EA019385B1 - ЗАМЕЩЕННЫЕ ИМИДАЗОЛЬНЫЕ ПРОИЗВОДНЫЕ, СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ РТРазы - Google Patents
ЗАМЕЩЕННЫЕ ИМИДАЗОЛЬНЫЕ ПРОИЗВОДНЫЕ, СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ РТРазы Download PDFInfo
- Publication number
- EA019385B1 EA019385B1 EA200870218A EA200870218A EA019385B1 EA 019385 B1 EA019385 B1 EA 019385B1 EA 200870218 A EA200870218 A EA 200870218A EA 200870218 A EA200870218 A EA 200870218A EA 019385 B1 EA019385 B1 EA 019385B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- phenyl
- dichlorophenyl
- dioxide
- ylmethyl
- thiadiazolidin
- Prior art date
Links
- 239000008194 pharmaceutical composition Chemical class 0.000 title claims abstract description 14
- 150000002460 imidazoles Chemical class 0.000 title abstract description 5
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title abstract description 5
- 239000003112 inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 72
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 10
- -1 1-propylbutyl Chemical group 0.000 claims description 191
- 239000000203 mixture Substances 0.000 claims description 68
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 53
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 27
- 239000011734 sodium Substances 0.000 claims description 14
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 239000003085 diluting agent Substances 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 4
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
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Classifications
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Landscapes
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| ZA200805648B (en) * | 2006-01-30 | 2009-09-30 | Transtech Pharma Inc | Substituted imidazole derivatives and their use as PTPase inhibitors |
| AU2010256360A1 (en) | 2009-06-05 | 2012-01-12 | Astrazeneca Ab | Aminopyrrolidinone derivatives and uses thereof |
| US20120135997A1 (en) | 2009-07-17 | 2012-05-31 | Shionogi & Co., Ltd. | Pharmaceutical composition comprising a lactam or benzenesulfonamide compound |
| JP5398076B2 (ja) * | 2009-12-10 | 2014-01-29 | 四国化成工業株式会社 | ２−（ブロモベンジル）−４−（ブロモフェニル）−５−メチルイミダゾール化合物 |
| JP5398075B2 (ja) * | 2010-01-13 | 2014-01-29 | 四国化成工業株式会社 | ４−（ジクロロフェニル）−２−（４−フルオロベンジル）−５−メチルイミダゾール化合物 |
| BR112013004882A2 (pt) | 2010-08-31 | 2016-05-03 | Snu R&Db Foundation | utilização de reprogramação fetal de agonista ppar delta |
| US9040525B2 (en) | 2010-10-08 | 2015-05-26 | Mochida Pharmaceutical Co., Ltd. | Cyclic amide derivative |
| WO2012094580A2 (en) | 2011-01-07 | 2012-07-12 | High Point Pharmaceuticals, Llc | Compounds that modulate oxidative stress |
| EP2716636A4 (en) | 2011-04-28 | 2014-11-26 | Mochida Pharm Co Ltd | CYCLIC AMIDE DERIVATIVE |
| US10696642B2 (en) | 2015-09-23 | 2020-06-30 | The General Hospital Corporation | TEAD transcription factor autopalmitoylation inhibitors |
| BR112018006866B1 (pt) | 2015-10-07 | 2023-11-21 | Mitobridge, Inc. | Compostos agonistas de ppar, composições farmacêuticas e métodos de uso dos mesmos |
| KR102430906B1 (ko) | 2016-04-13 | 2022-08-10 | 미토브리지, 인크. | Ppar 효능제, 화합물, 제약 조성물, 및 그의 사용 방법 |
| KR20230109185A (ko) | 2016-06-07 | 2023-07-19 | 자코바이오 파마슈티칼스 컴퍼니 리미티드 | Shp2 억제제로서 유용한 신규한 헤테로환형 유도체 |
