CA2624179A1 - Deuterated inhibitors of gastric h+, k+-atpase with enhanced therapeutic properties - Google Patents
Deuterated inhibitors of gastric h+, k+-atpase with enhanced therapeutic properties Download PDFInfo
- Publication number
- CA2624179A1 CA2624179A1 CA002624179A CA2624179A CA2624179A1 CA 2624179 A1 CA2624179 A1 CA 2624179A1 CA 002624179 A CA002624179 A CA 002624179A CA 2624179 A CA2624179 A CA 2624179A CA 2624179 A1 CA2624179 A1 CA 2624179A1
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- Prior art keywords
- enantiomer
- compound
- deuterium
- mixture
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
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- 235000019640 taste Nutrition 0.000 description 1
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- 229960003604 testosterone Drugs 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
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- 150000003522 tetracyclines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
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- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000000858 thiocyanato group Chemical group *SC#N 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 1
- UBZYKBZMAMTNKW-UHFFFAOYSA-J titanium tetrabromide Chemical compound Br[Ti](Br)(Br)Br UBZYKBZMAMTNKW-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- NLLZTRMHNHVXJJ-UHFFFAOYSA-J titanium tetraiodide Chemical compound I[Ti](I)(I)I NLLZTRMHNHVXJJ-UHFFFAOYSA-J 0.000 description 1
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- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- INQOMBQAUSQDDS-FIBGUPNXSA-N trideuterio(iodo)methane Chemical compound [2H]C([2H])([2H])I INQOMBQAUSQDDS-FIBGUPNXSA-N 0.000 description 1
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 description 1
- VOITXYVAKOUIBA-UHFFFAOYSA-N triethylaluminium Chemical compound CC[Al](CC)CC VOITXYVAKOUIBA-UHFFFAOYSA-N 0.000 description 1
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- MJCYPBSRKLJZTB-UHFFFAOYSA-N trifluoroborane;dihydrate Chemical compound O.O.FB(F)F MJCYPBSRKLJZTB-UHFFFAOYSA-N 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
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- 125000005423 trihalomethanesulfonamido group Chemical group 0.000 description 1
- 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
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- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
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- 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
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- 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
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Classifications
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- 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
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- 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 |
|---|---|
| CA2624179A1 true CA2624179A1 (en) | 2007-04-12 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002624179A Abandoned CA2624179A1 (en) | 2005-10-06 | 2006-10-04 | Deuterated inhibitors of gastric h+, k+-atpase with enhanced therapeutic properties |
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 |
| US7863274B2 (en) * | 2005-07-29 | 2011-01-04 | Concert Pharmaceuticals Inc. | Deuterium enriched analogues of tadalafil as PDE5 inhibitors |
| EP1910322B1 (en) * | 2005-07-29 | 2012-09-05 | Concert Pharmaceuticals Inc. | Novel deuterated benzo [d][1,3]-dioxol derivatives as serotonin reuptake 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 |
| NZ571280A (en) * | 2006-03-16 | 2011-10-28 | Vertex Pharma | Deuterated hepatitis C protease inhibitors |
| BRPI0711228A2 (pt) * | 2006-05-26 | 2012-06-19 | Auspex Pharmaceuticals Inc | "composto, método de tratar um mamìfero que sofre de um doença ou de uma condição envolvendo as enzimas ciclooxiganase, composição farmacêutica, processo para e deuteração de um composto pelatroca de pelomenos um átomo de hidrogênio do dito composto com um átomo do deutério e processo para preparar m composto" |
| US20110053964A1 (en) * | 2006-08-22 | 2011-03-03 | Roger Tung | 4-aminoquinazoline derivatives and methods of use thereof |
