BRPI0617987A2 - composição, composição farmacêutica, forma de dosagem efervescente, composição farmacêutica oral de comprimidos unitários múltiplos, forma de dosagem farmacêutica de liberação prolongada, forma de dosagem farmacêutica revestida entérica, forma de dosagem farmacêutica estável para administração oral a sujeitos mamìferos, método para tratamento de doenças relacionadas a ácido gástrico pela inibição de secreção de ácido gástrico, método para tratamento de uma infecção bacteriana provocada ou mediada por helicobacter pylori, processo para preparar um composto da fórmula 3, processo para preparar um composto da fórmula 5, uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de doenças relacionadas a ácido gástrico, pela inibição de secreção de ácido gástrico, uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de uma infecção bacteriana provocada ou mediada por helicobacter pylori uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de doenças relecionadas a ácido gástrico pela inibição de secreção de ácido gástrico - Google Patents
composição, composição farmacêutica, forma de dosagem efervescente, composição farmacêutica oral de comprimidos unitários múltiplos, forma de dosagem farmacêutica de liberação prolongada, forma de dosagem farmacêutica revestida entérica, forma de dosagem farmacêutica estável para administração oral a sujeitos mamìferos, método para tratamento de doenças relacionadas a ácido gástrico pela inibição de secreção de ácido gástrico, método para tratamento de uma infecção bacteriana provocada ou mediada por helicobacter pylori, processo para preparar um composto da fórmula 3, processo para preparar um composto da fórmula 5, uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de doenças relacionadas a ácido gástrico, pela inibição de secreção de ácido gástrico, uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de uma infecção bacteriana provocada ou mediada por helicobacter pylori uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de doenças relecionadas a ácido gástrico pela inibição de secreção de ácido gástrico Download PDFInfo
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- BRPI0617987A2 BRPI0617987A2 BRPI0617987-8A BRPI0617987A BRPI0617987A2 BR PI0617987 A2 BRPI0617987 A2 BR PI0617987A2 BR PI0617987 A BRPI0617987 A BR PI0617987A BR PI0617987 A2 BRPI0617987 A2 BR PI0617987A2
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- enantiomer
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- deuterium
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- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-O triphenylphosphanium Chemical compound C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-O 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- XWNXEWLCHSLQOI-UHFFFAOYSA-K trisodium;triacetate Chemical compound [Na+].[Na+].[Na+].CC([O-])=O.CC([O-])=O.CC([O-])=O XWNXEWLCHSLQOI-UHFFFAOYSA-K 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 230000005641 tunneling Effects 0.000 description 1
- 238000007514 turning Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 125000005065 undecenyl group Chemical group C(=CCCCCCCCCC)* 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000002601 urease inhibitor Substances 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- HQYCOEXWFMFWLR-UHFFFAOYSA-K vanadium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[V+3] HQYCOEXWFMFWLR-UHFFFAOYSA-K 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 238000005051 zero-point vibrational energy Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Substances [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 description 1
- ZMLPZCGHASSGEA-UHFFFAOYSA-M zinc trifluoromethanesulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)C(F)(F)F ZMLPZCGHASSGEA-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- 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
-
- 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
- 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
-
- 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
- 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
- A61P31/04—Antibacterial agents
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72416005P | 2005-10-06 | 2005-10-06 | |
| US60/724,160 | 2005-10-06 | ||
| US74131605P | 2005-12-01 | 2005-12-01 | |
| US60/741,316 | 2005-12-01 | ||
| PCT/US2006/038819 WO2007041630A1 (en) | 2005-10-06 | 2006-10-04 | Deuterated inhibitors of gastric h+, k+-atpase with enhanced therapeutic properties |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0617987A2 true BRPI0617987A2 (pt) | 2011-08-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0617987-8A BRPI0617987A2 (pt) | 2005-10-06 | 2006-10-04 | composição, composição farmacêutica, forma de dosagem efervescente, composição farmacêutica oral de comprimidos unitários múltiplos, forma de dosagem farmacêutica de liberação prolongada, forma de dosagem farmacêutica revestida entérica, forma de dosagem farmacêutica estável para administração oral a sujeitos mamìferos, método para tratamento de doenças relacionadas a ácido gástrico pela inibição de secreção de ácido gástrico, método para tratamento de uma infecção bacteriana provocada ou mediada por helicobacter pylori, processo para preparar um composto da fórmula 3, processo para preparar um composto da fórmula 5, uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de doenças relacionadas a ácido gástrico, pela inibição de secreção de ácido gástrico, uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de uma infecção bacteriana provocada ou mediada por helicobacter pylori uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de doenças relecionadas a ácido gástrico pela inibição de secreção de ácido gástrico |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US7598273B2 (enExample) |
| EP (1) | EP1934201A1 (enExample) |
| JP (1) | JP2009511481A (enExample) |
| CN (1) | CN101309917B (enExample) |
| AU (1) | AU2006299424A1 (enExample) |
| BR (1) | BRPI0617987A2 (enExample) |
| CA (1) | CA2624179A1 (enExample) |
| IL (1) | IL190331A0 (enExample) |
| WO (1) | WO2007041630A1 (enExample) |
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| US7683177B2 (en) * | 2003-06-10 | 2010-03-23 | Teva Pharmaceutical Industries Ltd | Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole |
| US7601737B2 (en) * | 2005-07-26 | 2009-10-13 | Nycomed Gmbh | Isotopically substituted proton pump inhibitors |
| JP5301991B2 (ja) * | 2005-07-29 | 2013-09-25 | コンサート ファーマシューティカルズ インコーポレイテッド | 新規なベンゾ[d][1,3]−ジオキソール誘導体 |
| US7863274B2 (en) * | 2005-07-29 | 2011-01-04 | Concert Pharmaceuticals Inc. | Deuterium enriched analogues of tadalafil as PDE5 inhibitors |
| CA2624179A1 (en) * | 2005-10-06 | 2007-04-12 | Auspex Pharmaceuticals, Inc. | Deuterated inhibitors of gastric h+, k+-atpase with enhanced therapeutic properties |
| US20100076087A1 (en) * | 2005-10-06 | 2010-03-25 | Auspex Pharmaceuticals, Inc. | Methods of reduction of interpatient variability |
| EP2194039A1 (en) * | 2006-03-16 | 2010-06-09 | Vertex Pharmceuticals Incorporated | Process for preparing optically enriched compounds |
| WO2007140189A2 (en) * | 2006-05-26 | 2007-12-06 | Auspex Pharmaceuticals, Inc. | Preparation and utility of substituted carboxylic acid compounds |
| WO2008024439A2 (en) * | 2006-08-22 | 2008-02-28 | Concert Pharmaceuticals Inc. | 4-aminoquinazoline derivatives and methods of use thereof |
| US20110053964A1 (en) * | 2006-08-22 | 2011-03-03 | Roger Tung | 4-aminoquinazoline derivatives and methods of use thereof |
| JP2010507593A (ja) * | 2006-10-20 | 2010-03-11 | コンサート ファーマシューティカルズ インコーポレイテッド | 3−(ジヒドロ−1H−ピラゾロ[4,3−d]ピリミジン−5−イル)−4−プロポキシベンゼンスルホンアミド誘導体および使用方法 |
| US20090197899A1 (en) * | 2006-10-20 | 2009-08-06 | Concert Pharmaceuticals Inc. | 3-(Dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxybenzenesulfonamide Derivatives and Methods of Use |
| US20080280927A1 (en) * | 2006-10-20 | 2008-11-13 | Concert Pharmaceuticals Inc. | 3-(dihydro-1h-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxybenzenesulfonamide derivatives and methods of use |
| US20090270425A1 (en) * | 2006-10-20 | 2009-10-29 | Concert Pharmaceuticals Inc. | 3-(dihydro-1h-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxybenzenesulfonamide derivatives and methods of use |
| WO2008066620A2 (en) * | 2006-10-20 | 2008-06-05 | Concert Pharmaceuticals Inc. | Dibenzothiazepine derivatives |
| US8796267B2 (en) | 2006-10-23 | 2014-08-05 | Concert Pharmaceuticals, Inc. | Oxazolidinone derivatives and methods of use |
| EP2099299A4 (en) * | 2006-10-23 | 2011-11-30 | Concert Pharmaceuticals Inc | OXAZOLIDINONE DERIVATIVES AND METHOD FOR THEIR USE |
| WO2008063600A2 (en) * | 2006-11-17 | 2008-05-29 | Concert Pharmaceuticals Inc. | Triazolyl tropane derivatives |
| US20100260674A1 (en) * | 2006-12-15 | 2010-10-14 | Concert Pharmaceuticals, Inc. | Quinazoline derivatives and methods of treatment |
| US8343950B2 (en) * | 2006-12-15 | 2013-01-01 | Concert Pharmaceuticals, Inc. | Quinazoline derivatives and methods of treatment |
| US20090325976A1 (en) * | 2006-12-21 | 2009-12-31 | Concert Pharmaceuticals Inc. | Prostacyclin derivatives |
| US8080549B2 (en) * | 2007-01-12 | 2011-12-20 | Concert Pharmaceuticals, Inc. | Endothelin receptor antagonists |
| US8071596B2 (en) * | 2007-01-12 | 2011-12-06 | Concert Pharmaceuticals, Inc. | Endothelin receptor antagonists |
| EP2118073A2 (en) * | 2007-02-02 | 2009-11-18 | Concert Pharmaceuticals Inc. | Selective endothelin type-a antagonists |
| US20100076010A1 (en) * | 2007-02-26 | 2010-03-25 | Concert Pharmaceuticals, Inc. | Alpha 1a-adrenoceptor antagonists |
| EP2125717B1 (en) * | 2007-02-26 | 2013-07-03 | Concert Pharmaceuticals Inc. | Deuterated derivatives of silodosin as alpha ia-adrenoreceptor antagonists |
| ATE509015T1 (de) * | 2007-03-07 | 2011-05-15 | Concert Pharmaceuticals Inc | Deuterierte piperazinderivate als verbindungen gegen angina |
| US8759383B2 (en) | 2007-03-16 | 2014-06-24 | Concert Pharmaceuticals, Inc. | Inhibitors of cholesterol ester transfer protein |
| WO2008127640A2 (en) * | 2007-04-11 | 2008-10-23 | Auspex Pharmaceuticals, Inc. | Substituted benzimidazoles |
| WO2008130863A2 (en) * | 2007-04-11 | 2008-10-30 | Auspex Pharmaceuticals, Inc. | Substituted benzimidazoles |
| US8198305B2 (en) * | 2007-04-13 | 2012-06-12 | Concert Pharmaceuticals Inc. | 1,2-benzisoxazol-3-yl compounds |
| US8349817B2 (en) | 2007-04-25 | 2013-01-08 | Concert Pharmaceuticals, Inc. | Analogues of cilostazol |
| ES2401914T3 (es) | 2007-04-25 | 2013-04-25 | Concert Pharmaceuticals Inc. | Análogos de Cilostazol |
| US7608737B2 (en) * | 2007-05-01 | 2009-10-27 | Concert Pharmaceuticasl Inc. | Naphthyl(ethyl)acetamides |
| EP3093290B1 (en) | 2007-05-01 | 2018-01-24 | Concert Pharmaceuticals Inc. | Morphinan compounds |
| ES2401892T3 (es) | 2007-05-01 | 2013-04-25 | Concert Pharmaceuticals Inc. | Compuestos morfinanos |
| US7820666B2 (en) * | 2007-05-08 | 2010-10-26 | Concert Pharmaceuticals, Inc. | Tetrahydrotriazolopyrazine derivatives and uses thereof |
| US20080306151A1 (en) * | 2007-06-11 | 2008-12-11 | Protia, Llc | Deuterium-enriched fenofibrate |
| SI2003120T1 (sl) | 2007-06-12 | 2010-03-31 | Concert Pharmaceuticals Inc | Azapeptidni derivati kot inhibitorji hiv proteaze |
| CA2690379A1 (en) * | 2007-06-13 | 2008-12-24 | Auspex Pharmaceuticals, Inc. | Substituted piperazines |
| US20090005366A1 (en) * | 2007-06-19 | 2009-01-01 | Protia, Llc | Deuterium-enriched olanzapine |
| US20080318920A1 (en) * | 2007-06-19 | 2008-12-25 | Protia, Llc | Deuterium-enriched ezetimibe |
| US7915309B2 (en) * | 2007-06-20 | 2011-03-29 | Protia, Llc | Deuterium-enriched oseltamivir |
| US20080319007A1 (en) * | 2007-06-21 | 2008-12-25 | Protia, Llc | Deuterium-enriched montelukast |
| US7687509B2 (en) * | 2007-07-09 | 2010-03-30 | Concert Pharmaceuticals Inc. | Pyrimidinecarboxamide derivatives |
| CN101821260B (zh) | 2007-08-14 | 2013-07-31 | 康塞特医药品有限公司 | 取代的噁唑烷酮衍生物 |
| US20090062283A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched linezolid |
| US20090062393A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched pregabalin |
| US20090062305A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched cetirizine |
| US20090062316A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched pelitrexol |
| US20090062385A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched fesoterodine |
| US20090062399A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched sertraline |
| US20090062561A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched latanoprost |
| US20090062299A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched doxazosin |