| PT3601239T (pt) | 2017-03-23 | 2024-10-24 | Jacobio Pharmaceuticals Co Ltd | Novos derivados heterocíclicos úteis como inibidores de shp2 |
| EP3810580A1 (en) * | 2018-06-21 | 2021-04-28 | Calico Life Sciences LLC | Protein tyrosine phosphatase inhibitors and methods of use thereof |
| CN112839935A (zh) | 2018-09-26 | 2021-05-25 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
| CN119490431A (zh) | 2019-03-15 | 2025-02-21 | 总医院公司 | Tead转录因子的新型小分子抑制剂 |
| US11058695B2 (en) * | 2019-11-08 | 2021-07-13 | Myongji University Industry And Academia Cooperation Foundation | Inhibitor of carbapenem-hydrolyzing class D beta-lactamases |
| US20230265082A1 (en) * | 2020-08-10 | 2023-08-24 | Dana-Farber Cancer Institute, Inc. | Substituted 1,2,4-oxadiazoles as small molecule inhibitors of ubiquitin-specific protease 28 |
| WO2022076764A1 (en) * | 2020-10-09 | 2022-04-14 | Bristol-Myers Squibb Company | Aminoimidazole fpr2 agonists |
| WO2022078152A1 (zh) * | 2020-10-12 | 2022-04-21 | 杭州中美华东制药有限公司 | 苯并咪唑酮类glp-1受体激动剂及其用途 |
| CN117658947A (zh) * | 2022-09-06 | 2024-03-08 | 杭州中美华东制药有限公司 | 蛋白酪氨酸磷酸酶抑制作用的5-(取代芳基)-1,2,5-噻二唑啉-3-酮类化合物 |
Citations (2)
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|---|---|---|---|---|
| WO2005035551A2 (en) * | 2003-10-08 | 2005-04-21 | Incyte Corporation | Inhibitors of proteins that bind phosphorylated molecules |
| WO2005080346A1 (en) * | 2004-02-12 | 2005-09-01 | Transtech Pharma, Inc. | Substituted azole derivatives, compositions, and methods of use |
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| JPS63276054A (ja) | 1987-05-07 | 1988-11-14 | Hitachi Chem Co Ltd | 電子写真感光体 |
| DE69026851T2 (de) | 1989-02-14 | 1996-10-31 | Wako Pure Chem Ind Ltd | Verfahren zur Erhöhung von Chemilumineszenz |
| EP0553009B1 (fr) | 1992-01-23 | 1997-06-04 | Institut Francais Du Petrole | Catalyseur d'alkylation de paraffines |
| US5510362A (en) | 1992-03-13 | 1996-04-23 | Merck, Sharp And Dohme Limited | Imidazole, triazole and tetrazole derivatives |
| US5348969A (en) | 1992-04-03 | 1994-09-20 | Bristol-Myers Squibb Company | Diphenyloxazolyl-oxazoles as platelet aggregation inhibitors |
| AU5118893A (en) | 1992-10-13 | 1994-05-09 | Nippon Soda Co., Ltd. | Oxazole and thiazole derivatives |
| ATE202571T1 (de) | 1993-09-14 | 2001-07-15 | Merck & Co Inc | Humane protein-tyrosinphosphatase decodierende cdna |
| US5616601A (en) | 1994-07-28 | 1997-04-01 | Gd Searle & Co | 1,2-aryl and heteroaryl substituted imidazolyl compounds for the treatment of inflammation |
| US5700816A (en) | 1995-06-12 | 1997-12-23 | Isakson; Peter C. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor |
| CA2224517A1 (en) | 1995-06-12 | 1996-12-27 | G.D. Searle & Co. | Compositions comprising a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor |
| US5753687A (en) | 1995-06-19 | 1998-05-19 | Ontogen Corporation | Modulators of proteins with phosphotryrosine recognition units |
| US6388076B1 (en) | 1995-06-19 | 2002-05-14 | Ontogen Corporation | Protein tyrosine phosphatase-inhibiting compounds |
| JP3849157B2 (ja) | 1995-08-01 | 2006-11-22 | 東ソー株式会社 | ２−イミダゾリン類の製造法 |
| US6238902B1 (en) | 1996-03-22 | 2001-05-29 | Genentech, Inc. | Protein tyrosine phosphatases |