| CA2661223A1 (en) * | 2006-08-22 | 2008-02-28 | Concert Pharmaceuticals Inc. | 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 |
| 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 |
| 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 |
| 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 |
| WO2008066620A2 (en) * | 2006-10-20 | 2008-06-05 | Concert Pharmaceuticals Inc. | Dibenzothiazepine derivatives |
| WO2008127300A2 (en) * | 2006-10-23 | 2008-10-23 | Concert Pharmaceuticals Inc. | Oxazolidinone derivatives and methods of use |
| US8796267B2 (en) | 2006-10-23 | 2014-08-05 | Concert Pharmaceuticals, Inc. | Oxazolidinone derivatives and methods of use |
| WO2008063600A2 (en) * | 2006-11-17 | 2008-05-29 | Concert Pharmaceuticals Inc. | Triazolyl tropane derivatives |
| WO2008076949A2 (en) * | 2006-12-15 | 2008-06-26 | Concert Pharmaceuticals Inc. | Quinazoline derivatives and methods of treatment |
| US20100260674A1 (en) * | 2006-12-15 | 2010-10-14 | Concert Pharmaceuticals, Inc. | Quinazoline derivatives and methods of treatment |
| US20090325976A1 (en) * | 2006-12-21 | 2009-12-31 | Concert Pharmaceuticals Inc. | Prostacyclin derivatives |
| WO2008088727A2 (en) * | 2007-01-12 | 2008-07-24 | Concert Pharmaceuticals, Inc. | Endothelin receptor antagonists |
| US8080549B2 (en) * | 2007-01-12 | 2011-12-20 | Concert Pharmaceuticals, Inc. | Endothelin receptor antagonists |
| EP2118073A2 (en) * | 2007-02-02 | 2009-11-18 | Concert Pharmaceuticals Inc. | Selective endothelin type-a antagonists |
| EP2125717B1 (en) * | 2007-02-26 | 2013-07-03 | Concert Pharmaceuticals Inc. | Deuterated derivatives of silodosin as alpha ia-adrenoreceptor antagonists |
| US20100076010A1 (en) * | 2007-02-26 | 2010-03-25 | Concert Pharmaceuticals, Inc. | Alpha 1a-adrenoceptor antagonists |
| ATE509015T1 (de) * | 2007-03-07 | 2011-05-15 | Concert Pharmaceuticals Inc | Deuterierte piperazinderivate als verbindungen gegen angina |
| CA2681628C (en) * | 2007-03-16 | 2016-10-18 | Concert Pharmaceuticals, Inc. | Inhibitors of cholesterol ester transfer protein |
| WO2008130863A2 (en) * | 2007-04-11 | 2008-10-30 | Auspex Pharmaceuticals, Inc. | Substituted benzimidazoles |
| WO2008127640A2 (en) * | 2007-04-11 | 2008-10-23 | Auspex Pharmaceuticals, Inc. | Substituted benzimidazoles |
| US8198305B2 (en) * | 2007-04-13 | 2012-06-12 | Concert Pharmaceuticals Inc. | 1,2-benzisoxazol-3-yl compounds |
| EP2152689B1 (en) | 2007-04-25 | 2013-01-02 | Concert Pharmaceuticals Inc. | Analogues of cilostazol |
| US8349817B2 (en) * | 2007-04-25 | 2013-01-08 | Concert Pharmaceuticals, Inc. | Analogues of cilostazol |
| CA3208128A1 (en) | 2007-05-01 | 2008-11-13 | Sun Pharmaceutical Industries, Inc. | Morphinan compounds |
| AU2008247805A1 (en) * | 2007-05-01 | 2008-11-13 | Concert Pharmaceuticals Inc. | Naphthyl(ethyl) acetamides |
| EP2345653B1 (en) * | 2007-05-01 | 2012-12-26 | Concert Pharmaceuticals Inc. | Morphinan compounds |
| 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 |
| ATE447554T1 (de) | 2007-06-12 | 2009-11-15 | Concert Pharmaceuticals Inc | Azapeptid-derivate als hiv-protease-inhibitoren |
| US20080312247A1 (en) * | 2007-06-13 | 2008-12-18 | 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 |
| WO2009023233A1 (en) | 2007-08-14 | 2009-02-19 | Concert Pharmaceuticals, Inc. | Substituted oxazolidinone derivatives |
| 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 |
| US20090062305A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched cetirizine |
| US20090062399A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched sertraline |
| US20090062374A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched lasofoxifene |
| US20090062393A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched pregabalin |
| US20090062283A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched linezolid |
| 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 |
| 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 |
| US20090076165A1 (en) * | 2007-09-12 | 2009-03-19 | Protia, Llc | Deuterium-enriched memantine |
| US8288414B2 (en) * | 2007-09-12 | 2012-10-16 | Deuteria Pharmaceuticals, Inc. | Deuterium-enriched lenalidomide |
| WO2009035662A1 (en) * | 2007-09-12 | 2009-03-19 | Concert Pharmaceuticals, Inc. | Deuterated 4 -oxoquinoline derivatives for the treatment of hiv infection |