| US20090062374A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched lasofoxifene |
| US20090069410A1 (en) * | 2007-09-09 | 2009-03-12 | Protia, Llc | Deuterium-enriched paclitaxel |
| US20090069413A1 (en) * | 2007-09-09 | 2009-03-12 | Protia, Llc | Deuterium-enriched olopatadine |
| WO2009035598A1 (en) * | 2007-09-10 | 2009-03-19 | Concert Pharmaceuticals, Inc. | Deuterated pirfenidone |
| US20090069339A1 (en) * | 2007-09-11 | 2009-03-12 | Protia, Llc | Deuterium-enriched ciprofloxacin |
| US20090069431A1 (en) * | 2007-09-12 | 2009-03-12 | Protia, Llc | Deuterium-enriched milnacipran |
| US8288414B2 (en) | 2007-09-12 | 2012-10-16 | Deuteria Pharmaceuticals, Inc. | Deuterium-enriched lenalidomide |
| EP2197847B1 (en) * | 2007-09-12 | 2012-11-07 | Concert Pharmaceuticals Inc. | Deuterated 4 -oxoquinoline derivative for the treatment of hiv infection |
| US20090076165A1 (en) * | 2007-09-12 | 2009-03-19 | Protia, Llc | Deuterium-enriched memantine |
| US20090076118A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched saxagliptin |
| US20090076010A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched lamotrigine |
| US20090076112A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched eltrombopag |
| US20090076116A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched carvediolo |
| US20090075965A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched amoxicilin |
| US7919516B2 (en) * | 2007-09-13 | 2011-04-05 | Protia, Llc | Deuterium-enriched ondansetron |
| US20090076161A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched bupropion |
| AU2008299921B2 (en) | 2007-09-13 | 2012-03-01 | Concert Pharmaceuticals, Inc. | Synthesis of deuterated catechols and benzo[d][1,3] dioxoles and derivatives thereof |
| US20090076038A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched entecavir |
| US20090075994A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched radafaxine |
| US20090076039A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched valacyclovir |
| US20090076102A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched muraglitazar |
| US20090075991A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched efavirenz |
| US20090076034A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched bms-690514 |
| US20090076148A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched pravastatin |
| US20090076264A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched rivaroxaban |
| US20090075944A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched ibandronate |
| US20090076128A1 (en) * | 2007-09-15 | 2009-03-19 | Protia Llc | Deuterium-enriched topiramate |
| US20090076164A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched tapentadol |
| US20090076028A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched itraconazole |
| US20090076138A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched darunavir |
| US20090076157A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched senicapoc |
| US20090076040A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched valganciclovir |
| US20090076000A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched mycophenolate mofetil |
| US20090076017A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched trabectedin |
| US20090076018A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched ranolazine |
| US20090076163A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched dapoxetine |
| US20090076126A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched enalapril |
| US20090076167A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched tramiprosate |
| US20090076154A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched vorinostat |
| US20090076144A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched bazedoxifene |
| US20090076058A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched finasteride |
| US20090118238A1 (en) * | 2007-09-17 | 2009-05-07 | Protia, Llc | Deuterium-enriched alendronate |
| US20090076027A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched lurasidone |
| US20090076117A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched laropiprant |
| US20090075997A1 (en) * | 2007-09-19 | 2009-03-19 | Protia, Llc | Deuterium-enriched satavaptan |
| US20090076127A1 (en) * | 2007-09-19 | 2009-03-19 | Protia, Llc | Deuterium-enriched larotaxel |
| US20090076159A1 (en) * | 2007-09-19 | 2009-03-19 | Protia, Llc | Deuterium-enriched eplivanserin |
| US20090076011A1 (en) * | 2007-09-19 | 2009-03-19 | Protia, Llc | Deuterium-enriched tirapazamine |
| US20090082462A1 (en) * | 2007-09-25 | 2009-03-26 | Protia, Llc | Deuterium-enriched armodafinil |
| US20090082334A1 (en) * | 2007-09-25 | 2009-03-26 | Protia, Llc | Deuterium-enriched quetiapine |
| US20090082454A1 (en) * | 2007-09-25 | 2009-03-26 | Protia, Llc | Deuterium-enriched disufenton |
| US20090082364A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched levocedtirizine |
| US20090082459A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched guanfacine |
| US8722710B2 (en) | 2007-09-26 | 2014-05-13 | Deuterx, Llc | Deuterium-enriched pioglitazone |
| US20090082363A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched posaconazole |
| US20090082387A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched nvp-bez234 |
| US20090082436A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched rivastigmine |
| US20090082442A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched lubiprostone |
| US20090082335A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched oxcarbazepine |
| US20090082471A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched fingolimod |
| US20090082452A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched lumiracoxib |
| WO2009051747A1 (en) * | 2007-10-15 | 2009-04-23 | Concert Pharmaceuticals, Inc. | Deuterated lorcaserin |
| WO2009051782A1 (en) * | 2007-10-18 | 2009-04-23 | Concert Pharmaceuticals Inc. | Deuterated etravirine |
| US20090149544A1 (en) * | 2007-10-22 | 2009-06-11 | Concert Pharmaceuticals, Inc. | Alpha-aminoamide derivatives |
| AU2008317375B2 (en) * | 2007-10-26 | 2013-02-28 | Concert Pharmaceuticals, Inc. | Deuterated darunavir |
| US8592487B2 (en) * | 2007-10-26 | 2013-11-26 | Concert Pharmaceuticals, Inc. | Deuterated darunavir |
| US20090175824A1 (en) * | 2007-11-20 | 2009-07-09 | Craig Masse | Peptides for the treatment of HCV infections |