| US5958957A (en) | 1996-04-19 | 1999-09-28 | Novo Nordisk A/S | Modulators of molecules with phosphotyrosine recognition units |
| CA2275610A1 (en) * | 1996-12-16 | 1998-06-25 | Ontogen Corporation | Modulators of proteins with phosphotyrosine recognition units |
| US5840721A (en) | 1997-07-09 | 1998-11-24 | Ontogen Corporation | Imidazole derivatives as MDR modulators |
| GB9715816D0 (en) | 1997-07-25 | 1997-10-01 | Black James Foundation | Histamine H receptor ligands |
| FR2767527B1 (fr) | 1997-08-25 | 1999-11-12 | Pf Medicament | Derives de piperazines indoliques, utiles comme medicaments et procede de preparation |
| JP2001514245A (ja) | 1997-08-28 | 2001-09-11 | ファルマシア・アンド・アップジョン・カンパニー | タンパク質チロシンホスファターゼ阻害剤 |
| EP1017697A1 (en) | 1997-09-23 | 2000-07-12 | Novo Nordisk A/S | MODULES OF PROTEIN TYROSINE PHOSPHATASES (PTPases) |
| US5972986A (en) | 1997-10-14 | 1999-10-26 | G.D. Searle & Co. | Method of using cyclooxygenase-2 inhibitors in the treatment and prevention of neoplasia |
| US6159944A (en) * | 1998-02-27 | 2000-12-12 | Synchroneuron, Llc | Method for treating painful conditions of the anal region and compositions therefor |
| US20020002199A1 (en) | 1998-03-12 | 2002-01-03 | Lone Jeppesen | Modulators of protein tyrosine phosphatases (ptpases) |
| US6262044B1 (en) | 1998-03-12 | 2001-07-17 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases (PTPASES) |
| US6699896B1 (en) | 1998-05-12 | 2004-03-02 | Wyeth | Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia |
| CA2331056A1 (en) | 1998-05-12 | 1999-12-02 | Wyeth | 2,3,5-substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia |
| US20030194745A1 (en) | 1998-06-26 | 2003-10-16 | Mcdowell Robert S. | Cysteine mutants and methods for detecting ligand binding to biological molecules |
| CA2338643A1 (en) | 1998-07-24 | 2000-02-10 | Merck Frosst Canada & Co./Merck Frosst Canada & Cie | Protein tyrosine phosphatase-1b (ptp-1b) deficient mice and uses thereof |
| US6174874B1 (en) | 1998-09-21 | 2001-01-16 | Merck Frosst Canada & Co. | Phosphonic acids derivatives as inhibitors of protein tyrosine phosphate 1B (PTP-1B) |
| CA2353997A1 (en) | 1998-12-11 | 2000-06-22 | Mcgill University | Therapeutic and diagnostic uses of protein tyrosine phosphatase tc-ptp |
| JP4221129B2 (ja) | 1999-02-15 | 2009-02-12 | 富士フイルム株式会社 | 含窒素ヘテロ環化合物、有機発光素子材料、有機発光素子 |
| EP1181309A1 (en) | 1999-05-14 | 2002-02-27 | Merck Frosst Canada Inc. | Phosphonic and carboxylic acid derivatives as inhibitors of protein tyrosine phosphatase-1b (ptp-1b) |
| PT1070708E (pt) | 1999-07-21 | 2004-05-31 | Hoffmann La Roche | Derivados de triazol |
| ES2252058T3 (es) | 1999-08-27 | 2006-05-16 | Sugen, Inc. | Mimicos de fosfato y metodos de tratamiento empleando inhibidores de fosfatasa. |
| US6410556B1 (en) | 1999-09-10 | 2002-06-25 | Novo Nordisk A/S | Modulators of protein tyrosine phosphateses (PTPases) |
| ATE312820T1 (de) | 1999-10-28 | 2005-12-15 | Trine Pharmaceuticals Inc | Pumpeninhibitoren zur freisetzung von medikamenten |
| US6624182B1 (en) | 1999-11-25 | 2003-09-23 | Ciba Specialty Chemicals Corporation | Hydroxyphenylvinylthiazoles |
| CA2393359A1 (en) | 1999-12-22 | 2001-06-28 | Merck Frosst Canada & Co. | Aromatic phosphonates as protein tyrosine phosphatase 1b (ptp-1b) inhibitors |