| US20090076116A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched carvediolo |
| US7919516B2 (en) * | 2007-09-13 | 2011-04-05 | Protia, Llc | Deuterium-enriched ondansetron |
| JP5647519B2 (ja) | 2007-09-13 | 2014-12-24 | 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 | 重水素化カテコールおよびベンゾ［ｄ］［１，３］ジオキソールおよびその誘導体の合成 |
| US20090076161A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched bupropion |
| US20090075965A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched amoxicilin |
| US20090076118A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched saxagliptin |
| US20090076112A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched eltrombopag |
| US20090076010A1 (en) * | 2007-09-13 | 2009-03-19 | Protia, Llc | Deuterium-enriched lamotrigine |
| US20090076034A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched bms-690514 |
| 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 |
| US20090075991A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched efavirenz |
| US20090076148A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched pravastatin |
| US20090076102A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched muraglitazar |
| US20090076038A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched entecavir |
| 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 |
| US20090076018A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched ranolazine |
| US20090076138A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched darunavir |
| US20090076128A1 (en) * | 2007-09-15 | 2009-03-19 | Protia Llc | Deuterium-enriched topiramate |
| US20090076163A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched dapoxetine |
| US20090076000A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched mycophenolate mofetil |
| US20090076040A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched valganciclovir |
| US20090076157A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched senicapoc |
| 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 |
| US20090076017A1 (en) * | 2007-09-15 | 2009-03-19 | Protia, Llc | Deuterium-enriched trabectedin |
| 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 |
| US20090076167A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched tramiprosate |
| US20090118238A1 (en) * | 2007-09-17 | 2009-05-07 | Protia, Llc | Deuterium-enriched alendronate |
| US20090076126A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched enalapril |
| US20090076154A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched vorinostat |
| US20090076058A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched finasteride |
| US20090076144A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched bazedoxifene |
| US20090075997A1 (en) * | 2007-09-19 | 2009-03-19 | Protia, Llc | Deuterium-enriched satavaptan |
| 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 |
| US20090076127A1 (en) * | 2007-09-19 | 2009-03-19 | Protia, Llc | Deuterium-enriched larotaxel |
| 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 |
| US20090082462A1 (en) * | 2007-09-25 | 2009-03-26 | Protia, Llc | Deuterium-enriched armodafinil |
| US20090082459A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched guanfacine |
| US20090082387A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched nvp-bez234 |
| US20090082452A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched lumiracoxib |
| US8722710B2 (en) | 2007-09-26 | 2014-05-13 | Deuterx, Llc | Deuterium-enriched pioglitazone |
| 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 |
| US20090082471A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched fingolimod |
| US20090082364A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched levocedtirizine |
| US20090082363A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched posaconazole |
| US20090082335A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched oxcarbazepine |
| US20090143363A1 (en) * | 2007-10-15 | 2009-06-04 | 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 |
| US8592487B2 (en) * | 2007-10-26 | 2013-11-26 | Concert Pharmaceuticals, Inc. | Deuterated darunavir |
| CA2703591C (en) * | 2007-10-26 | 2013-05-07 | Concert Pharmaceuticals, Inc. | Deuterated darunavir |
| JP2011503231A (ja) * | 2007-11-20 | 2011-01-27 | 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 | Ｈｃｖ感染処置のためのペプチド |
