ZA200510294B - Hexahydropyridoisoquinolines as DPP-IV inhibitors - Google Patents
Hexahydropyridoisoquinolines as DPP-IV inhibitors Download PDFInfo
- Publication number
- ZA200510294B ZA200510294B ZA200510294A ZA200510294A ZA200510294B ZA 200510294 B ZA200510294 B ZA 200510294B ZA 200510294 A ZA200510294 A ZA 200510294A ZA 200510294 A ZA200510294 A ZA 200510294A ZA 200510294 B ZA200510294 B ZA 200510294B
- Authority
- ZA
- South Africa
- Prior art keywords
- pyrido
- dimethoxy
- hexahydro
- ylamine
- isoquinolin
- Prior art date
Links
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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
- C07D401/08—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 carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
- C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03013405 | 2003-06-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200510294B true ZA200510294B (en) | 2006-12-27 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200510294A ZA200510294B (en) | 2003-06-20 | 2005-12-19 | Hexahydropyridoisoquinolines as DPP-IV inhibitors |
Country Status (21)
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|---|---|
| US (1) | US7718666B2 (es) |
| EP (1) | EP1638968B1 (es) |
| JP (1) | JP4445504B2 (es) |
| KR (1) | KR100744893B1 (es) |
| CN (1) | CN101090901B (es) |
| AR (1) | AR044796A1 (es) |
| AT (1) | ATE437876T1 (es) |
| AU (1) | AU2004251829B2 (es) |
| BR (1) | BRPI0411509A (es) |
| CA (1) | CA2528784C (es) |
| CO (1) | CO5640136A2 (es) |
| DE (1) | DE602004022294D1 (es) |
| ES (1) | ES2327740T3 (es) |
| IL (1) | IL172330A (es) |
| MX (1) | MXPA05013734A (es) |
| NO (1) | NO20055680L (es) |
| NZ (1) | NZ543863A (es) |
| RU (1) | RU2339636C2 (es) |
| TW (1) | TW200504063A (es) |
| WO (1) | WO2005000846A1 (es) |
| ZA (1) | ZA200510294B (es) |
Families Citing this family (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1406873B1 (en) | 2001-06-27 | 2007-09-26 | Smithkline Beecham Corporation | Fluoropyrrolidines as dipeptidyl peptidase inhibitors |
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| US20040242566A1 (en) | 2003-03-25 | 2004-12-02 | Syrrx, Inc. | Dipeptidyl peptidase inhibitors |
| US7169926B1 (en) | 2003-08-13 | 2007-01-30 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| CN1867560A (zh) | 2003-08-13 | 2006-11-22 | 武田药品工株式会社 | 4－嘧啶酮衍生物及其作为肽基肽酶抑制剂的用途 |
| US7678909B1 (en) | 2003-08-13 | 2010-03-16 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| EP1699777B1 (en) | 2003-09-08 | 2012-12-12 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
| US7732446B1 (en) | 2004-03-11 | 2010-06-08 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| CN102127053A (zh) | 2004-03-15 | 2011-07-20 | 武田药品工业株式会社 | 二肽基肽酶抑制剂 |
| US7687638B2 (en) | 2004-06-04 | 2010-03-30 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| WO2006019965A2 (en) | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| CN101107247B (zh) * | 2004-11-30 | 2011-10-19 | 霍夫曼-拉罗奇有限公司 | 作为用于治疗糖尿病的dpp-iv抑制剂的取代的苯并喹嗪衍生物 |
| EP2805953B1 (en) | 2004-12-21 | 2016-03-09 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| EP1917001A2 (en) * | 2005-08-11 | 2008-05-07 | F.Hoffmann-La Roche Ag | Pharmaceutical composition comprising a dpp-iv inhibitor |
| ME02005B (me) | 2005-09-14 | 2012-08-31 | Takeda Pharmaceuticals Co | Inhibitori dipeptidil peptidaze za lečenje dijabetesa |
| CA2622642C (en) | 2005-09-16 | 2013-12-31 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| WO2007112347A1 (en) | 2006-03-28 | 2007-10-04 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| ES2354390T3 (es) | 2006-04-11 | 2011-03-14 | Arena Pharmaceuticals, Inc. | Procedimientos de uso del receptor gpr119 para identificar compuestos útiles para aumentar la masa ósea en un individuo. |
| PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| EP2007734A1 (en) | 2006-04-12 | 2008-12-31 | Probiodrug AG | Enzyme inhibitors |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
| CN109503584A (zh) | 2006-05-04 | 2019-03-22 | 勃林格殷格翰国际有限公司 | 多晶型 |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| US8324383B2 (en) | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
| WO2008031750A2 (en) * | 2006-09-15 | 2008-03-20 | F. Hoffmann-La Roche Ag | Process for the preparation of pyrido[2,1-a]isoquinoline derivatives by catalytic asymmetric hydrogenation of an enamine |
| WO2008031749A1 (en) * | 2006-09-15 | 2008-03-20 | F. Hoffmann-La Roche Ag | Process for the preparation of pyrido[2,1-a]isoquinoline derivatives comprising optical resolution of an enamine |
| WO2008055945A1 (en) | 2006-11-09 | 2008-05-15 | Probiodrug Ag | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
| TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| US9126987B2 (en) | 2006-11-30 | 2015-09-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| US8093236B2 (en) | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
| EP2865670B1 (en) | 2007-04-18 | 2017-01-11 | Probiodrug AG | Thiourea derivatives as glutaminyl cyclase inhibitors |
| PE20091730A1 (es) | 2008-04-03 | 2009-12-10 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
| EP2146210A1 (en) | 2008-04-07 | 2010-01-20 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY |
| BRPI0916997A2 (pt) | 2008-08-06 | 2020-12-15 | Boehringer Ingelheim International Gmbh | Inibidor de dpp-4 e seu uso |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| MX2011002558A (es) | 2008-09-10 | 2011-04-26 | Boehringer Ingelheim Int | Terapia de combinacion para el tratamiento de diabetes y estados relacionados. |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
| EA022310B1 (ru) | 2008-12-23 | 2015-12-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Солевые формы органического соединения |
| AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
| AR077642A1 (es) | 2009-07-09 | 2011-09-14 | Arena Pharm Inc | Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo |
| EP2475428B1 (en) | 2009-09-11 | 2015-07-01 | Probiodrug AG | Heterocylcic derivatives as inhibitors of glutaminyl cyclase |
| KR20120092141A (ko) * | 2009-10-29 | 2012-08-20 | 서트리스 파마슈티컬즈, 인코포레이티드 | 시르투인 조절제로서의 비시클릭 피리딘 및 유사체 |
| MX364651B (es) | 2009-11-27 | 2019-05-03 | Boehringer Ingelheim Int Gmbh Star | Inhibidores de dpp-iv, tales como la linagliptina, y composiciones farmacéuticas o combinaciones que comprenden los mismos, para usarse en el tratamiento de pacientes diabéticos tipificados genéticamente. |
| US9181233B2 (en) | 2010-03-03 | 2015-11-10 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| AU2011226074B2 (en) | 2010-03-10 | 2015-01-22 | Vivoryon Therapeutics N.V. | Heterocyclic inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5) |
| CN102918027A (zh) | 2010-04-06 | 2013-02-06 | 艾尼纳制药公司 | Gpr119受体调节剂和对与所述受体有关的障碍的治疗 |
| WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
| EP2566469B1 (en) | 2010-05-05 | 2022-12-21 | Boehringer Ingelheim International GmbH | Combination therapy |
| EA201991014A1 (ru) | 2010-06-24 | 2019-09-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Лечение диабета |
| AU2011305525B2 (en) | 2010-09-22 | 2016-08-18 | Arena Pharmaceuticals, Inc. | Modulators of the GPR119 receptor and the treatment of disorders related thereto |
