVFHMDRTFE-DVECYGJZSA-N 0.000 description 1
- RKMHBPXLQKASPD-NLFFAJNJSA-N CC(C)[C@H](C(N(CC1)CC(C)(C)[C@]1(c(cc1)ccc1Cl)O)=O)NC(NCC(C)(C)OCSC)=O Chemical compound CC(C)[C@H](C(N(CC1)CC(C)(C)[C@]1(c(cc1)ccc1Cl)O)=O)NC(NCC(C)(C)OCSC)=O RKMHBPXLQKASPD-NLFFAJNJSA-N 0.000 description 1
- NBBGDNBACYHUJN-BXTJHSDWSA-N CC(C)[C@H](C(NCC(C)(C)[C@@]([C@@H]1C(C)=CC1)(O)Cl)=O)NC(NCC(C)(C)O)=O Chemical compound CC(C)[C@H](C(NCC(C)(C)[C@@]([C@@H]1C(C)=CC1)(O)Cl)=O)NC(NCC(C)(C)O)=O NBBGDNBACYHUJN-BXTJHSDWSA-N 0.000 description 1
- GWQZCMFUMDFEMJ-GGDUUVFYSA-N CC(C1C)C1(C(N(CC1)CC(C)(C)[C@]1(c(cc1)ccc1Cl)O)=O)NC(NCC(C)(C)OP(OCc1ccccc1)(OCc1ccccc1)=O)=O Chemical compound CC(C1C)C1(C(N(CC1)CC(C)(C)[C@]1(c(cc1)ccc1Cl)O)=O)NC(NCC(C)(C)OP(OCc1ccccc1)(OCc1ccccc1)=O)=O GWQZCMFUMDFEMJ-GGDUUVFYSA-N 0.000 description 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
- C07D211/36—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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07D211/04—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
-
- 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/59—Hydrogenated pyridine rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Tropical Medicine & Parasitology (AREA)
- Psychiatry (AREA)
- AIDS & HIV (AREA)
- Communicable Diseases (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24927009P | 2009-10-07 | 2009-10-07 | |
| US61/249,270 | 2009-10-07 | ||
| PCT/US2010/051731 WO2011044309A1 (en) | 2009-10-07 | 2010-10-07 | Prodrugs of a piperidinyl derivative as modulators of chemokine receptor activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102648179A CN102648179A (zh) | 2012-08-22 |
| CN102648179B true CN102648179B (zh) | 2015-06-17 |
Family
ID=43334406
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080055421.4A Expired - Fee Related CN102648179B (zh) | 2009-10-07 | 2010-10-07 | 作为趋化因子受体活性调节剂的哌啶基衍生物的前药 |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US8410139B2 (enExample) |
| EP (1) | EP2486013B1 (enExample) |
| JP (1) | JP5788397B2 (enExample) |
| KR (1) | KR20120083900A (enExample) |
| CN (1) | CN102648179B (enExample) |
| AR (1) | AR078543A1 (enExample) |
| AU (1) | AU2010303441A1 (enExample) |
| BR (1) | BR112012007755A2 (enExample) |
| CA (1) | CA2777032A1 (enExample) |
| CL (1) | CL2012000882A1 (enExample) |
| CO (1) | CO6440510A2 (enExample) |
| EA (1) | EA022150B1 (enExample) |
| IL (1) | IL219122A (enExample) |
| MX (1) | MX2012003656A (enExample) |
| NZ (1) | NZ599261A (enExample) |
| PE (1) | PE20121109A1 (enExample) |
| TW (1) | TW201118070A (enExample) |
| WO (1) | WO2011044309A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT3129016T (pt) | 2014-04-08 | 2018-10-01 | Neurovive Pharmaceutical Ab | Compostos novos |
| AR106018A1 (es) * | 2015-08-26 | 2017-12-06 | Achillion Pharmaceuticals Inc | Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos |
| WO2017035409A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Aryl, heteroaryl, and heterocyclic compounds for treatment of immune and inflammatory disorders |
| EP3589287B1 (en) | 2017-03-01 | 2022-09-14 | Achillion Pharmaceuticals, Inc. | Macrocyclic compounds for treatment of medical disorders |
| CN110776481B (zh) * | 2018-07-24 | 2023-06-16 | 四川大学华西医院 | 一类双阳离子化合物及其制备方法和用途 |
| CN108727248B (zh) | 2018-07-25 | 2021-05-25 | 四川大学华西医院 | 一类双季铵化合物及其制备方法和用途 |