| WO2009076373A1 (en) * | 2007-12-10 | 2009-06-18 | Concert Pharmaceuticals Inc. | Heterocyclic kinase inhibitors |
| WO2009079637A1 (en) * | 2007-12-18 | 2009-06-25 | Concert Pharmaceuticals, Inc. | Tetrahydroisoquinoline derivatives |
| US8609673B2 (en) * | 2008-01-22 | 2013-12-17 | Concert Pharmaceuticals, Inc. | Vandetanib derivatives |
| US7855204B2 (en) * | 2008-01-22 | 2010-12-21 | Concert Pharmaceuticals Inc. | Derivatives of gefitinib |
| 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 |
| US20090209550A1 (en) * | 2008-02-20 | 2009-08-20 | Auspex Pharmaceuticals, Inc. | Substituted triazolopyridines |
| KR20100121527A (ko) * | 2008-02-29 | 2010-11-17 | 콘서트 파마슈티컬즈, 인크. | 치환된 잔틴 유도체 |
| WO2009114809A1 (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 |
| CN102083801A (zh) * | 2008-03-28 | 2011-06-01 | 康瑟特制药公司 | 喹唑啉衍生物和治疗方法 |
| CN102089262A (zh) * | 2008-04-09 | 2011-06-08 | 康瑟特制药公司 | 3-(2-羟基-5-甲基苯基)-n，n-二异丙基-3-苯丙胺的衍生物及其使用方法 |
| 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 |
| US8367674B2 (en) * | 2008-04-17 | 2013-02-05 | 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 |
| TWI523652B (zh) | 2008-07-15 | 2016-03-01 | 泰瑞克公司 | 氘化苄基苯衍生物及使用方法 |
| WO2010011868A2 (en) * | 2008-07-23 | 2010-01-28 | Auspex Pharmaceuticals | Pyridine sulfonamide modulators of endothelin-a-receptor |
| WO2010019557A1 (en) * | 2008-08-12 | 2010-02-18 | Concert Pharmaceuticals Inc. | N-phenyl-2-pyrimidineamine derivatives |
| AU2009285533B2 (en) | 2008-08-29 | 2014-02-13 | Concert Pharmaceuticals Inc. | Substituted triazolo-pyridazine derivatives |
| JP5586606B2 (ja) * | 2008-09-02 | 2014-09-10 | アクチミス ファーマシューティカルズ インコーポレーテッド | Ｃｒｔｈ２アンタゴニストとしての同位体富化されたピリミジン−５−イル酢酸誘導体 |
| BRPI0913518A2 (pt) * | 2008-09-03 | 2016-07-26 | Teva Pharma | composto, composição farmacêutica, e, método de tratamento de um distúrbio mediado por função imune |
| 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 |
| EA030882B1 (ru) | 2008-09-19 | 2018-10-31 | Консерт Фармасьютикалз Инк. | Дейтерированные морфинановые соединения и их применение |
| US20100087455A1 (en) * | 2008-10-06 | 2010-04-08 | Auspex Pharmaceuticals, Inc. | Substituted xanthine compounds |
| AU2009305563C1 (en) | 2008-10-17 | 2015-09-03 | Signature Therapeutics, Inc. | Pharmaceutical compositions with attenuated release of phenolic opioids |
| 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 |
| US20100143354A1 (en) * | 2008-12-04 | 2010-06-10 | Auspex Pharmaceuticals, Inc. | Triazine dna modifiers |
| WO2010065755A1 (en) * | 2008-12-04 | 2010-06-10 | Concert Pharmaceuticals, Inc. | Deuterated pyridinones |
| US20100144657A1 (en) * | 2008-12-09 | 2010-06-10 | Auspex Pharmaceuticals, Inc. | PHENYLPIPERIDINE MODULATORS OF mu-OPIOID RECEPTORS |
| US20100159034A1 (en) * | 2008-12-15 | 2010-06-24 | Auspex Pharmaceuticals, Inc. | Pyrrolidinone inhibitors of pde-4 |
| KR101682427B1 (ko) * | 2008-12-23 | 2016-12-05 | 아쿠일루스 파마슈티컬즈, 인코포레이티드 | 통증 및 기타 질병을 치료하기 위한 화합물 및 방법 |
| WO2010093434A1 (en) * | 2009-02-11 | 2010-08-19 | 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 |
| WO2010107791A2 (en) | 2009-03-17 | 2010-09-23 | Concert Pharmaceuticals, Inc. | 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 |
| KR20120013403A (ko) | 2009-04-22 | 2012-02-14 | 액시킨 파마수티컬스 인코포레이티드 | 2,5-이치환된 아릴설폰아마이드 ｃｃｒ3 길항제 |
| SI2421808T1 (sl) | 2009-04-23 | 2013-12-31 | Concert Pharmaceuticals Inc. | Analogi 4-hidroksi maslene kisline |
| WO2010127272A2 (en) * | 2009-04-30 | 2010-11-04 | Concert Pharmaceuticals, Inc. | Hydroxyethylamino sulfonamide derivatives |
| US9468637B2 (en) | 2009-05-13 | 2016-10-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US8410082B2 (en) | 2009-05-22 | 2013-04-02 | Concert Pharmaceuticals, Inc. | Fluorinated diaryl urea derivatives |
| WO2010144499A2 (en) * | 2009-06-09 | 2010-12-16 | Medolution Limited | Urea derivatives as kinase inhibitors |
| AU2010260249B2 (en) | 2009-06-18 | 2013-09-05 | 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 |
| EP2454265A2 (en) * | 2009-07-17 | 2012-05-23 | Rigel Pharmaceuticals, Inc. | Deuterated 2, 4-pyrimidinediamine compounds and prodrugs thereof and their uses |
| US20110082147A1 (en) * | 2009-07-24 | 2011-04-07 | 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 |