| AU2336001A (en) | 1999-12-22 | 2001-07-03 | Merck Frosst Canada & Co. | Phosphonic acid derivatives as inhibitors of protein tyrosine phosphatase 1b (ptp-1b) |
| EP1242432A1 (en) | 1999-12-22 | 2002-09-25 | Merck Frosst Canada Inc. | Phosphonic acid derivatives as inhibitors of protein tyrosine phosphatase 1b (ptp-1b) |
| US6777433B2 (en) | 1999-12-22 | 2004-08-17 | Merck Frosst Canada & Co. | Protein tyrosine phosphatase 1B (PTP-1B) inhibitors containing two ortho-substituted aromatic phosphonates |
| AU2335701A (en) | 1999-12-22 | 2001-07-03 | Merck Frosst Canada & Co. | Phosphonic acid biaryl derivatives as inhibitors of protein tyrosine phosphatase 1B (PTP-1B) |
| JP2003520049A (ja) | 2000-01-18 | 2003-07-02 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | ヒトタンパク質であるチロシンホスファターゼのポリヌクレオチド、ポリペプチド、および抗体 |
| TWI284639B (en) | 2000-01-24 | 2007-08-01 | Shionogi & Co | A compound having thrombopoietin receptor agonistic effect |
| US20020009762A1 (en) | 2000-02-14 | 2002-01-24 | Flint Andrew J. | Assay for protein tyrosine phosphatases |
| JP2003528107A (ja) | 2000-03-22 | 2003-09-24 | メルク フロスト カナダ アンド カンパニー | Ｐｔｐ−１ｂ阻害薬としての硫黄置換アリールジフルオロメチルホスホン酸類 |
| US6627647B1 (en) | 2000-03-23 | 2003-09-30 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted 1-(4-aminophenyl)imidazoles and their use as anti-inflammatory agents |
| US6911468B2 (en) | 2000-05-22 | 2005-06-28 | Takeda Chemical Industries, Ltd. | Tyrosine phosphatase inhibitors |
| AU2001278188B2 (en) | 2000-07-06 | 2007-05-17 | Amgen Inc. | Tyrosine derivatives as phosphatase inhibitors |
| US6613903B2 (en) | 2000-07-07 | 2003-09-02 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases (PTPases) |
| US20020099073A1 (en) | 2000-07-07 | 2002-07-25 | Andersen Henrik Sune | Modulators of protein tyrosine phosphatases (PTPases) |
| US6627767B2 (en) | 2000-08-29 | 2003-09-30 | Abbott Laboratories | Amino(oxo) acetic acid protein tyrosine phosphatase inhibitors |
| US6472545B2 (en) | 2000-08-29 | 2002-10-29 | Abbott Laboratories | Protein tyrosine phosphatase inhibitors |
| US6972340B2 (en) | 2000-08-29 | 2005-12-06 | Abbott Laboratories | Selective protein tyrosine phosphatatase inhibitors |
| US20020169157A1 (en) | 2000-08-29 | 2002-11-14 | Gang Liu | Selective protein tyrosine phosphatatase inhibitors |
| US20020035137A1 (en) | 2000-08-29 | 2002-03-21 | Gang Liu | Amino (oxo) acetic acid protein tyrosine phosphatase inhibitors |
| GB0022079D0 (en) | 2000-09-08 | 2000-10-25 | Inst Of Molecul & Cell Biology | Novel protein tyrosine phosphatase inhibitor |
| JP2002114768A (ja) | 2000-10-11 | 2002-04-16 | Japan Tobacco Inc | ２−（２，５−ジハロゲン−３，４−ジヒドロキシフェニル）アゾール化合物及びそれを含有してなる医薬組成物 |
| US20030108883A1 (en) | 2001-02-13 | 2003-06-12 | Rondinone Cristina M. | Methods for identifying compounds that inhibit or reduce PTP1B expression |
| US20030120073A1 (en) | 2001-04-25 | 2003-06-26 | Seto Christopher T. | Alpha-ketocarboxylic acid based inhibitors of phosphoryl tyrosine phosphatases |
| JP2002322054A (ja) | 2001-04-26 | 2002-11-08 | Dai Ichi Seiyaku Co Ltd | 薬剤排出ポンプ阻害薬 |
| US7163932B2 (en) | 2001-06-20 | 2007-01-16 | Merck Frosst Canada & Co. | Aryldifluoromethylphosphonic acids for treatment of diabetes |
