NO312672B1 - Tri-substituerte fenylderivater anvendelige som PDE IV- inhibitorer, fremgangsmåte for fremstilling derav og farmasöytiskepreparater inneholdende dem - Google Patents
Tri-substituerte fenylderivater anvendelige som PDE IV- inhibitorer, fremgangsmåte for fremstilling derav og farmasöytiskepreparater inneholdende dem Download PDFInfo
- Publication number
- NO312672B1 NO312672B1 NO19965524A NO965524A NO312672B1 NO 312672 B1 NO312672 B1 NO 312672B1 NO 19965524 A NO19965524 A NO 19965524A NO 965524 A NO965524 A NO 965524A NO 312672 B1 NO312672 B1 NO 312672B1
- Authority
- NO
- Norway
- Prior art keywords
- pyridine
- group
- cyclopentyloxy
- methoxyphenyl
- ethyl
- Prior art date
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- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title claims abstract description 8
- -1 Tri-substituted phenyl Chemical class 0.000 title abstract description 25
- 238000000034 method Methods 0.000 title abstract description 15
- 238000002360 preparation method Methods 0.000 title abstract description 15
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- 239000008194 pharmaceutical composition Substances 0.000 title 1
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 73
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 35
- 239000000203 mixture Substances 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 19
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- 125000005843 halogen group Chemical group 0.000 claims description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
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- 150000002739 metals Chemical class 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
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- HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 0.000 description 1
- QJKPGROOFFPTMM-YNMZEGNTSA-N n-[4-[4-[(1s)-1-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyridin-4-ylethoxy]phenyl]phenyl]methanesulfonamide;hydrochloride Chemical compound Cl.COC1=CC=C([C@H](CC=2C=CN=CC=2)OC=2C=CC(=CC=2)C=2C=CC(NS(C)(=O)=O)=CC=2)C=C1OC1CCCC1 QJKPGROOFFPTMM-YNMZEGNTSA-N 0.000 description 1
- NUIVIVXBBBZCFA-UHFFFAOYSA-N n-[4-[4-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyridin-4-ylethoxy]phenyl]phenyl]methanesulfonamide Chemical compound COC1=CC=C(C(CC=2C=CN=CC=2)OC=2C=CC(=CC=2)C=2C=CC(NS(C)(=O)=O)=CC=2)C=C1OC1CCCC1 NUIVIVXBBBZCFA-UHFFFAOYSA-N 0.000 description 1
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- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
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- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
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- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- GZKMGAXTHYGXEO-UHFFFAOYSA-M ruthenium(1+);triphenylphosphane;chloride Chemical compound [Ru]Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 GZKMGAXTHYGXEO-UHFFFAOYSA-M 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229940023144 sodium glycolate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- 238000005809 transesterification reaction Methods 0.000 description 1
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- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Lock And Its Accessories (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9412385A GB9412385D0 (en) | 1994-06-21 | 1994-06-21 | Chemical compounds |
| GB9412492A GB9412492D0 (en) | 1994-06-22 | 1994-06-22 | Chemical compounds |
| PCT/GB1995/001459 WO1995035281A1 (en) | 1994-06-21 | 1995-06-21 | Tri-substituted phenyl derivates useful as pde iv inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO965524D0 NO965524D0 (no) | 1996-12-20 |