| WO2009076373A1 (en) * | 2007-12-10 | 2009-06-18 | Concert Pharmaceuticals Inc. | Heterocyclic kinase inhibitors |
| EP2231155A4 (en) * | 2007-12-18 | 2011-09-14 | Concert Pharmaceuticals Inc | Tetrahydroisoquinoline DERIVATIVES |
| EP2242493B1 (en) * | 2008-01-22 | 2013-06-05 | Concert Pharmaceuticals Inc. | Derivatives of gefitinib |
| US8609673B2 (en) * | 2008-01-22 | 2013-12-17 | Concert Pharmaceuticals, Inc. | Vandetanib derivatives |
| CN101492452B (zh) * | 2008-01-25 | 2010-11-17 | 山东轩竹医药科技有限公司 | 含有二氧杂环庚烷并吡啶的巯基苯并咪唑衍生物 |
| CN101492464B (zh) * | 2008-01-25 | 2011-01-12 | 山东轩竹医药科技有限公司 | 含有二氧杂环庚烷并吡啶的巯基咪唑并吡啶衍生物 |
| WO2009105604A1 (en) * | 2008-02-20 | 2009-08-27 | Auspex Pharmaceuticals, Inc. | Substituted triazolopyridines |
| EP2265334A2 (en) * | 2008-02-29 | 2010-12-29 | Concert Pharmaceuticals, Inc. | Substituted xanthine derivatives |
| CA2715036A1 (en) * | 2008-03-14 | 2009-09-17 | Retrotope, Inc. | Therapies for cancer using isotopically substituted lysine |
| WO2009114814A2 (en) | 2008-03-14 | 2009-09-17 | Retrotope, Inc. | Therapeutic substances that modulate genome methylation |
| JP2011516426A (ja) * | 2008-03-28 | 2011-05-26 | コンサート ファーマシューティカルズ インコーポレイテッド | キナゾリン誘導体および治療方法 |
| JP2011518783A (ja) * | 2008-04-09 | 2011-06-30 | コンサート ファーマシューティカルズ インコーポレイテッド | 3−(2−ヒドロキシ−5−メチルフェニル)−n,n−ジイソプロピル−3−フェニルプロピルアミンの誘導体およびその使用方法 |
| US8367674B2 (en) * | 2008-04-17 | 2013-02-05 | Concert Pharmaceuticals, Inc. | Piperazine derivatives |
| US20110129549A1 (en) * | 2008-04-17 | 2011-06-02 | Liu Julie F | Tricyclic benzo[5,6]cyclohepta[1,2-b]pyridine derivatives and uses thereof |
| US20100120786A1 (en) * | 2008-04-17 | 2010-05-13 | Concert Pharmaceuticals, Inc. | Piperazine Derivatives |
| WO2009146310A1 (en) * | 2008-05-28 | 2009-12-03 | Concert Pharmaceuticals Inc. | Deuterated tizanidine |
| US8354557B2 (en) * | 2008-06-17 | 2013-01-15 | Concert Pharmaceuticals, Inc. | Synthesis of deuterated morpholine derivatives |
| US9061060B2 (en) | 2008-07-15 | 2015-06-23 | Theracos Inc. | Deuterated benzylbenzene derivatives and methods of use |
| US20100093758A1 (en) * | 2008-07-23 | 2010-04-15 | Auspex Pharmaceuticals, Inc. | Pyridine sulfonamide modulators of endothelin-a receptor |
| US20100221221A1 (en) * | 2008-08-12 | 2010-09-02 | Concert Pharmaceuticals Inc. | N-phenyl-2-pyrimidineamine derivatives |
| PL2328414T3 (pl) | 2008-08-29 | 2014-05-30 | Concert Pharmaceuticals Inc | Podstawione pochodne triazolo-pirydazyny |
| US8541419B2 (en) * | 2008-09-02 | 2013-09-24 | Actimis Pharmaceuticals, Inc. | Isotopically enriched pyrimidin-5-yl acetic acid derivatives as CRTH2 antagonists |
| CA2736091A1 (en) * | 2008-09-03 | 2010-03-11 | Teva Pharmaceutical Industries Ltd. | 2-oxo-1,2-dihydro-quinoline modulators of immune function |
| US20100105755A1 (en) * | 2008-09-12 | 2010-04-29 | Auspex Pharmaceuticals, Inc. | Substituted benzamide modulators of dopamine receptor |
| EP2334621A1 (en) * | 2008-09-16 | 2011-06-22 | Concert Pharmaceuticals, Inc. | Deuterated 2-amino-3-hydroxypropanoic acid derivatives |
| WO2010033270A1 (en) * | 2008-09-17 | 2010-03-25 | Auspex Pharmaceuticals, Inc. | Dibenzothiazepine modulators of dopamine, alpha adrenergic, and serotonin receptors |
| ES2750825T3 (es) | 2008-09-19 | 2020-03-27 | Concert Pharmaceuticals Inc | Compuestos de morfinano deuterados |
| US20100087455A1 (en) * | 2008-10-06 | 2010-04-08 | Auspex Pharmaceuticals, Inc. | Substituted xanthine compounds |
| JP5706825B2 (ja) | 2008-10-17 | 2015-04-22 | シグネーチャー セラピューティクス, インク.Signature Therapeutics, Inc. | フェノール性オピオイドの放出が減弱された医薬組成物 |
| US20100099701A1 (en) * | 2008-10-20 | 2010-04-22 | Auspex Pharmaceuticals, Inc. | Isoquinolinone modulators of 5-ht3 receptors |
| US9045453B2 (en) | 2008-11-14 | 2015-06-02 | Concert Pharmaceuticals, Inc. | Substituted dioxopiperidinyl phthalimide derivatives |
| US20100137215A1 (en) * | 2008-11-25 | 2010-06-03 | Concert Pharmaceuticals Inc. | Novel tetrahydro-1h-pyrido[4,3-b]indoles |
| WO2010065755A1 (en) * | 2008-12-04 | 2010-06-10 | Concert Pharmaceuticals, Inc. | Deuterated pyridinones |
| US20100143354A1 (en) * | 2008-12-04 | 2010-06-10 | Auspex Pharmaceuticals, Inc. | Triazine dna modifiers |
| US20100144657A1 (en) * | 2008-12-09 | 2010-06-10 | Auspex Pharmaceuticals, Inc. | PHENYLPIPERIDINE MODULATORS OF mu-OPIOID RECEPTORS |
| WO2010075086A2 (en) * | 2008-12-15 | 2010-07-01 | Auspex Pharmaceuticals, Inc. | Pyrrolidinone inhibitors of pde-4 |
| US8765953B2 (en) * | 2008-12-23 | 2014-07-01 | Aquilus Pharmaceuticals, Inc. | Compounds and methods for the treatment of pain and other diseases |
| EP2396312A1 (en) * | 2009-02-11 | 2011-12-21 | Celgene Corporation | Isotopologues of lenalidomide |
| US8263601B2 (en) | 2009-02-27 | 2012-09-11 | Concert Pharmaceuticals, Inc. | Deuterium substituted xanthine derivatives |
| US20110053961A1 (en) * | 2009-02-27 | 2011-03-03 | Concert Pharmaceuticals, Inc. | Substituted xanthine derivatives |
| US8563554B2 (en) | 2009-03-17 | 2013-10-22 | Concert Pharmaceuticals, Inc. | Deuterated pyrazinoisoquinoline compounds |
| US8778998B2 (en) * | 2009-04-10 | 2014-07-15 | Auspex Pharmaceuticals, Inc. | Biphenyl-3-carboxylic acid modulators of beta-3-adrenoreceptor |
| US20100291151A1 (en) * | 2009-04-21 | 2010-11-18 | Auspex Pharmaceuticals, Inc. | 1-methylpyrazole modulators of substance p, calcitonin gene-related peptide, adrenergic receptor, and/or 5-ht receptor |
| BRPI1014669A2 (pt) | 2009-04-22 | 2017-07-18 | Axikin Pharmaceuticals Inc | antagonistas ccr3 de arilsulfonamida 2,5-dissubstituída |
| CA2759251C (en) | 2009-04-23 | 2017-01-03 | Concert Pharmaceuticals, Inc. | 4-hydroxybutyric acid analogs |
| US20100305173A1 (en) * | 2009-04-30 | 2010-12-02 | Concert Pharmaceuticals, Inc. | Hydroxyethylamino sulfonamide derivatives |
| US9468637B2 (en) | 2009-05-13 | 2016-10-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2010135579A1 (en) | 2009-05-22 | 2010-11-25 | Concert Pharmaceuticals, Inc. | Fluorinated diaryl urea derivatives |
| CN102459180B (zh) * | 2009-06-09 | 2014-05-14 | 江苏迈度药物研发有限公司 | 作为激酶抑制剂的脲衍生物 |
| EP3090999A1 (en) | 2009-06-18 | 2016-11-09 | Concert Pharmaceuticals Inc. | Deuterated isoindoline-1, 3-dione derivatives as pde4 and tnf-alpha inhibitors |