| US20030064979A1 (en) | 2001-06-29 | 2003-04-03 | Hansen Thomas Kruse | Method of inhibiting PTP 1B and /or T-cell PTP and/or other PTPases with an Asp residue at position 48 |
| US20030170660A1 (en) | 2001-07-11 | 2003-09-11 | Sondergaard Helle Bach | P387L variant in protein tyrosine phosphatase-1B is associated with type 2 diabetes and impaired serine phosphorylation of PTP-1B in vitro |
| CA2463441A1 (en) | 2001-10-12 | 2003-05-08 | Bayer Pharmaceuticals Corporation | Phenyl substituted 5-membered nitrogen containing heterocycles for the treatment of obesity |
| US7022730B2 (en) | 2001-10-19 | 2006-04-04 | Transtech Pharma, Inc. | Bis-heteroaryl alkanes as therapeutic agents |
| WO2003033496A1 (en) | 2001-10-19 | 2003-04-24 | Transtech Pharma, Inc. | Beta-carbolin derivatives as ptp-inhibitors |
| JP2003231679A (ja) | 2001-12-03 | 2003-08-19 | Japan Tobacco Inc | アゾール化合物及びその医薬用途 |
| EP1452530A4 (en) | 2001-12-03 | 2005-11-30 | Japan Tobacco Inc | AZOL CONNECTION AND THEIR MEDICAL USE |
| US6642381B2 (en) | 2001-12-27 | 2003-11-04 | Hoffman-La Roche Inc. | Pyrimido[5,4-e][1,2,4]triazine-5,7-diamine compounds as protein tyrosine phosphatase inhibitors |
| US20030180827A1 (en) | 2002-01-04 | 2003-09-25 | Aventis Pharma Deutschland Gmbh. | Highly sensitive and continuous protein tyrosine phosphatase test using 6,8-difluoro-4-methylumbelliferyl phosphate |
| US20030215899A1 (en) | 2002-02-13 | 2003-11-20 | Ceptyr, Inc. | Reversible oxidation of protein tyrosine phosphatases |
| US6784205B2 (en) | 2002-03-01 | 2004-08-31 | Sunesis Pharmaceuticals, Inc. | Compounds that modulate the activity of PTP-1B and TC-PTP |
| CN101613321A (zh) | 2002-03-05 | 2009-12-30 | 特兰斯泰克制药公司 | 抑制配体与高级糖化终产物受体相互作用的单和双环吡咯衍生物 |
| NZ535545A (en) | 2002-04-03 | 2007-06-29 | Novartis Ag | 5-substituted 1,1-dioxo-1,2,5-thiazolidine-3-one derivatives as PTPase 1B inhibitors |
| BR0309305A (pt) | 2002-04-12 | 2005-02-15 | Pfizer | Compostos de imidazol como agentes antiinflamatórios e analgésicos |
| JP4529342B2 (ja) | 2002-04-23 | 2010-08-25 | 東ソー株式会社 | 環状アミジニウム有機酸塩の製造方法 |
| JP2003313172A (ja) | 2002-04-23 | 2003-11-06 | Tosoh Corp | Ｎ−置換イミダゾール化合物の製造方法 |
| AU2003228744A1 (en) | 2002-04-29 | 2003-11-17 | The Ohio State University | Inhibition of protein tyrosine phosphatases and sh2 domains by a neutral phosphotyrosine mimetic |
| US20040009946A1 (en) | 2002-05-23 | 2004-01-15 | Ceptyr, Inc. | Modulation of PTP1B expression and signal transduction by RNA interference |
| US6849761B2 (en) | 2002-09-05 | 2005-02-01 | Wyeth | Substituted naphthoic acid derivatives useful in the treatment of insulin resistance and hyperglycemia |
| EP1402888A1 (en) | 2002-09-18 | 2004-03-31 | Jerini AG | The use of substituted carbocyclic compounds as rotamases inhibitors |
| WO2004062664A1 (en) | 2002-12-30 | 2004-07-29 | Vertex Pharmaceuticals Incorporated | Sulfhydantoins as phosphate isosteres for use as phosphatase inhibitors in the treatment of cancer and autoimmune disorders |
| US7144911B2 (en) | 2002-12-31 | 2006-12-05 | Deciphera Pharmaceuticals Llc | Anti-inflammatory medicaments |
| US7279576B2 (en) | 2002-12-31 | 2007-10-09 | Deciphera Pharmaceuticals, Llc | Anti-cancer medicaments |
| US20040186151A1 (en) | 2003-02-12 | 2004-09-23 | Mjalli Adnan M.M. | Substituted azole derivatives as therapeutic agents |