| NO965524L NO965524L (no) | 1996-12-20 |
| NO312672B1 true NO312672B1 (no) | 2002-06-17 |
Family
ID=26305090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19965524A NO312672B1 (no) | 1994-06-21 | 1996-12-20 | Tri-substituerte fenylderivater anvendelige som PDE IV- inhibitorer, fremgangsmåte for fremstilling derav og farmasöytiskepreparater inneholdende dem |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US5786354A (cs) |
| EP (1) | EP0770065B1 (cs) |
| JP (1) | JP3856465B2 (cs) |
| CN (1) | CN1304372C (cs) |
| AT (1) | ATE263153T1 (cs) |
| AU (1) | AU707472B2 (cs) |
| CZ (1) | CZ293311B6 (cs) |
| DE (1) | DE69532808T2 (cs) |
| DK (1) | DK0770065T3 (cs) |
| ES (1) | ES2218548T3 (cs) |
| FI (1) | FI115302B (cs) |
| HU (1) | HUT76803A (cs) |
| NO (1) | NO312672B1 (cs) |
| NZ (1) | NZ288294A (cs) |
| PT (1) | PT770065E (cs) |
| RU (1) | RU2201921C2 (cs) |
| SK (1) | SK282661B6 (cs) |
| WO (1) | WO1995035281A1 (cs) |
Families Citing this family (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9222253D0 (en) * | 1992-10-23 | 1992-12-09 | Celltech Ltd | Chemical compounds |
| GB9304920D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| WO1995017399A1 (en) * | 1993-12-22 | 1995-06-29 | Celltech Therapeutics Limited | Trisubstituted phenyl derivatives, processes for their preparation and their use as phosphodiesterase (type iv) inhibitors |
| US6245774B1 (en) | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
| US5786354A (en) * | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
| GB9412571D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412573D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| US5710170A (en) * | 1995-12-15 | 1998-01-20 | Merck Frosst Canada, Inc. | Tri-aryl ethane derivatives as PDE IV inhibitors |
| CA2238875C (en) * | 1995-12-15 | 2003-09-16 | Merck Frosst Canada Inc. | Tri-aryl ethane derivatives as pde iv inhibitors |
| GB9526246D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526245D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526243D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| DE19605766A1 (de) * | 1996-02-16 | 1997-08-21 | Basf Ag | Substituierte 2-Phenylpyridine |
| GB9608435D0 (en) * | 1996-04-24 | 1996-06-26 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9619284D0 (en) * | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9622363D0 (en) | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9625184D0 (en) * | 1996-12-04 | 1997-01-22 | Celltech Therapeutics Ltd | Chemical compounds |
| EP0946523A1 (en) | 1996-12-23 | 1999-10-06 | Celltech Therapeutics Limited | Fused polycyclic 2-aminopyrimidine derivatives, their preparation and their use as protein tyrosine kinase inhibitors |
| GB9705361D0 (en) | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9713087D0 (en) * | 1997-06-20 | 1997-08-27 | Celltech Therapeutics Ltd | Chemical compounds |
| US6180650B1 (en) * | 1999-04-23 | 2001-01-30 | Merck Frosst Canada & Co. | Heterosubstituted pyridine derivatives as PDE 4 inhibitors |
| GB9914258D0 (en) * | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| CA2381802C (en) | 1999-08-21 | 2010-12-07 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Synergistic combination of roflumilast and salmeterol |
| HK1049787B (en) | 1999-10-01 | 2014-07-25 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| GB9924862D0 (en) | 1999-10-20 | 1999-12-22 | Celltech Therapeutics Ltd | Chemical compounds |
| US6410563B1 (en) | 1999-12-22 | 2002-06-25 | Merck Frosst Canada & Co. | Substituted 8-arylquinoline phosphodiesterase-4 inhibitors |