| EP2454259A1 (en) * | 2009-06-23 | 2012-05-23 | Concert Pharmaceuticals Inc. | Deuterium-modified triazolo-pyridazine derivatives as gaba-a receptor modulators |
| CA2768368A1 (en) * | 2009-07-17 | 2011-01-20 | Rigel Pharmaceuticals, Inc. | Deuterated 2, 4-pyrimidinediamine compounds and prodrugs thereof and their uses |
| WO2011011712A1 (en) * | 2009-07-24 | 2011-01-27 | Concert Pharmaceuticals, Inc. | Substituted imidazotriazines |
| US9512104B2 (en) | 2009-07-28 | 2016-12-06 | Auspex Pharmaceuticals, Inc. | Quinolone inhibitors of lipoprotein-associated phospholipase A2 |
| US8575348B2 (en) * | 2009-07-28 | 2013-11-05 | Auspex Pharmaceuticals, Inc | Quinolone inhibitors of lipoprotein-associated phospholipase A2 |
| US8637524B2 (en) * | 2009-07-28 | 2014-01-28 | Auspex Pharmaceuticals, Inc | Pyrimidinone inhibitors of lipoprotein-associated phospholipase A2 |
| US8618116B2 (en) * | 2009-08-03 | 2013-12-31 | Daljit Singh Dhanoa | Deuterium-enriched pyrimidine compounds and derivatives |
| WO2011020044A1 (en) * | 2009-08-14 | 2011-02-17 | Concert Pharmaceuticals, Inc. | Substituted triazolophthalazine derivatives |
| US8658236B2 (en) | 2009-08-21 | 2014-02-25 | Deuteria Beverages, Llc | Alcoholic compositions having a lowered risk of acetaldehydemia |
| EP2473052A4 (en) * | 2009-09-02 | 2013-03-20 | Concert Pharmaceuticals Inc | SUBSTITUTED XANTHINE DERIVATIVES |
| WO2011028820A1 (en) | 2009-09-02 | 2011-03-10 | Concert Pharmaceuticals, Inc. | Substituted derivatives of bicyclic [4.3.0] heteroaryl compounds |
| BR112012005124B1 (pt) | 2009-09-08 | 2021-11-09 | Signature Therapeutics, Inc. | Pro-fármaco de opioide modificado por cetona, seu método de preparação, sua composição farmacêutica, sua unidade de dose, métodos e usos |
| US20120301463A1 (en) | 2009-09-30 | 2012-11-29 | President And Fellows Of Harvard College | Methods for Modulation of Autophagy Through the Modulation of Autophagy-Enhancing Gene Products |
| WO2011047315A1 (en) * | 2009-10-15 | 2011-04-21 | Concert Pharmaceuticals, Inc. | Subsitituted benzimidazoles |
| KR20120092142A (ko) * | 2009-10-28 | 2012-08-20 | 애나디스 파마슈티칼스, 인코포레이티드 | 중수소화 5,6-다이하이드로-1h-파이리딘-2-온 화합물 |
| WO2011060112A1 (en) | 2009-11-12 | 2011-05-19 | Osi Pharmaceuticals, Inc. | Deuterated tyrosine kinase inhibitors |
| US8471034B2 (en) * | 2009-11-18 | 2013-06-25 | Concert Pharmaceuticals, Inc. | Niacin prodrugs and deuterated versions thereof |
| EP2501679A1 (en) * | 2009-11-21 | 2012-09-26 | F. Hoffmann-La Roche AG | Heterocyclic antiviral compounds |
| US20110178180A1 (en) * | 2010-01-18 | 2011-07-21 | Kurt Nielsen | Deuterium-enriched colchicine, thiocolchicine, and derivatives thereof; methods of preparation; and use thereof |
| UY33226A (es) * | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina deuterada como inhibidores de la cdk4/6 |
| US20110206661A1 (en) * | 2010-02-24 | 2011-08-25 | Auspex Pharmaceuticals, Inc. | Trimethoxyphenyl inhibitors of tyrosine kinase |
| CA2790707A1 (en) * | 2010-03-01 | 2011-09-09 | Concert Pharmaceuticals Inc. | Fluorouracil derivatives |
| US8575361B2 (en) | 2010-03-02 | 2013-11-05 | Concert Pharmaceuticals Inc. | Tetrahydronaphthalene derivatives |
| WO2011109464A1 (en) * | 2010-03-02 | 2011-09-09 | Concert Pharmaceuticals Inc. | Deuterated tetrahydronaphthalene derivatives |
| WO2011116066A1 (en) | 2010-03-17 | 2011-09-22 | Concert Pharmaceuticals, Inc. | Derivatives of dimethylcurcumin |
| ES2710617T3 (es) | 2010-04-21 | 2019-04-26 | Signature Therapeutics Inc | Composiciones que comprenden profármacos de anfetamina escindibles enzimáticamente e inhibidores de los mismos |
| WO2011133178A1 (en) | 2010-04-21 | 2011-10-27 | Pharmacofore, Inc | Compositions comprising enzyme-cleavable phenol-modified tapentadol prodrug |
| WO2011133150A1 (en) * | 2010-04-21 | 2011-10-27 | Pharmacofore, Inc. | Compositions comprising enzyme-cleavable prodrugs of active agents and inhibitors thereof |
| US20110262355A1 (en) | 2010-04-21 | 2011-10-27 | Jenkins Thomas E | Compositions comprising enzyme-cleavable opioid prodrugs and inhibitors thereof |
| BR112012026768A2 (pt) * | 2010-04-21 | 2015-09-29 | Signature Therapeutics Inc | composições compreendendo pró-farmacos de opioides cliváveis de modo enzimático e seus inibidores. |
| WO2012009446A1 (en) | 2010-07-16 | 2012-01-19 | Concert Pharmaceuticals Inc. | Novel pyrimidinecarboxamide derivatives |
| US9085788B2 (en) | 2010-09-01 | 2015-07-21 | Concert Pharmaceuticals, Inc. | Process for preparing an enantiomerically enriched, deuterated secondary alcohol from a corresponding ketone without reducing deuterium incorporation |
| WO2012031073A1 (en) | 2010-09-01 | 2012-03-08 | Concert Pharmaceuticals, Inc. | Process for preparing an enantiomerically enriched, deuterated secondary alcohol from a corresponding ketone without reducing deuterium incorporation |
| AU2011298382A1 (en) * | 2010-09-03 | 2013-05-02 | Teva Pharmaceuticals International Gmbh | Deuterated analogs of pridopidine useful as dopaminergic stabilizers |
| BR112013017296B1 (pt) | 2011-01-11 | 2021-02-17 | Signature Therapeutics, Inc. | composto e composição compreendendo oxicodona, método para reduzir o abuso potencial da referida composição, unidade de dose e método para a sua preparação, e método para identificar um composto e um inibidor de tripsina |
| WO2012096886A1 (en) | 2011-01-11 | 2012-07-19 | Signature Therapeutics, Inc. | Compositions comprising enzyme-cleavable oxycodone prodrug |
| US20130310396A1 (en) * | 2011-01-19 | 2013-11-21 | Hongwen Zhu | Thiazolidine derivatives and their therapeutic use |
| US8759394B2 (en) | 2011-02-14 | 2014-06-24 | Concert Pharmaceuticals, Inc. | 4-hydroxybutyric acid analogs |
| US9145390B2 (en) | 2011-03-03 | 2015-09-29 | Concert Pharmaceuticals, Inc. | Derivatives of pyrazole-substituted amino-heteroaryl compounds |
| US8889687B2 (en) | 2011-03-04 | 2014-11-18 | Concert Pharmaceuticals, Inc. | Deuterated pyrazinoisoquinoline compounds |
| JP6148182B2 (ja) | 2011-03-09 | 2017-06-14 | シグネーチャー セラピューティクス, インク.Signature Therapeutics, Inc. | 複素環式リンカーを有する活性薬剤プロドラッグ |
| WO2012122420A2 (en) | 2011-03-09 | 2012-09-13 | Pharmacofore, Inc. | Opioid prodrugs with heterocyclic linkers |
| AU2012236655B2 (en) | 2011-03-28 | 2016-09-22 | Deuterx, Llc, | 2',6'-dioxo-3'-deutero-piperdin-3-yl-isoindoline compounds |
| US20140213553A1 (en) * | 2011-05-03 | 2014-07-31 | Concert Pharmaceuticals Inc. | Carbamoylpyridone derivatives |