| WO2004071447A2 (en) | 2003-02-12 | 2004-08-26 | Transtech Pharma Inc. | Substituted azole derivatives as therapeutic agents |
| US20040167188A1 (en) | 2003-02-14 | 2004-08-26 | Zhili Xin | Protein-tyrosine phosphatase inhibitors and uses thereof |
| TW200500362A (en) | 2003-04-09 | 2005-01-01 | Japan Tobacco Inc | 5-membered heteroaromatic ring compound and pharmaceutical use thereof |
| CN101321743A (zh) * | 2005-12-08 | 2008-12-10 | 诺瓦提斯公司 | 作为ptp-酶抑制剂的1,1,3-三氧代-1,2,5-噻二唑烷和它们的用途 |
| US8119666B2 (en) * | 2005-12-08 | 2012-02-21 | Novartis Ag | 1,2,5-thiazolidine derivatives useful for treating conditions mediated by protein tyrosine phosphatases (PTPase) |
| ZA200805648B (en) * | 2006-01-30 | 2009-09-30 | Transtech Pharma Inc | Substituted imidazole derivatives and their use as PTPase inhibitors |
-
2007
- 2007-01-30 ZA ZA200805648A patent/ZA200805648B/xx unknown
- 2007-01-30 AU AU2007211319A patent/AU2007211319B9/en not_active Ceased
- 2007-01-30 WO PCT/US2007/002675 patent/WO2007089857A2/en not_active Ceased
- 2007-01-30 US US11/699,780 patent/US7723369B2/en not_active Expired - Fee Related
- 2007-01-30 JP JP2008553332A patent/JP5180099B2/ja not_active Expired - Fee Related
- 2007-01-30 EA EA200870218A patent/EA019385B1/ru not_active IP Right Cessation
- 2007-01-30 KR KR1020087021180A patent/KR20080094806A/ko not_active Ceased
- 2007-01-30 CN CN2007800039423A patent/CN101374835B/zh not_active Expired - Fee Related
- 2007-01-30 NZ NZ569329A patent/NZ569329A/en not_active IP Right Cessation
- 2007-01-30 BR BRPI0707338-0A patent/BRPI0707338A2/pt not_active IP Right Cessation
- 2007-01-30 EP EP07763040.8A patent/EP1991544B1/en active Active
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- 2010-01-11 US US12/685,178 patent/US8404731B2/en not_active Expired - Fee Related
-
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- 2012-03-06 US US13/412,747 patent/US20120196906A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005035551A2 (en) * | 2003-10-08 | 2005-04-21 | Incyte Corporation | Inhibitors of proteins that bind phosphorylated molecules |
| WO2005080346A1 (en) * | 2004-02-12 | 2005-09-01 | Transtech Pharma, Inc. | Substituted azole derivatives, compositions, and methods of use |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20080094806A (ko) | 2008-10-24 |
| WO2007089857A3 (en) | 2008-06-26 |
| ZA200805648B (en) | 2009-09-30 |
| US20120196906A1 (en) | 2012-08-02 |
| EP1991544A2 (en) | 2008-11-19 |
| CN101374835B (zh) | 2012-04-25 |
| AU2007211319B2 (en) | 2012-01-19 |
| CA2637024C (en) | 2013-05-14 |
| AU2007211319B9 (en) | 2012-05-31 |
| BRPI0707338A2 (pt) | 2011-05-03 |
| EA200870218A1 (ru) | 2009-02-27 |
| IL192557A0 (en) | 2009-02-11 |
| WO2007089857A2 (en) | 2007-08-09 |
| IL192557A (en) | 2013-09-30 |
| CA2637024A1 (en) | 2007-08-09 |
| US20070191385A1 (en) | 2007-08-16 |
| US8404731B2 (en) | 2013-03-26 |
| NZ569329A (en) | 2011-09-30 |
| EP1991544B1 (en) | 2018-08-15 |
| AU2007211319A1 (en) | 2007-08-09 |
| US7723369B2 (en) | 2010-05-25 |
| HK1127342A1 (en) | 2009-09-25 |
| US20100113331A1 (en) | 2010-05-06 |
| JP5180099B2 (ja) | 2013-04-10 |
| JP2009525340A (ja) | 2009-07-09 |
| CN101374835A (zh) | 2009-02-25 |
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