| MY123585A (en) | 2000-03-23 | 2006-05-31 | Merck Canada Inc | Tri-aryl-substituted-ethane pde4 inhibitors. |
| US6639077B2 (en) | 2000-03-23 | 2003-10-28 | Merck Frosst Canada & Co. | Tri-aryl-substituted-ethane PDE4 inhibitors |
| WO2001090076A1 (en) | 2000-05-25 | 2001-11-29 | Merck Frosst Canada & Co. | Fluoroalkoxy-substituted benzamide dichloropyridinyl n-oxide pde4 inhibitor |
| US6740666B2 (en) | 2000-12-20 | 2004-05-25 | Merck & Co., Inc. | Substituted 8-arylquinoline phosphodiesterase-4 inhibitors |
| US6699890B2 (en) | 2000-12-22 | 2004-03-02 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| DE10064997A1 (de) | 2000-12-23 | 2002-06-27 | Merck Patent Gmbh | Benzoylpyridazine |
| US7153871B2 (en) * | 2001-01-22 | 2006-12-26 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs |
| US7205320B2 (en) * | 2001-01-22 | 2007-04-17 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| CA2447765C (en) | 2001-05-24 | 2011-01-25 | Merck Frosst Canada & Co./Merck Frosst Canada & Cie | 1-biaryl-1,8-napthyridin-4-one phosphodiesterase-4 inhibitors |
| HRP20031081A2 (en) * | 2001-05-29 | 2005-10-31 | Schering Aktiengesellschaft | Cdk inhibiting pyrimidines, production thereof and their use as medicaments |
| JO2311B1 (en) | 2001-08-29 | 2005-09-12 | ميرك فروست كندا ليمتد | Alkyl inhibitors Ariel phosphodiesterase-4 |
| DE10150517A1 (de) * | 2001-10-12 | 2003-04-17 | Merck Patent Gmbh | Verwendung von Phosphodiesterase IV-Inhibitoren |
| CN101423497A (zh) | 2002-07-19 | 2009-05-06 | 记忆药物公司 | 作为磷酸二酯酶4抑制剂的6-氨基-1h-吲唑和4-氨基苯并呋喃化合物 |
| CN1688545A (zh) | 2002-07-19 | 2005-10-26 | 记忆药物公司 | 磷酸二酯酶4抑制剂,包括n－取代的苯胺及二苯胺类似物 |
| US7087625B2 (en) * | 2002-11-19 | 2006-08-08 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| AU2004226353A1 (en) | 2003-04-01 | 2004-10-14 | Laboratoires Serono Sa | Inhibitors of phosphodiesterases in infertility |
| DE10344742A1 (de) | 2003-09-25 | 2005-04-14 | Endress + Hauser Flowtec Ag, Reinach | Verfahren zum Einstellen einer mechanischen Resonanzfrequenz |
| MY141255A (en) * | 2003-12-11 | 2010-03-31 | Memory Pharm Corp | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs |
| WO2006044457A1 (en) * | 2004-10-13 | 2006-04-27 | Wyeth | N-benzenesulfonyl substituted anilino-pyrimidine analogs |
| EP2275096A3 (en) | 2005-08-26 | 2011-07-13 | Braincells, Inc. | Neurogenesis via modulation of the muscarinic receptors |
| EP2258357A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| EP1940389A2 (en) | 2005-10-21 | 2008-07-09 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| US20070112017A1 (en) | 2005-10-31 | 2007-05-17 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| AU2007249399A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| CA2651862A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | 5 ht receptor mediated neurogenesis |
| CN101490004B (zh) * | 2006-07-14 | 2012-01-11 | 奇斯药制品公司 | 作为磷酸二酯酶抑制剂的1-苯基-2-吡啶基烯基醇的衍生物 |
| WO2008030651A1 (en) | 2006-09-08 | 2008-03-13 | Braincells, Inc. | Combinations containing a 4-acylaminopyridine derivative |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| MX354786B (es) | 2007-06-04 | 2018-03-21 | Synergy Pharmaceuticals Inc | Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos. |
| EP2022783A1 (en) * | 2007-08-08 | 2009-02-11 | CHIESI FARMACEUTICI S.p.A. | "Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors" |
| EP2070913A1 (en) | 2007-12-14 | 2009-06-17 | CHIESI FARMACEUTICI S.p.A. | Ester derivatives as phosphodiesterase inhibitors |
| CA2930674A1 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| WO2010003084A2 (en) * | 2008-07-02 | 2010-01-07 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| CA2730603C (en) | 2008-07-16 | 2019-09-24 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP2196465A1 (en) | 2008-12-15 | 2010-06-16 | Almirall, S.A. | (3-oxo)pyridazin-4-ylurea derivatives as PDE4 inhibitors |
| WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| EP2226323A1 (en) | 2009-02-27 | 2010-09-08 | Almirall, S.A. | New tetrahydropyrazolo[3,4-c]isoquinolin-5-amine derivatives |
| EP2380890A1 (en) | 2010-04-23 | 2011-10-26 | Almirall, S.A. | New 7,8-dihydro-1,6-naphthyridin-5(6h)-one-derivatives as PDE4 inhibitors |
| EP2394998A1 (en) | 2010-05-31 | 2011-12-14 | Almirall, S.A. | 3-(5-Amino-6-oxo-1,6-dihydropyridazin-3-yl)-biphenyl derivatives as PDE4 inhibitors |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| WO2012118972A2 (en) | 2011-03-01 | 2012-09-07 | Synegy Pharmaceuticals Inc. | Process of preparing guanylate cyclase c agonists |
| JP2014518203A (ja) | 2011-06-06 | 2014-07-28 | キエスィ ファルマチェウティチ エス．ピー．エー． | ホスホジエステラーゼ阻害剤としての１−フェニル−２−ピリジニルアルキルアルコール誘導体 |
| CN103827088B (zh) | 2011-09-26 | 2017-10-13 | 奇斯药制品公司 | 作为磷酸二酯酶抑制剂的1‑苯基‑2‑吡啶基烷基醇的衍生物 |
| WO2013057013A2 (en) | 2011-10-21 | 2013-04-25 | Chiesi Farmaceutici S.P.A. | Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors |
| US20150119399A1 (en) | 2012-01-10 | 2015-04-30 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| EP2855450B1 (en) | 2012-06-04 | 2016-07-06 | Chiesi Farmaceutici S.p.A. | Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors |
| CN104822659A (zh) | 2012-12-05 | 2015-08-05 | 奇斯药制品公司 | 作为磷酸二酯酶抑制剂的1-苯基-2-吡啶基烷基醇衍生物 |
| EP3718557A3 (en) | 2013-02-25 | 2020-10-21 | Bausch Health Ireland Limited | Guanylate cyclase receptor agonist sp-333 for use in colonic cleansing |
| AU2014235215A1 (en) | 2013-03-15 | 2015-10-01 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| JP2016514670A (ja) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | 他の薬物と組み合わせたグアニル酸シクラーゼ受容体アゴニスト |
| CN113388007A (zh) | 2013-06-05 | 2021-09-14 | 博士医疗爱尔兰有限公司 | 鸟苷酸环化酶c的超纯激动剂、制备和使用所述激动剂的方法 |
| JP6694385B2 (ja) | 2013-08-09 | 2020-05-13 | アーデリクス，インコーポレーテッド | リン酸塩輸送阻害のための化合物及び方法 |
| CN114340631A (zh) | 2019-05-21 | 2022-04-12 | 阿德利克斯股份有限公司 | 用于降低患者的血清磷酸盐的组合 |
Family Cites Families (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1285932A (fr) * | 1960-12-26 | 1962-03-02 | Nord Aviation | Charge creuse |
| US3947467A (en) * | 1973-08-02 | 1976-03-30 | Eli Lilly And Company | 3-(5-Nitro-2-imidazolyl) pyrazoles |
| FR2257272B1 (cs) * | 1974-01-15 | 1978-08-25 | Pharmascience Labo | |
| DE2413935A1 (de) * | 1974-03-20 | 1975-10-16 | Schering Ag | 4-(polyalkoxy-phenyl)-2-pyrrolidone |
| US4193926A (en) * | 1974-03-20 | 1980-03-18 | Schering Aktiengesellschaft | 4-(Polyalkoxy phenyl)-2-pyrrolidones |
| DE2541855A1 (de) * | 1975-09-18 | 1977-03-31 | Schering Ag | 4-(polyalkoxy-phenyl)-2-pyrrolidone ii |
| FR2313422A2 (fr) * | 1975-06-02 | 1976-12-31 | Labaz | Nouveaux stabilisants des polymeres et copolymeres du chlorure de vinyle |
| SU888821A3 (ru) * | 1976-12-03 | 1981-12-07 | Шеринг Аг (Инофирма) | Способ получени 5-(замещенный фенил)-оксазолидинонов или их серусодержащих аналогов |
| DE2962383D1 (en) * | 1978-06-15 | 1982-05-06 | Ici Plc | Anti-inflammatory 1-phenyl-2-aminoethanol derivatives, pharmaceutical compositions thereof for topical use, and processes for their manufacture |
| DE3374313D1 (de) * | 1982-12-23 | 1987-12-10 | Smith Kline French Lab | Aminopyrimidinone derivatives as histamine h1-antagonists |
| IT1161221B (it) * | 1983-04-21 | 1987-03-18 | Ripharm Srl | Composto per il trattamento della psoriasi |
| ATE60591T1 (de) * | 1984-06-25 | 1991-02-15 | Ciba Geigy Ag | Pyrimidinderivate wirksam als schaedlingsbekaempfungsmittel. |