| AU2012250776B2 (en) * | 2011-05-04 | 2017-06-15 | Balance Therapeutics, Inc. | Pentylenetetrazole derivatives |
| HUE047354T2 (hu) | 2011-05-18 | 2020-04-28 | Vertex Pharmaceuticals Europe Ltd | Ivacaftor deuterizált származékai |
| JP6386382B2 (ja) * | 2012-02-08 | 2018-09-05 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | 卵胞刺激ホルモン受容体のアゴニストとしての重水素化されたチアゾリジノン類似体 |
| CN104364255A (zh) | 2012-04-13 | 2015-02-18 | 康塞特医药品有限公司 | 取代的黄嘌呤衍生物 |
| WO2013159026A1 (en) | 2012-04-20 | 2013-10-24 | Concert Pharmaceuticals, Inc. | Deuterated rigosertib |
| SMT202500302T1 (it) * | 2012-06-15 | 2025-09-12 | Sun Pharmaceutical Industries Inc | Derivati deuterati del ruxolitinib |
| US9181190B2 (en) | 2012-07-04 | 2015-11-10 | Concert Pharmaceuticals, Inc. | Deuterated vercirnon |
| EP2885267B1 (en) | 2012-07-12 | 2018-09-05 | Concert Pharmaceuticals, Inc. | Deuterated idebenone |
| IN2015DN00598A (enExample) | 2012-07-30 | 2015-06-26 | Concert Pharmaceuticals Inc | |
| ES2717279T3 (es) | 2012-08-17 | 2019-06-20 | Concert Pharmaceuticals Inc | Baricitinib deuterada |
| US20150210624A1 (en) * | 2012-08-22 | 2015-07-30 | Concert Pharmaceuticals, Inc. | Deuterated 4-hydroxybutyric acid analogs |
| US9682952B2 (en) | 2012-09-04 | 2017-06-20 | Celgene Corporation | Isotopologues of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl) piperidine-2-6-dione and methods of preparation thereof |
| KR20150053906A (ko) * | 2012-09-07 | 2015-05-19 | 액시킨 파마수티컬스 인코포레이티드 | 동위원소 농축 아릴설폰아미드 ccr3 길항제 |
| WO2014066243A1 (en) | 2012-10-22 | 2014-05-01 | Concert Pharmaceuticals, Inc. | Solid forms of {s-3-(4-amino-1-oxo-isoindolin-2yl)(piperidine-3,4,4,5,5-d5)-2,6-dione} |
| EP2943489B1 (en) | 2013-01-09 | 2018-04-11 | Concert Pharmaceuticals Inc. | Deuterated momelotinib |
| CA2935495C (en) | 2013-01-14 | 2021-04-20 | Deuterx, Llc | 3-(5-substituted-4-oxoquinazolin-3(4h)-yl)-3-deutero-piperidine-2,6-dione derivatives |
| WO2014121036A1 (en) * | 2013-02-01 | 2014-08-07 | Deuterx, Llc | 5-deutero-2,4-thiazolidinedione and 5-deutero-2,4-oxazolidinedione derivatives and compositions comprising and methods of using the same |
| US9801882B2 (en) | 2013-02-17 | 2017-10-31 | Intra-Cellular Therapies, Inc. | Phosphodiesterase-1 inhibitors and their use in treatment of cardiovascular diseases |
| EP2968334A4 (en) | 2013-03-14 | 2016-08-03 | Deuterx Llc | 3- (SUBSTITIERTES-4-OXO-quinazolin-3 (4H) -yl) -3-deutero-PIPERIDINE-2,6-DIONE DERIVATIVES |
| AU2014236510A1 (en) | 2013-03-14 | 2015-09-24 | Deuterx, Llc | Deuterium-enriched 2,4-thiazolidinediones and methods of treatment |
| WO2014150043A1 (en) | 2013-03-15 | 2014-09-25 | Concert Pharmaceuticals Inc. | Inhibitors of the enzyme udp-glucose: n-acyl-sphingosine glucosyltransferase |
| CN103204819B (zh) * | 2013-04-15 | 2015-03-11 | 公安部物证鉴定中心 | 氘代地西泮及其制备方法 |
| US9676790B2 (en) | 2013-08-30 | 2017-06-13 | Concert Pharmaceuticals, Inc. | Substituted thienotriazolodiazapines |
| EP3076967B1 (en) | 2013-12-03 | 2021-07-28 | Intra-Cellular Therapies, Inc. | Methods for treating residual symptoms of schizophrenia |
| CA2932757C (en) * | 2013-12-06 | 2023-10-31 | Vertex Pharmaceuticals Incorporated | 2-amino-6-fluoro-n-[5-fluoro-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamide compound useful as atr kinase inhibitor, its preparation, different solid forms and radiolabelled derivatives thereof |
| WO2015095713A1 (en) | 2013-12-20 | 2015-06-25 | Deuterx, Llc | Methods of treating neurological and other disorders using enantiopure deuterium-enriched bupropion |
| US10188639B2 (en) | 2014-01-15 | 2019-01-29 | Deuterx, Llc | Methods of treating neurological, metabolic, and other disorders using enantiopure deuterium-enriched pioglitazone |
| MX2016009817A (es) * | 2014-01-27 | 2017-02-28 | Auspex Pharmaceuticals Inc | Inhibidores de benzoquinolina del transportador vesicular de monoaminas 2. |
| EA201691582A1 (ru) | 2014-02-07 | 2017-01-30 | Оспекс Фармасьютикалз, Инк. | Новые фармацевтические препараты |
| CN106459056A (zh) | 2014-02-10 | 2017-02-22 | 康塞特医药品公司 | 经取代的三唑苯二氮卓 |
| US10077267B2 (en) | 2014-04-04 | 2018-09-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US9884872B2 (en) * | 2014-06-20 | 2018-02-06 | Intra-Cellular Therapies, Inc. | Organic compounds |
| ES2745819T3 (es) | 2014-08-07 | 2020-03-03 | Intra Cellular Therapies Inc | Derivados de imidazo[1,2-a]-pirazolo[4,3-e]-pirimidin-4-ona con actividad inhibidora de la PDE1 |
| IL285760B2 (en) * | 2014-09-02 | 2025-03-01 | Bhupinder Singh | Deuterated or a non-deuterated molecule and pharmaceutical formulations |
| US10160778B2 (en) | 2014-10-27 | 2018-12-25 | Concert Pharmaceuticals, Inc. | Pyrimidine phosphonic acid esters |
| CA2966452A1 (en) * | 2014-12-17 | 2016-06-23 | Samuel David Brown | Substituted bicyclic compounds as bromodomain inhibitors |
| CA2975260C (en) | 2015-01-29 | 2024-05-21 | Signal Pharmaceuticals Llc | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
| US10196384B2 (en) | 2015-03-31 | 2019-02-05 | Vertex Pharmaceuticals (Europe) Limited | Deuterated CFTR modulators |
| CA2981365A1 (en) * | 2015-04-02 | 2016-10-06 | Merck Patent Gmbh | Imidazolonylquinolines and the use thereof as atm kinase inhibitors |
| US10683305B2 (en) * | 2015-04-27 | 2020-06-16 | Concert Pharmaceuticals, Inc. | Deuterated OTX-015 |
| CN107698620A (zh) * | 2015-06-23 | 2018-02-16 | 江苏天士力帝益药业有限公司 | 一种氘代噻吩并哌啶衍生物、制备方法及其应用 |
| KR102457316B1 (ko) * | 2015-06-26 | 2022-10-20 | 총킹 디캉 에릴 파마 씨오. 엘티디. | 새로운 5형포스포디에스테라아제 억제제 및 그 용도 |
| US9809603B1 (en) | 2015-08-18 | 2017-11-07 | Deuterx, Llc | Deuterium-enriched isoindolinonyl-piperidinonyl conjugates and oxoquinazolin-3(4H)-yl-piperidinonyl conjugates and methods of treating medical disorders using same |
| WO2017053711A2 (en) | 2015-09-25 | 2017-03-30 | Concert Pharmaceuticals, Inc. | Deuterated cftr potentiators |
| CN107207469B (zh) * | 2015-10-21 | 2018-09-25 | 纽弗姆制药有限公司 | 用于治疗血液恶性肿瘤的氘代化合物以及其组合物和方法 |
| US20200262800A1 (en) * | 2015-11-16 | 2020-08-20 | Ptc Therapeutics, Inc. | Hydrogen isotope-enriched analogues of 1,2,4-oxadiazole benzoic acid compounds, compositions and uses thereof |
| WO2017087795A1 (en) | 2015-11-19 | 2017-05-26 | Concert Pharmaceuticals, Inc. | Deuterated epi-743 |
| RU2743513C2 (ru) | 2016-01-26 | 2021-02-19 | Интра-Селлулар Терапиз, Инк. | Органические соединения |