| US9260432B2 (en) | 2009-09-02 | 2016-02-16 | Concert Pharmaceuticals, Inc. | Substituted derivatives of bicyclic [4.3.0] heteroaryl compounds |
| IN2012DN01642A (enExample) * | 2009-09-02 | 2015-06-05 | Concert Pharmaceuticals Inc | |
| JP2013503862A (ja) | 2009-09-08 | 2013-02-04 | シグネーチャー セラピューティクス，インク． | 酵素切断可能なケトン修飾オピオイドプロドラッグとその任意選択のインヒビターとを含んでなる組成物 |
| US20120315244A1 (en) | 2009-09-30 | 2012-12-13 | President And Fellows Of Harvard College | Methods for Modulation of Autophagy Through the Modulation of Autophagy-Inhibiting Gene Products |
| US8278460B2 (en) * | 2009-10-15 | 2012-10-02 | Concert Pharmaceuticals, Inc. | Substituted benzimidazoles |
| CA2778907A1 (en) * | 2009-10-28 | 2011-05-12 | Anadys Pharmaceuticals, Inc. | Deuterated 5,6-dihydro-1h-pyridin-2-one compounds |
| 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 |
| WO2011061243A1 (en) * | 2009-11-21 | 2011-05-26 | 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 |
| CA2790199A1 (en) * | 2010-02-24 | 2011-09-01 | Auspex Pharmaceuticals, Inc. | Trimethoxyphenyl inhibitors of tyrosine kinase |
| AU2011223895A1 (en) * | 2010-03-01 | 2012-09-13 | Concert Pharmaceuticals Inc. | Fluorouracil derivatives |
| WO2011109464A1 (en) * | 2010-03-02 | 2011-09-09 | Concert Pharmaceuticals Inc. | Deuterated tetrahydronaphthalene derivatives |
| US8575361B2 (en) | 2010-03-02 | 2013-11-05 | Concert Pharmaceuticals Inc. | Tetrahydronaphthalene derivatives |
| WO2011116066A1 (en) | 2010-03-17 | 2011-09-22 | Concert Pharmaceuticals, Inc. | Derivatives of dimethylcurcumin |
| WO2011133150A1 (en) * | 2010-04-21 | 2011-10-27 | Pharmacofore, Inc. | Compositions comprising enzyme-cleavable prodrugs of active agents and inhibitors thereof |
| AU2010351605C1 (en) * | 2010-04-21 | 2015-08-06 | Signature Therapeutics, Inc. | Compositions comprising enzyme-cleavable opioid prodrugs and inhibitors thereof |
| US20110262355A1 (en) | 2010-04-21 | 2011-10-27 | Jenkins Thomas E | Compositions comprising enzyme-cleavable opioid prodrugs and inhibitors thereof |
| WO2011133178A1 (en) | 2010-04-21 | 2011-10-27 | Pharmacofore, Inc | Compositions comprising enzyme-cleavable phenol-modified tapentadol prodrug |
| WO2011133348A1 (en) | 2010-04-21 | 2011-10-27 | Pharmacofore, Inc. | Compositions comprising enzyme-cleavable amphetamine prodrugs and inhibitors thereof |
| WO2012009446A1 (en) | 2010-07-16 | 2012-01-19 | Concert Pharmaceuticals Inc. | Novel pyrimidinecarboxamide derivatives |
| 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 |
| WO2012031072A1 (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 |
| NZ608120A (en) * | 2010-09-03 | 2014-12-24 | Ivax Int Gmbh | Deuterated analogs of pridopidine useful as dopaminergic stabilizers |
| CN103384472B (zh) | 2011-01-11 | 2016-01-20 | 特色疗法股份有限公司 | 包含酶可裂解的羟考酮药物前体的组合物 |
| WO2012096886A1 (en) | 2011-01-11 | 2012-07-19 | Signature Therapeutics, Inc. | Compositions comprising enzyme-cleavable oxycodone prodrug |
| WO2012099915A1 (en) * | 2011-01-19 | 2012-07-26 | Hongwen Zhu | Thiazolidine derivatives and their therapeutic use |
| MX355742B (es) | 2011-02-14 | 2018-04-26 | Concert Pharmaceuticals Inc | Análogos deuterados del ácido 4-hidroxibutírico. |
| US9145390B2 (en) | 2011-03-03 | 2015-09-29 | Concert Pharmaceuticals, Inc. | Derivatives of pyrazole-substituted amino-heteroaryl compounds |
| WO2012122028A2 (en) | 2011-03-04 | 2012-09-13 | Concert Pharmaceuticals Inc. | Pyrazinoisoquinoline compounds |
| BR112013022946A2 (pt) | 2011-03-09 | 2017-07-18 | Signature Therapeutics Inc | pró-fármacos de agentes ativos com ligantes heterocíclocos |
| WO2012122420A2 (en) | 2011-03-09 | 2012-09-13 | Pharmacofore, Inc. | Opioid prodrugs with heterocyclic linkers |
| CA2867134C (en) | 2011-03-28 | 2019-05-07 | Sheila Dewitt | 2',6'-dioxo-3'-deutero-piperdin-3-yl-isoindoline compounds |
| WO2012151361A1 (en) * | 2011-05-03 | 2012-11-08 | Concert Pharmaceuticals Inc. | Carbamoylpyridone derivatives |
| MX362218B (es) * | 2011-05-04 | 2019-01-09 | Balance Therapeutics Inc | Derivados de pentilentetrazol. |
| HUE047354T2 (hu) | 2011-05-18 | 2020-04-28 | Vertex Pharmaceuticals Europe Ltd | Ivacaftor deuterizált származékai |
| CN104114544A (zh) * | 2012-02-08 | 2014-10-22 | 默克专利有限公司 | 用作卵泡刺激素受体激动剂的氘化噻唑烷酮类似物 |
| MX2014012384A (es) | 2012-04-13 | 2014-11-26 | Concert Pharmaceuticals Inc | Derivados sustituidos de xantina. |