| US4876252A (en) * | 1986-01-13 | 1989-10-24 | American Cyanamid Company | 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines |
| ATE135699T1 (de) * | 1986-01-13 | 1996-04-15 | American Cyanamid Co | 4,5,6-substituierte 2-pyrimidinamine |
| US4788195A (en) * | 1986-01-13 | 1988-11-29 | American Cyanamid Company | 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines |
| US5128358A (en) * | 1988-01-19 | 1992-07-07 | Pfizer Inc. | Aryl substituted nitrogen heterocyclic antidepressants |
| WO1987006576A1 (en) * | 1986-04-29 | 1987-11-05 | Pfizer Inc. | Calcium independent camp phosphodiesterase inhibitor antidepressant |
| US4792561A (en) * | 1986-05-29 | 1988-12-20 | Syntex (U.S.A.) Inc. | Carbostyril derivatives as combined thromboxane synthetase and cyclic-AMP phosphodiesterase inhibitors |
| US4921862A (en) * | 1986-05-29 | 1990-05-01 | Syntex (U.S.A.) Inc. | Carbostyril derivatives as combined thromboxane synthetase and cyclic-amp phosphodiesterase inhibitors |
| CN1030415A (zh) * | 1987-02-20 | 1989-01-18 | 山之内制药株式会社 | 饱和的杂环碳酰胺衍生物和它的制备方法 |
| US5274002A (en) * | 1987-04-14 | 1993-12-28 | Warner-Lambert Company | Trisubstituted phenyl analogs having activity for congestive heart failure |
| US4971959A (en) * | 1987-04-14 | 1990-11-20 | Warner-Lambert Company | Trisubstituted phenyl analogs having activity for congestive heart failure |
| EP0295210B1 (de) * | 1987-06-11 | 1993-08-04 | Ciba-Geigy Ag | Mikrobizide |
| US4966622A (en) * | 1988-04-12 | 1990-10-30 | Ciba-Geigy Corporation | N-phenyl-N-pyrimidin-2-ylureas |
| US4897396A (en) * | 1988-06-03 | 1990-01-30 | Ciba-Geigy Corporation | 2-phenylamino pyrimidine derivatives and their uses as microbicides |
| EP0393500A1 (de) * | 1989-04-17 | 1990-10-24 | Byk Gulden Lomberg Chemische Fabrik GmbH | Neue Arylpyridazine, ihre Herstellung, Verwendung und sie enthaltende Arzneimittel |
| US5164372A (en) * | 1989-04-28 | 1992-11-17 | Fujisawa Pharmaceutical Company, Ltd. | Peptide compounds having substance p antagonism, processes for preparation thereof and pharmaceutical composition comprising the same |
| JPH0377923A (ja) * | 1989-08-18 | 1991-04-03 | Sekisui Chem Co Ltd | 有機非線形光学材料 |
| JPH075572B2 (ja) * | 1989-08-18 | 1995-01-25 | 積水化学工業株式会社 | ２―［２―（２―ヒドロキシフェニル）ビニルピラジンおよびその製造法 |
| DE4003919A1 (de) * | 1990-02-09 | 1991-08-14 | Basf Ag | Heteroarylalkene, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung |
| GB9007762D0 (en) * | 1990-04-05 | 1990-06-06 | Beecham Group Plc | Novel compounds |
| AU7854291A (en) * | 1990-04-27 | 1991-11-27 | Rorer International (Holdings), Inc. | Styryl compounds which inhibit egf receptor protein tyrosine kinase |
| FI930077A0 (fi) * | 1990-07-10 | 1993-01-08 | Smithkline Beecham Corp | Oxamider |
| US5124455A (en) * | 1990-08-08 | 1992-06-23 | American Home Products Corporation | Oxime-carbamates and oxime-carbonates as bronchodilators and anti-inflammatory agents |
| WO1992006085A1 (en) * | 1990-09-28 | 1992-04-16 | Smith Kline & French Laboratories Limited | Phenylpyridinol derivatives as medicaments |
| CA2094127A1 (en) * | 1990-10-16 | 1992-04-17 | Hermann Amschler | Arylpyridazinones |
| JPH06501708A (ja) * | 1990-11-06 | 1994-02-24 | スミスクライン・ビーチャム・コーポレイション | イミダゾリジノン化合物 |
| SE470395B (sv) * | 1990-12-05 | 1994-02-14 | Erik Lindgren Produktide Ab | Ryggstödjande anordning |
| GB9027055D0 (en) * | 1990-12-13 | 1991-02-06 | Sandoz Ltd | Organic compounds |
| IE71647B1 (en) * | 1991-01-28 | 1997-02-26 | Rhone Poulenc Rorer Ltd | Benzamide derivatives |
| US5698711A (en) * | 1991-01-28 | 1997-12-16 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| AU1574892A (en) * | 1991-04-26 | 1992-12-21 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Novel pyridazines |