| CN108541255B (zh) * | 2016-02-02 | 2019-06-14 | 深圳市塔吉瑞生物医药有限公司 | 一种甾体类化合物及包含该化合物的组合物及其用途 |
| US10442761B2 (en) | 2016-02-16 | 2019-10-15 | Concert Pharmaceuticals, Inc. | Deuterated GFT-505 |
| JP6686168B2 (ja) | 2016-03-25 | 2020-04-22 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 有機化合物 |
| JP2019510039A (ja) | 2016-03-28 | 2019-04-11 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 新規組成物および方法 |
| WO2018071233A1 (en) | 2016-10-12 | 2018-04-19 | Intra-Cellular Therapies, Inc. | Amorphous solid dispersions |
| EP3562484B1 (en) | 2016-12-29 | 2021-08-25 | Intra-Cellular Therapies, Inc. | Pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline derivatives useful in the treatment of cns disorders |
| WO2018126140A1 (en) | 2016-12-29 | 2018-07-05 | Intra-Cellular Therapies, Inc. | Organic compounds |
| MX387784B (es) | 2017-03-24 | 2025-03-18 | Intra Celular Therapies Inc | Composiciones novedosas y metodos. |
| WO2018213426A1 (en) * | 2017-05-16 | 2018-11-22 | Vertex Pharmaceuticals Incorporated | Deuterated pyridone amides and prodrugs thereof as modulators of sodium channels |
| CN109498811A (zh) * | 2017-09-15 | 2019-03-22 | 江苏吉贝尔药业股份有限公司 | 一种含钾离子竞争性酸阻滞剂和非甾体抗炎药的复方制剂 |
| JP7518765B2 (ja) | 2017-11-22 | 2024-07-18 | コンサート ファーマシューティカルズ インコーポレイテッド | D-セリンの重水素化類似体およびその使用 |
| CN111479804B (zh) | 2017-12-01 | 2023-12-22 | 弗特克斯药品有限公司 | 用于制备囊性纤维化跨膜传导调节因子的调节剂的方法 |
| US11453672B2 (en) * | 2017-12-22 | 2022-09-27 | Shenzhen Targetrx, Inc. | Substituted pyrazolo[1,5-a]pyrimidines as tropomyosin receptor kinase inhibitors |
| CN111848622A (zh) | 2018-01-23 | 2020-10-30 | 深圳市塔吉瑞生物医药有限公司 | 取代的吡唑并[1,5-a]嘧啶类的大环化合物 |
| EP3746081A4 (en) | 2018-01-31 | 2021-10-27 | Intra-Cellular Therapies, Inc. | Novel uses |
| CN112040940A (zh) | 2018-03-23 | 2020-12-04 | 细胞内治疗公司 | 有机化合物 |
| JP7710223B2 (ja) * | 2018-04-16 | 2025-07-18 | 深▲チェン▼市塔吉瑞生物医薬有限公司 | 置換ピロロトリアジン系化合物およびその医薬組成物並びにそれらの使用 |
| WO2019246085A1 (en) * | 2018-06-19 | 2019-12-26 | Celecor Therapeutics, Inc. | Deuterated ruc-4 |
| EP3816162A4 (en) * | 2018-07-12 | 2021-08-11 | Shenzhen TargetRx, Inc. | DIARYL PYRAZOLE COMPOUND, COMPOSITION THEREOF, AND USE THEREOF |
| WO2020047241A1 (en) | 2018-08-29 | 2020-03-05 | Intra-Cellular Therapies, Inc. | Novel compositions and methods |
| CA3108558A1 (en) | 2018-08-31 | 2020-03-05 | Intra-Cellular Therapies, Inc. | Novel methods |
| EP3843738A4 (en) | 2018-08-31 | 2022-06-01 | Intra-Cellular Therapies, Inc. | NEW METHODS |
| CN108752322A (zh) * | 2018-09-12 | 2018-11-06 | 广州新民培林医药科技有限公司 | 一种新型Tepotinib衍生物和制备方法及其在抗肿瘤药物中的应用 |
| CN118806924A (zh) * | 2018-09-26 | 2024-10-22 | 江苏恒瑞医药股份有限公司 | 依喜替康类似物的配体-药物偶联物及其制备方法和应用 |
| WO2020151605A1 (zh) * | 2019-01-25 | 2020-07-30 | 青岛吉澳医药科技有限公司 | 氘代苯甲氨嘧啶二酮衍生物及其用途 |
| WO2020206367A1 (en) | 2019-04-03 | 2020-10-08 | Concert Pharmaceuticals, Inc. | Processes for the preparation of deuterated d-serine |
| WO2020227491A1 (en) * | 2019-05-07 | 2020-11-12 | The Trustees Of The University Of Pennsylvania | Deuterated triazolopyrimidines |
| CN114072150A (zh) | 2019-07-07 | 2022-02-18 | 细胞内治疗公司 | 新方法 |
| CN110194773B (zh) * | 2019-07-26 | 2019-11-22 | 上海美迪西生物医药股份有限公司 | 吡咯并吡唑类衍生物、其制备方法及其在医药上的应用 |
| WO2021022012A1 (en) * | 2019-07-30 | 2021-02-04 | The Regents Of The University Of California | Methods and composition for treating respiratory obstructive diseases |
| EP4413980A3 (en) * | 2019-09-03 | 2024-10-30 | Intra-Cellular Therapies, Inc. | Novel compounds |
| US11319313B2 (en) | 2020-06-30 | 2022-05-03 | Poxel Sa | Crystalline forms of deuterium-enriched pioglitazone |
| US11767317B1 (en) | 2020-06-30 | 2023-09-26 | Poxel Sa | Methods of synthesizing enantiopure deuterium-enriched pioglitazone |
| MX2024003466A (es) | 2021-09-29 | 2024-06-04 | Ensysce Biosciences Inc | Profarmacos de metadona escindibles por enzimas y metodos de uso de los mismos. |
| WO2023081899A1 (en) * | 2021-11-05 | 2023-05-11 | Terran Biosciences, Inc. | Isotopically enriched n-methyl-1,3-benzodioxolylbutanamine (mbdb) and stereoisomers thereof |
| WO2023092044A2 (en) | 2021-11-17 | 2023-05-25 | Terran Biosciences, Inc. | Phenethylamine compounds salts, polymorphic forms and methods of use thereof |
| TW202325301A (zh) * | 2021-12-14 | 2023-07-01 | 大陸商海思科醫藥集團股份有限公司 | 三環稠雜環類pde3/4雙重抑制及其用途 |
| WO2023147419A2 (en) * | 2022-01-27 | 2023-08-03 | Pmv Pharmaceuticals, Inc. | Deuterated compounds for restoring mutant p53 function |
| CN116726011A (zh) * | 2022-03-04 | 2023-09-12 | 丽珠医药集团股份有限公司 | 艾普拉唑用于调节消化道微生态的用途 |
| US12414948B2 (en) | 2022-05-18 | 2025-09-16 | Intra-Cellular Therapies, Inc. | Methods |
| US12364699B2 (en) | 2023-10-10 | 2025-07-22 | Sun Pharmaceuticals Industries, Inc. | Method of treating hair loss disorders |
Family Cites Families (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE7804231L (sv) | 1978-04-14 | 1979-10-15 | Haessle Ab | Magsyrasekretionsmedel |
| IL75400A (en) * | 1984-06-16 | 1988-10-31 | Byk Gulden Lomberg Chem Fab | Dialkoxypyridine methyl(sulfinyl or sulfonyl)benzimidazoles,processes for the preparation thereof and pharmaceutical compositions containing the same |
| JPS6150978A (ja) * | 1984-08-16 | 1986-03-13 | Takeda Chem Ind Ltd | ピリジン誘導体およびその製造法 |
| US6749864B2 (en) * | 1986-02-13 | 2004-06-15 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| US5433959A (en) * | 1986-02-13 | 1995-07-18 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| CA1327010C (en) * | 1986-02-13 | 1994-02-15 | Tadashi Makino | Stabilized solid pharmaceutical composition containing antiulcer benzimidazole compound and its production |
| US5026560A (en) * | 1987-01-29 | 1991-06-25 | Takeda Chemical Industries, Ltd. | Spherical granules having core and their production |
| ATE114114T1 (de) * | 1989-02-10 | 1994-12-15 | Takeda Chemical Industries Ltd | Verwendung von benzimidazol-derivaten als antibakterielle mittel. |
| YU48263B (sh) * | 1991-06-17 | 1997-09-30 | Byk Gulden Lomberg Chemische Fabrik Gmbh. | Postupak za dobijanje farmaceutskog preparata na bazi pantoprazola |
| US5464632C1 (en) * | 1991-07-22 | 2001-02-20 | Prographarm Lab | Rapidly disintegratable multiparticular tablet |
| US6875872B1 (en) * | 1993-05-28 | 2005-04-05 | Astrazeneca | Compounds |
| US5877192A (en) * | 1993-05-28 | 1999-03-02 | Astra Aktiebolag | Method for the treatment of gastric acid-related diseases and production of medication using (-) enantiomer of omeprazole |