| US9249093B2 (en) | 2012-04-20 | 2016-02-02 | Concert Pharmaceuticals, Inc. | Deuterated rigosertib |
| EP3450434B1 (en) * | 2012-06-15 | 2021-02-24 | CoNCERT Pharmaceuticals, Inc. | Deuterated derivatives of ruxolitinib |
| US9181190B2 (en) | 2012-07-04 | 2015-11-10 | Concert Pharmaceuticals, Inc. | Deuterated vercirnon |
| CA2908929C (en) | 2012-07-12 | 2021-01-26 | Concert Pharmaceuticals, Inc. | Deuterated idebenone |
| CN104507946A (zh) | 2012-07-30 | 2015-04-08 | 康塞特医药品有限公司 | 氘代依鲁替尼 |
| EP2885303B1 (en) | 2012-08-17 | 2018-12-26 | CoNCERT Pharmaceuticals, Inc. | Deuterated baricitinib |
| US20150210624A1 (en) * | 2012-08-22 | 2015-07-30 | Concert Pharmaceuticals, Inc. | Deuterated 4-hydroxybutyric acid analogs |
| JP2015531776A (ja) * | 2012-09-04 | 2015-11-05 | セルジーン コーポレイション | ３−（５−アミノ−２−メチル−４−オキソキナゾリン−３（４ｈ）−イル）ピペリジン−２，６−ジオンのアイソトポログ及びその製造方法 |
| CA2881129A1 (en) * | 2012-09-07 | 2014-03-13 | Axikin Pharmaceuticals, Inc. | Isotopically enriched arylsulfonamide ccr3 antagonists |
| JP2015534989A (ja) | 2012-10-22 | 2015-12-07 | 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 | ｛ｓ−３−（４−アミノ−１−オキソ−イソインドリン−２−イル）（ピペリジン−３，４，４，５，５−ｄ５）−２，６−ジオン｝の固体形態 |
| US9518027B2 (en) | 2013-01-09 | 2016-12-13 | Concert Pharmaceuticals, Inc. | Deuterated momelotinib |
| JP6359563B2 (ja) | 2013-01-14 | 2018-07-18 | デュートルクス・リミテッド・ライアビリティ・カンパニーＤｅｕｔｅＲｘ， ＬＬＣ | ３−（５置換−４−オキソキナゾリン−３（４ｈ）−イル）−３−ジュウテロピペリジン−２，６−ジオン誘導体 |
| 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 |
| WO2014127331A1 (en) | 2013-02-17 | 2014-08-21 | Intra-Cellular Therapies, Inc. | Novel uses |
| US8969581B2 (en) | 2013-03-14 | 2015-03-03 | Deuterx, Llc | 5-deutero-2,4-thiazolidinedione derivatives and compositions comprising and methods of using the same |
| 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 |
| AU2014237569B2 (en) | 2013-03-15 | 2019-03-14 | 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 |
| WO2015031741A1 (en) | 2013-08-30 | 2015-03-05 | Concert Pharmaceuticals, Inc. | Deuterated derivatives of a thienotriazolodiazapine bromodomain-containing protein inhibitor |
| KR102373288B1 (ko) | 2013-12-03 | 2022-03-10 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 신규한 방법 |
| DK3077397T3 (da) * | 2013-12-06 | 2019-12-16 | Vertex Pharma | 2-amino-6-fluor-n-[5-fluor-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamidforbindelse anvendelig som atr-kinase-inhibitor, dens fremstilling, forskellige faste former og radiomarkerede derivater deraf |
| 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 |
| CA2936823A1 (en) * | 2014-01-27 | 2015-07-30 | Auspex Pharmaceuticals, Inc. | Benzoquinoline inhibitors of vesicular monoamine transporter 2 |
| EP3102190A4 (en) | 2014-02-07 | 2017-09-06 | Auspex Pharmaceuticals, Inc. | Novel pharmaceutical formulations |
| JP6526060B2 (ja) | 2014-02-10 | 2019-06-05 | 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 | 置換トリアゾロベンゾジアゼピン |
| BR112016023162B1 (pt) | 2014-04-04 | 2022-11-29 | Intra-Cellular Therapies, Inc | Compostos orgânicos gama-carbolinas, composições farmacêuticas compreendendo os ditos compostos e uso dos mesmos no tratamento ou na profilaxia de transtornos de sistema nervoso central |
| ES2732442T3 (es) * | 2014-06-20 | 2019-11-22 | Intra Cellular Therapies Inc | Compuestos orgánicos |
| JP6591530B2 (ja) | 2014-08-07 | 2019-10-16 | 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 |
| CA2959965A1 (en) * | 2014-09-02 | 2016-03-10 | Bhupinder Singh | Pharmaceutical formulations comprising tetrahydrocurcumin and lipids |
| WO2016069630A1 (en) | 2014-10-27 | 2016-05-06 | Concert Pharmaceuticals, Inc. | Pyrimidine phosphonic acid esters bearing at least one deuterium atom |
| US20190055235A1 (en) * | 2014-12-17 | 2019-02-21 | Zenith Epigenetics Ltd. | Substituted bicyclic compounds as bromodomain inhibitors |
| EP3250557B1 (en) | 2015-01-29 | 2024-11-20 | Signal Pharmaceuticals, LLC | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
| HK1249893A1 (zh) | 2015-03-31 | 2018-11-16 | Vertex Pharmaceuticals (Europe) Limited | 氘代vx-661 |
| PL3277681T3 (pl) * | 2015-04-02 | 2019-10-31 | Merck Patent Gmbh | Imidazolonylochinoliny i ich zastosowanie jako inhibitorów kinazy atm |
| WO2016176335A1 (en) * | 2015-04-27 | 2016-11-03 | 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 |