| EP3898617A4 (en) | 2018-12-17 | 2022-08-17 | Achillion Pharmaceuticals, Inc. | TARGETED DOSAGE FOR THE TREATMENT OF COMPLEMENT INDUCED DISORDERS |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007092681A2 (en) * | 2006-01-27 | 2007-08-16 | Bristol-Myers Squibb Company | Piperidinyl derivatives as modulators of chemokine receptor activity |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU770042B2 (en) * | 1998-12-18 | 2004-02-12 | Bristol-Myers Squibb Pharma Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| JP2006520783A (ja) * | 2003-03-18 | 2006-09-14 | メルク エンド カムパニー インコーポレーテッド | ケモカイン受容体活性のアミノシクロブチルアミド調節物質 |
| AU2007275931B2 (en) * | 2006-07-19 | 2011-06-16 | Astrazeneca Ab | Novel tricyclic spiropiperidine compounds, their synthesis and their uses as modulators of chemokine receptor activity |
| WO2009015164A2 (en) | 2007-07-24 | 2009-01-29 | Bristol-Myers Squibb Company | Piperidinyl derivatives as modulators of chemokine receptor activity |
| EP2173714B9 (en) | 2007-07-24 | 2013-04-10 | Bristol-Myers Squibb Company | Piperidine derivatives as modulators of chemokine receptor activity |
| TWI433838B (zh) * | 2008-06-25 | 2014-04-11 | 必治妥美雅史谷比公司 | 作為趨化因子受體活性調節劑之六氫吡啶衍生物 |
-
2010
- 2010-10-04 US US12/896,955 patent/US8410139B2/en active Active
- 2010-10-06 AR ARP100103636A patent/AR078543A1/es unknown
- 2010-10-06 TW TW099134093A patent/TW201118070A/zh unknown
- 2010-10-07 KR KR1020127011586A patent/KR20120083900A/ko not_active Withdrawn
- 2010-10-07 CA CA2777032A patent/CA2777032A1/en not_active Abandoned
- 2010-10-07 WO PCT/US2010/051731 patent/WO2011044309A1/en not_active Ceased
- 2010-10-07 NZ NZ599261A patent/NZ599261A/xx not_active IP Right Cessation
- 2010-10-07 MX MX2012003656A patent/MX2012003656A/es active IP Right Grant
- 2010-10-07 JP JP2012533303A patent/JP5788397B2/ja not_active Expired - Fee Related
- 2010-10-07 EP EP10766190.2A patent/EP2486013B1/en not_active Not-in-force
- 2010-10-07 AU AU2010303441A patent/AU2010303441A1/en not_active Abandoned
- 2010-10-07 BR BR112012007755A patent/BR112012007755A2/pt not_active IP Right Cessation
- 2010-10-07 EA EA201270468A patent/EA022150B1/ru not_active IP Right Cessation
- 2010-10-07 CN CN201080055421.4A patent/CN102648179B/zh not_active Expired - Fee Related
- 2010-10-07 PE PE2012000437A patent/PE20121109A1/es not_active Application Discontinuation
-
2012
- 2012-03-29 CO CO12053565A patent/CO6440510A2/es active IP Right Grant
- 2012-04-05 IL IL219122A patent/IL219122A/en not_active IP Right Cessation
- 2012-04-05 CL CL2012000882A patent/CL2012000882A1/es unknown
-
2013
- 2013-03-05 US US13/785,039 patent/US20130178444A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007092681A2 (en) * | 2006-01-27 | 2007-08-16 | Bristol-Myers Squibb Company | Piperidinyl derivatives as modulators of chemokine receptor activity |
Also Published As
| Publication number | Publication date |
|---|---|
| MX2012003656A (es) | 2012-04-30 |
| EA022150B1 (ru) | 2015-11-30 |
| EP2486013B1 (en) | 2015-07-08 |
| CL2012000882A1 (es) | 2012-09-07 |
| NZ599261A (en) | 2013-10-25 |
| EA201270468A1 (ru) | 2012-11-30 |
| AU2010303441A1 (en) | 2012-05-03 |
| CA2777032A1 (en) | 2011-04-14 |
| WO2011044309A1 (en) | 2011-04-14 |
| US20130178444A1 (en) | 2013-07-11 |
| CN102648179A (zh) | 2012-08-22 |
| US20110082113A1 (en) | 2011-04-07 |
| TW201118070A (en) | 2011-06-01 |
| PE20121109A1 (es) | 2012-08-20 |
| US8410139B2 (en) | 2013-04-02 |
| AR078543A1 (es) | 2011-11-16 |
| BR112012007755A2 (pt) | 2015-09-15 |
| KR20120083900A (ko) | 2012-07-26 |
| JP2013507377A (ja) | 2013-03-04 |
| CO6440510A2 (es) | 2012-05-15 |
| EP2486013A1 (en) | 2012-08-15 |
| IL219122A (en) | 2015-04-30 |
| JP5788397B2 (ja) | 2015-09-30 |
| IL219122A0 (en) | 2012-06-28 |
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