| SE9301830D0 (sv) * | 1993-05-28 | 1993-05-28 | Ab Astra | New compounds |
| SE9302395D0 (sv) * | 1993-07-09 | 1993-07-09 | Ab Astra | New pharmaceutical formulation |
| SE9302396D0 (sv) * | 1993-07-09 | 1993-07-09 | Ab Astra | A novel compound form |
| US6334997B1 (en) * | 1994-03-25 | 2002-01-01 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| JP3696884B2 (ja) | 1994-03-25 | 2005-09-21 | アイソテクニカ、インコーポレーテッド | ジュウテリウム化による薬物の効能の増強 |
| US6221335B1 (en) * | 1994-03-25 | 2001-04-24 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| US5840737A (en) * | 1996-01-04 | 1998-11-24 | The Curators Of The University Of Missouri | Omeprazole solution and method for using same |
| US6489346B1 (en) * | 1996-01-04 | 2002-12-03 | The Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of using same |
| US6645988B2 (en) * | 1996-01-04 | 2003-11-11 | Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of using same |
| US6699885B2 (en) * | 1996-01-04 | 2004-03-02 | The Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and methods of using same |
| SE510650C2 (sv) * | 1997-05-30 | 1999-06-14 | Astra Ab | Ny förening |
| US6884429B2 (en) * | 1997-09-05 | 2005-04-26 | Isotechnika International Inc. | Medical devices incorporating deuterated rapamycin for controlled delivery thereof |
| DE69840586D1 (de) * | 1997-10-08 | 2009-04-02 | Isotechnika Inc | Deuterierte Cyclosporin-analoga und ihre Verwendung als immunmodulierende Agenzien |
| WO1999059544A2 (en) * | 1998-05-18 | 1999-11-25 | Takeda Chemical Industries, Ltd. | Orally disintegrable tablets |
| ATE481090T1 (de) * | 1998-07-28 | 2010-10-15 | Takeda Pharmaceutical | Leicht zerfallende feste zubereitung |
| US6166213A (en) * | 1998-08-11 | 2000-12-26 | Merck & Co., Inc. | Omeprazole process and compositions thereof |
| US6191148B1 (en) * | 1998-08-11 | 2001-02-20 | Merck & Co., Inc. | Omerazole process and compositions thereof |
| SE9803772D0 (sv) * | 1998-11-05 | 1998-11-05 | Astra Ab | Pharmaceutical formulation |
| UA72748C2 (en) * | 1998-11-10 | 2005-04-15 | Astrazeneca Ab | A novel crystalline form of omeprazole |
| US6440710B1 (en) * | 1998-12-10 | 2002-08-27 | The Scripps Research Institute | Antibody-catalyzed deuteration, tritiation, dedeuteration or detritiation of carbonyl compounds |
| NO309305B1 (no) * | 1999-02-19 | 2001-01-15 | Norsk Hydro As | Anvendelse av benzaldehydderivater ved fremstilling av farmasöytiske preparater for forebygging og/eller behandling av kreft, samt visse nye benzaldehydderivater |
| TWI289557B (en) * | 1999-06-17 | 2007-11-11 | Takeda Chemical Industries Ltd | A crystal of a hydrate of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole |
| EP1104760B1 (en) * | 1999-12-03 | 2003-03-12 | Pfizer Products Inc. | Sulfamoylheteroaryl pyrazole compounds as anti-inflammatory/analgesic agents |
| EP1134290A3 (en) * | 2000-03-14 | 2004-01-02 | Pfizer Products Inc. | Pharmacophore models for the identification of the CYP2D6 inhibitory potency of selective serotonin reuptake inhibitors |
| AU2001278755A1 (en) * | 2000-08-18 | 2002-03-04 | Takeda Chemical Industries Ltd. | Injections |
| MY137726A (en) * | 2000-11-22 | 2009-03-31 | Nycomed Gmbh | Freeze-dried pantoprazole preparation and pantoprazole injection |
| TWI290922B (en) * | 2000-12-01 | 2007-12-11 | Takeda Chemical Industries Ltd | Production method of crystals |
| DE10123129A1 (de) * | 2001-05-02 | 2002-11-14 | Berolina Drug Dev Ab Svedala | Deuterierte 3-Piperidinopropiophenone sowie diese Verbindungen enthaltende Arzneimittel |
| DE10162121A1 (de) * | 2001-12-12 | 2003-06-18 | Berolina Drug Dev Ab Svedala | Deuterierte substituierte Pyrazolyl-Benzolsulfonamide sowie diese Verbindungen enthaltende Arzneimittel |
| TW200413273A (en) * | 2002-11-15 | 2004-08-01 | Wako Pure Chem Ind Ltd | Heavy hydrogenation method of heterocyclic rings |
| US7601737B2 (en) * | 2005-07-26 | 2009-10-13 | Nycomed Gmbh | Isotopically substituted proton pump inhibitors |
| BRPI0614039A2 (pt) | 2005-07-26 | 2011-03-09 | Nycomed Gmbh | inibidores isotopicamente substituìdos da bomba de prótons |
| TWI410409B (zh) * | 2005-07-26 | 2013-10-01 | Takeda Gmbh | 同位素取代之潘托拉唑(pantoprazole) |
| US20080033011A1 (en) * | 2005-07-29 | 2008-02-07 | Concert Pharmaceuticals Inc. | Novel benzo[d][1,3]-dioxol derivatives |
| JP2009504798A (ja) | 2005-08-22 | 2009-02-05 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | 同位体置換されたベンゾイミダゾール誘導体 |
| WO2007039464A1 (en) | 2005-09-22 | 2007-04-12 | Nycomed Gmbh | Isotopically substituted imidazopyridine derivatives for the treatment of gastrointestinal disorders |
| CA2624179A1 (en) | 2005-10-06 | 2007-04-12 | Auspex Pharmaceuticals, Inc. | Deuterated inhibitors of gastric h+, k+-atpase with enhanced therapeutic properties |
| US20100076087A1 (en) * | 2005-10-06 | 2010-03-25 | Auspex Pharmaceuticals, Inc. | Methods of reduction of interpatient variability |
| US7750168B2 (en) * | 2006-02-10 | 2010-07-06 | Sigma-Aldrich Co. | Stabilized deuteroborane-tetrahydrofuran complex |
| AU2007256844A1 (en) * | 2006-06-05 | 2007-12-13 | Auspex Pharmaceuticals, Inc. | Preparation and utility of substituted erythromycin analogs |
| WO2008035195A1 (en) | 2006-09-21 | 2008-03-27 | Raqualia Pharma Inc. | Benzimidazole derivatives as selective acid pump inhibitors |
| WO2008114123A1 (en) | 2007-03-21 | 2008-09-25 | Raqualia Pharma Inc. | Spiro benzimidazole derivatives as acid pump inhibitors |
| WO2008127640A2 (en) | 2007-04-11 | 2008-10-23 | Auspex Pharmaceuticals, Inc. | Substituted benzimidazoles |
| WO2008130863A2 (en) | 2007-04-11 | 2008-10-30 | Auspex Pharmaceuticals, Inc. | Substituted benzimidazoles |
| WO2008131259A1 (en) | 2007-04-19 | 2008-10-30 | Concert Pharmaceuticals Inc. | Deuterated morpholinyl compounds |
| US20090076089A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched pantoprazole |
| US20090258897A1 (en) * | 2008-04-11 | 2009-10-15 | Auspex Pharmaceuticals, Inc. | Substituted benzimidazoles |
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| JP2009511481A (ja) | 2009-03-19 |
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| US20090209592A1 (en) | 2009-08-20 |
| CN101309917B (zh) | 2013-09-11 |
| US20090215831A1 (en) | 2009-08-27 |
| WO2007041630A1 (en) | 2007-04-12 |
| IL190331A0 (en) | 2009-09-22 |
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