| JP6595011B2 (ja) * | 2015-06-26 | 2019-10-23 | 重▲慶▼迪康▲爾▼▲楽▼制▲薬▼有限公司 | 新規ホスホジエステラーゼ５阻害剤とその使用 |
| 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 |
| HK1258473A1 (zh) | 2015-09-25 | 2019-11-15 | Vertex Pharmaceuticals (Europe) Limited | 氘代cftr增效剂 |
| WO2017069878A1 (en) * | 2015-10-21 | 2017-04-27 | NeuForm Pharmaceuticals, Inc. | Deuterated compounds for treating hematologic malignancies, and compositions and methods thereof |
| 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 |
| US11267777B2 (en) | 2015-11-19 | 2022-03-08 | Concert Pharmaceuticals, Inc. | Deuterated EPI-743 |
| IL296884B2 (en) | 2016-01-26 | 2024-05-01 | Intra Cellular Therapies Inc | Condensed heterocyclic converted gamma carbonyls for use in the treatment of central nervous system disorders |
| US10519193B2 (en) * | 2016-02-02 | 2019-12-31 | Shenzhen Targetrx, Inc. | Steroidal compound, composition containing the same and use thereof |
| EP3416629A4 (en) | 2016-02-16 | 2019-08-07 | CoNCERT Pharmaceuticals, Inc. | DEUTERATED GFT-505 |
| PL3407889T3 (pl) | 2016-03-25 | 2021-11-22 | Intra-Cellular Therapies, Inc. | Związki organiczne i ich zastosowanie w leczeniu lub zapobieganiu zaburzeniom ośrodkowego układu nerwowego |
| 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 |
| WO2018126140A1 (en) | 2016-12-29 | 2018-07-05 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2018126143A1 (en) | 2016-12-29 | 2018-07-05 | Intra-Cellular Therapies, Inc. | Organic compounds |
| CN116327770B (zh) | 2017-03-24 | 2025-10-31 | 细胞内治疗公司 | 新组合物和方法 |
| CN110740993B (zh) * | 2017-05-16 | 2023-09-01 | 沃泰克斯药物股份有限公司 | 用作钠通道调节剂的氘代吡啶酮酰胺及其前药 |
| 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 |
| IL274585B1 (en) | 2017-11-22 | 2025-09-01 | Concert Pharmaceuticals Inc | Deuterated D-serine Analogs and Their Uses |
| WO2019109021A1 (en) | 2017-12-01 | 2019-06-06 | Vertex Pharmaceuticals Incorporated | Processes for making modulators of cystic fibrosis transmembrane conductance regulator |
| WO2019120194A1 (zh) * | 2017-12-22 | 2019-06-27 | 深圳市塔吉瑞生物医药有限公司 | 一种取代的吡唑并[1,5-a]嘧啶化合物及其药物组合物及用途 |
| US11345703B2 (en) | 2018-01-23 | 2022-05-31 | Shenzhen Targetrx, Inc. | Substituted pyrazolo[1,5-a]pyrimidine macrocyclic compound |
| EP3746081A4 (en) | 2018-01-31 | 2021-10-27 | Intra-Cellular Therapies, Inc. | Novel uses |
| CA3094949A1 (en) | 2018-03-23 | 2019-09-26 | Intra-Cellular Therapies, Inc. | Deuterated heterocycle fused gamma-carbolines |
| EP3782998B1 (en) * | 2018-04-16 | 2023-05-10 | Shenzhen TargetRx, Inc. | Substituted pyrrolotriazine compound, pharmaceutical composition thereof and use thereof |
| US11684622B2 (en) * | 2018-06-19 | 2023-06-27 | Celecor Therapeutics, Inc. | Deuterated RUC-4 |
| WO2020011141A1 (zh) * | 2018-07-12 | 2020-01-16 | 深圳市塔吉瑞生物医药有限公司 | 一种二芳基吡唑化合物及包含该化合物的组合物及其用途 |
| US12144808B2 (en) | 2018-08-29 | 2024-11-19 | Intra-Cellular Therapies, Inc. | Compositions and methods |
| MX2021002322A (es) | 2018-08-31 | 2021-04-28 | Intra Cellular Therapies Inc | Nuevos metodos. |
| AU2019331490B2 (en) | 2018-08-31 | 2025-04-24 | Intra-Cellular Therapies, Inc. | Novel 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 |
| KR20210066833A (ko) * | 2018-09-26 | 2021-06-07 | 지앙수 헨그루이 메디슨 컴퍼니 리미티드 | 엑사테칸 유사체의 리간드-약물 접합체, 이를 위한 제조 방법, 및 이의 적용 |
| 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 |
| US20220227772A1 (en) * | 2019-05-07 | 2022-07-21 | The Trustees Of The University Of Pennsylvania | Deuterated triazolopyrimidines |
| CA3141223A1 (en) | 2019-07-07 | 2021-01-14 | Sharon Mates | Novel methods |
| 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 |
| US12410175B2 (en) * | 2019-09-03 | 2025-09-09 | Intra-Cellular Therapies, Inc. | 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 |
| EP4433466A2 (en) | 2021-11-17 | 2024-09-25 | Terran Biosciences Inc. | Phenethylamine compounds salts, polymorphic forms and methods of use thereof |
| AU2022414887A1 (en) * | 2021-12-14 | 2024-07-25 | Xizang Haisco Pharmaceutical Co., Ltd. | Tricyclic fused heterocyclic pde3/4 dual inhibitor and use thereof |
| JP2025503998A (ja) * | 2022-01-27 | 2025-02-06 | ピーエムブイ ファーマシューティカルズ， インコーポレイテッド | 変異体ｐ５３機能を回復するための重水素化化合物 |
| 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 |
| US5433959A (en) | 1986-02-13 | 1995-07-18 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| US6749864B2 (en) | 1986-02-13 | 2004-06-15 | 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 |