| US5191084A (en) * | 1991-05-01 | 1993-03-02 | American Home Products Corporation | Phenyl pyrazolidinones as bronchodilators and anti-inflammatory agents |
| PT100441A (pt) * | 1991-05-02 | 1993-09-30 | Smithkline Beecham Corp | Pirrolidinonas, seu processo de preparacao, composicoes farmaceuticas que as contem e uso |
| EP0540165A1 (en) * | 1991-10-03 | 1993-05-05 | Zeneca Limited | Alkanoic acid derivatives |
| CA2080554A1 (en) * | 1991-10-15 | 1993-04-16 | Mitsubishi Chemical Corporation | Styrene derivatives |
| DE4136921A1 (de) * | 1991-11-11 | 1993-05-13 | Knoll Ag | Verfahren zur trennung von 5-methyl-tetrahydrofolsaeure |
| US5326898A (en) * | 1992-02-11 | 1994-07-05 | Allergan, Inc. | Substituted phenylethenyl compounds having retinoid-like biological activity |
| AU3738393A (en) * | 1992-04-02 | 1993-11-08 | Smithkline Beecham Corporation | Compounds useful for treating inflammatory diseases and for inhibiting production of tumor necrosis factor |
| US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| TW225528B (cs) * | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| GB9212693D0 (en) * | 1992-06-15 | 1992-07-29 | Celltech Ltd | Chemical compounds |
| GB9212673D0 (en) * | 1992-06-15 | 1992-07-29 | Celltech Ltd | Chemical compounds |
| ATE282025T1 (de) * | 1992-07-28 | 2004-11-15 | Aventis Pharma Ltd | Inhibitoren von c-amp phosphodiesterase |
| GB9222253D0 (en) * | 1992-10-23 | 1992-12-09 | Celltech Ltd | Chemical compounds |
| WO1994012461A1 (en) * | 1992-12-02 | 1994-06-09 | Pfizer Inc. | Catechol diethers as selective pdeiv inhibitors |
| ES2139676T3 (es) * | 1992-12-17 | 2000-02-16 | Pfizer | Pirazoles sustituidos como antagonistas del crf. |
| US5622977A (en) * | 1992-12-23 | 1997-04-22 | Celltech Therapeutics Limited | Tri-substituted (aryl or heteroaryl) derivatives and pharmaceutical compositions containing the same |
| TW263495B (cs) * | 1992-12-23 | 1995-11-21 | Celltech Ltd | |
| GB9226830D0 (en) * | 1992-12-23 | 1993-02-17 | Celltech Ltd | Chemical compounds |
| GB9304920D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9315595D0 (en) * | 1993-07-28 | 1993-09-08 | Res Inst Medicine Chem | New compounds |
| PT672042E (pt) * | 1993-10-01 | 2006-08-31 | Novartis Ag | Derivados de pirimidinoamina farmacologicamente activos e processos para a sua preparacao |
| CA2148931A1 (en) * | 1993-10-01 | 1995-04-13 | Jurg Zimmermann | Pyrimidineamine derivatives and processes for the preparation thereof |
| US5543520A (en) * | 1993-10-01 | 1996-08-06 | Ciba-Geigy Corporation | Pyrimidine derivatives |
| DK0672041T3 (da) * | 1993-10-01 | 2002-02-25 | Novartis Ag | Farmakologisk aktive pyridinderivater og fremgangsmåder til fremstilling deraf |
| DE69404044T2 (de) * | 1993-11-26 | 1997-10-16 | Pfizer | Isoxazolinverbindungen als entzündungshemmende mittel |
| GB9326173D0 (en) * | 1993-12-22 | 1994-02-23 | Celltech Ltd | Chemical compounds and process |
| GB9326600D0 (en) * | 1993-12-22 | 1994-03-02 | Celltech Ltd | Chemical compounds |
| WO1995017399A1 (en) * | 1993-12-22 | 1995-06-29 | Celltech Therapeutics Limited | Trisubstituted phenyl derivatives, processes for their preparation and their use as phosphodiesterase (type iv) inhibitors |
| US5691376A (en) * | 1994-02-17 | 1997-11-25 | American Home Products Corporation | Substituted biphenyl derivatives |
| US5559137A (en) * | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
| EP0764153A1 (en) * | 1994-06-06 | 1997-03-26 | Pfizer Inc. | Substituted pyrazoles having corticotropin-releasing factor (crf) antagonist activity |