| EP0382489B1 (en) | 1989-02-10 | 1994-11-17 | Takeda Chemical Industries, Ltd. | Use of benzimidazole derivatives as antibacterial agents |
| 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 |
| US6221335B1 (en) * | 1994-03-25 | 2001-04-24 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| AU707748B2 (en) * | 1994-03-25 | 1999-07-22 | Isotechnika Inc. | Enhancement of the efficacy of drugs by deuteration |
| US6645988B2 (en) | 1996-01-04 | 2003-11-11 | Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of 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 |
| US5840737A (en) | 1996-01-04 | 1998-11-24 | The Curators Of The University Of Missouri | Omeprazole solution and method for 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 |
| KR100554924B1 (ko) | 1998-05-18 | 2006-03-03 | 다케다 야쿠힌 고교 가부시키가이샤 | 구강내 붕괴 정제 |
| CA2581111A1 (en) | 1998-07-28 | 2000-02-10 | Takeda Pharmaceutical Company Limited | Rapidly disintegrable solid preparation |
| 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 |
| TWI275587B (en) | 1999-06-17 | 2007-03-11 | Takeda Chemical Industries Ltd | A crystal of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole |
| DE60001623T2 (de) * | 1999-12-03 | 2003-12-18 | Pfizer Products Inc., Groton | Sulfamoylheteroarylpyrazolverbindungen zur Verwendung als analgetisches/entzündungshemmendes Mittel |
| 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 |
| EP1310252A4 (en) | 2000-08-18 | 2009-06-10 | Takeda Pharmaceutical | INJECTIONS |
| MY137726A (en) | 2000-11-22 | 2009-03-31 | Nycomed Gmbh | Freeze-dried pantoprazole preparation and pantoprazole injection |
| EP1337525B8 (en) | 2000-12-01 | 2011-10-05 | Takeda Pharmaceutical Company Limited | Process for the crystallization of (r)- or (s)-lansoprazole |
| 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 |
| WO2007012651A1 (en) | 2005-07-26 | 2007-02-01 | Nycomed Gmbh | Isotopically substituted pantoprazole |
| EA016814B1 (ru) * | 2005-07-26 | 2012-07-30 | Никомед Гмбх | Замещенные изотопами ингибиторы протонного насоса |
| US20080033011A1 (en) | 2005-07-29 | 2008-02-07 | Concert Pharmaceuticals Inc. | Novel benzo[d][1,3]-dioxol derivatives |
| CA2619518A1 (en) | 2005-08-22 | 2007-03-01 | Nycomed Gmbh | Isotopically substituted benzimidazole derivatives |
| 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 |
| JP2009539866A (ja) | 2006-06-05 | 2009-11-19 | オースペックス・ファーマシューティカルズ・インコーポレイテッド | 置換エリスロマイシンアナログの調製および有用性 |
| KR101109866B1 (ko) | 2006-09-21 | 2012-04-12 | 라퀄리아 파마 인코포레이티드 | 선택성 산 펌프 억제제로서의 벤즈이미다졸 유도체 |
| WO2008114123A1 (en) | 2007-03-21 | 2008-09-25 | Raqualia Pharma Inc. | Spiro benzimidazole derivatives as acid pump inhibitors |
| WO2008130863A2 (en) | 2007-04-11 | 2008-10-30 | Auspex Pharmaceuticals, Inc. | Substituted benzimidazoles |
| WO2008127640A2 (en) | 2007-04-11 | 2008-10-23 | 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 |
-
2006
- 2006-10-04 CA CA002624179A patent/CA2624179A1/en not_active Abandoned
- 2006-10-04 WO PCT/US2006/038819 patent/WO2007041630A1/en not_active Ceased
- 2006-10-04 BR BRPI0617987-8A patent/BRPI0617987A2/pt not_active IP Right Cessation
- 2006-10-04 CN CN2006800426099A patent/CN101309917B/zh active Active
- 2006-10-04 US US11/544,407 patent/US7598273B2/en active Active
- 2006-10-04 EP EP06816227A patent/EP1934201A1/en not_active Withdrawn
- 2006-10-04 JP JP2008534658A patent/JP2009511481A/ja active Pending
- 2006-10-04 AU AU2006299424A patent/AU2006299424A1/en not_active Abandoned
-
2008
- 2008-03-20 IL IL190331A patent/IL190331A0/en unknown
-
2009
- 2009-03-27 US US12/413,323 patent/US20090209592A1/en not_active Abandoned
- 2009-03-27 US US12/413,365 patent/US20090215831A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN101309917B (zh) | 2013-09-11 |
| US20090209592A1 (en) | 2009-08-20 |
| JP2009511481A (ja) | 2009-03-19 |
| CN101309917A (zh) | 2008-11-19 |
| EP1934201A1 (en) | 2008-06-25 |
| WO2007041630A1 (en) | 2007-04-12 |
| US7598273B2 (en) | 2009-10-06 |
| HK1124336A1 (en) | 2009-07-10 |
| IL190331A0 (en) | 2009-09-22 |
| BRPI0617987A2 (pt) | 2011-08-16 |
| US20070082929A1 (en) | 2007-04-12 |
| US20090215831A1 (en) | 2009-08-27 |
| AU2006299424A1 (en) | 2007-04-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20140717 |