| US5786354A (en) * | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
| US6245774B1 (en) * | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
| GB9412571D0 (en) * | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412573D0 (en) * | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412672D0 (en) * | 1994-06-23 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| WO1996020281A1 (en) * | 1994-12-23 | 1996-07-04 | Celltech Therapeutics Limited | Human phosphodiesterase type ivc, and its production and use |
| US5593997A (en) * | 1995-05-23 | 1997-01-14 | Pfizer Inc. | 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors |
| AU700637B2 (en) * | 1995-10-02 | 1999-01-07 | F. Hoffmann-La Roche Ag | Pyrimidine derivatives as 5ht2c-receptor antagonists |
| GB9526243D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526245D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526246D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9608435D0 (en) * | 1996-04-24 | 1996-06-26 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9625184D0 (en) * | 1996-12-04 | 1997-01-22 | Celltech Therapeutics Ltd | Chemical compounds |
-
1995
- 1995-06-20 US US08/492,639 patent/US5786354A/en not_active Expired - Fee Related
- 1995-06-21 SK SK1630-96A patent/SK282661B6/sk unknown
- 1995-06-21 DK DK95922633T patent/DK0770065T3/da active
- 1995-06-21 ES ES95922633T patent/ES2218548T3/es not_active Expired - Lifetime
- 1995-06-21 WO PCT/GB1995/001459 patent/WO1995035281A1/en active IP Right Grant
- 1995-06-21 NZ NZ288294A patent/NZ288294A/xx unknown
- 1995-06-21 AU AU27461/95A patent/AU707472B2/en not_active Ceased
- 1995-06-21 AT AT95922633T patent/ATE263153T1/de not_active IP Right Cessation
- 1995-06-21 CZ CZ19963730A patent/CZ293311B6/cs not_active IP Right Cessation
- 1995-06-21 CN CNB951937405A patent/CN1304372C/zh not_active Expired - Fee Related
- 1995-06-21 DE DE1995632808 patent/DE69532808T2/de not_active Expired - Fee Related
- 1995-06-21 JP JP50184396A patent/JP3856465B2/ja not_active Expired - Fee Related
- 1995-06-21 HU HU9603578A patent/HUT76803A/hu unknown
- 1995-06-21 EP EP95922633A patent/EP0770065B1/en not_active Expired - Lifetime
- 1995-06-21 PT PT95922633T patent/PT770065E/pt unknown
- 1995-06-21 RU RU97100794/04A patent/RU2201921C2/ru not_active IP Right Cessation
-
1996
- 1996-12-19 FI FI965126A patent/FI115302B/fi active IP Right Grant
- 1996-12-20 NO NO19965524A patent/NO312672B1/no unknown
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1998
- 1998-03-26 US US09/048,592 patent/US6077854A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES2218548T3 (es) | 2004-11-16 |
| CN1151732A (zh) | 1997-06-11 |
| FI965126A0 (fi) | 1996-12-19 |
| PT770065E (pt) | 2004-08-31 |
| NO965524D0 (no) | 1996-12-20 |
| WO1995035281A1 (en) | 1995-12-28 |
| CZ373096A3 (en) | 1997-08-13 |
| JPH10503173A (ja) | 1998-03-24 |
| DE69532808D1 (de) | 2004-05-06 |
| HUT76803A (en) | 1997-11-28 |
| FI115302B (fi) | 2005-04-15 |
| NO965524L (no) | 1996-12-20 |
| SK163096A3 (en) | 1997-10-08 |
| AU707472B2 (en) | 1999-07-08 |
| CZ293311B6 (cs) | 2004-03-17 |
| AU2746195A (en) | 1996-01-15 |
| CN1304372C (zh) | 2007-03-14 |
| FI965126A7 (fi) | 1996-12-19 |
| ATE263153T1 (de) | 2004-04-15 |
| EP0770065B1 (en) | 2004-03-31 |
| HU9603578D0 (en) | 1997-02-28 |
| SK282661B6 (sk) | 2002-11-06 |
| US6077854A (en) | 2000-06-20 |
| NZ288294A (en) | 1999-01-28 |
| US5786354A (en) | 1998-07-28 |
| RU2201921C2 (ru) | 2003-04-10 |
| DK0770065T3 (da) | 2004-07-19 |
| JP3856465B2 (ja) | 2006-12-13 |
| DE69532808T2 (de) | 2005-01-13 |
| EP0770065A1 (en) | 1997-05-02 |
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