| AR083878A1 (es) | 2010-11-15 | 2013-03-27 | Boehringer Ingelheim Int | Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento |
| DK2686313T3 (en) | 2011-03-16 | 2016-05-02 | Probiodrug Ag | Benzimidazole derivatives as inhibitors of glutaminyl cyclase |
| US20140018371A1 (en) | 2011-04-01 | 2014-01-16 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| WO2012145361A1 (en) | 2011-04-19 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US20140038889A1 (en) | 2011-04-22 | 2014-02-06 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| US20140051714A1 (en) | 2011-04-22 | 2014-02-20 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| WO2012170702A1 (en) | 2011-06-08 | 2012-12-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US8883800B2 (en) | 2011-07-15 | 2014-11-11 | Boehringer Ingelheim International Gmbh | Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions |
| WO2013055910A1 (en) | 2011-10-12 | 2013-04-18 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| WO2013171167A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
| WO2014074668A1 (en) | 2012-11-08 | 2014-05-15 | Arena Pharmaceuticals, Inc. | Modulators of gpr119 and the treatment of disorders related thereto |
| WO2015128453A1 (en) | 2014-02-28 | 2015-09-03 | Boehringer Ingelheim International Gmbh | Medical use of a dpp-4 inhibitor |
| CN104478777B (zh) * | 2015-01-13 | 2016-08-24 | 佛山市赛维斯医药科技有限公司 | 一种含硝基金刚烷和酰胺结构的衍生物、其制备方法和用途 |
| WO2016127133A1 (en) * | 2015-02-06 | 2016-08-11 | Neurocrine Biosciences, Inc. | [9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido-[2,1-a]isoquinolin-2-yl]methanol and compounds, compositions and methods relating thereto |
| JP2018507914A (ja) | 2015-03-09 | 2018-03-22 | インテクリン・セラピューティクス・インコーポレイテッド | 非アルコール性脂肪肝疾患および／またはリポジストロフィーの処置のための方法 |
| WO2017211979A1 (en) | 2016-06-10 | 2017-12-14 | Boehringer Ingelheim International Gmbh | Combinations of linagliptin and metformin |
| JP2020515639A (ja) | 2017-04-03 | 2020-05-28 | コヒラス・バイオサイエンシズ・インコーポレイテッド | 進行性核上性麻痺の処置のためのＰＰＡＲγアゴニスト |
| JOP20190239A1 (ar) | 2017-04-19 | 2019-10-09 | Neurocrine Biosciences Inc | مركبات مثبطة لـ vmat2 وتركيبات منها |
| DK3461819T3 (da) | 2017-09-29 | 2020-08-10 | Probiodrug Ag | Inhibitorer af glutaminylcyklase |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8302499D0 (en) * | 1983-01-29 | 1983-03-02 | Wyeth John & Brother Ltd | Benzoquinolizines |
| US5681956A (en) | 1990-12-28 | 1997-10-28 | Neurogen Corporation | 4-aryl substituted piperazinylmethyl phenylimidazole derivatives; a new class of dopamine receptor subtype specific ligands |
| ZA925324B (en) | 1991-07-17 | 1994-07-17 | Syntex Inc | Decahydro-8h-isoquino Ú2,1-g¾ Ú1,6¾naphthyridine and decahydrobenzo Úa¾pyrrolo Ú2,3-e¾quinolizine derivatives |
| GB9313913D0 (en) | 1993-07-06 | 1993-08-18 | Smithkline Beecham Plc | Novel compounds |
| US5455351A (en) | 1993-12-13 | 1995-10-03 | Abbott Laboratories | Retroviral protease inhibiting piperazine compounds |
| DE122010000020I1 (de) | 1996-04-25 | 2010-07-08 | Prosidion Ltd | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
| TW492957B (en) | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
| US6011155A (en) | 1996-11-07 | 2000-01-04 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| ES2288807T1 (es) | 1998-02-02 | 2008-02-01 | Trustees Of Tufts College | Uso de inhibidores de dipeptidasa para regular el metabolismo de la glucosa. |
| DE19834591A1 (de) | 1998-07-31 | 2000-02-03 | Probiodrug Ges Fuer Arzneim | Verfahren zur Steigerung des Blutglukosespiegels in Säugern |
| GB9817118D0 (en) | 1998-08-07 | 1998-10-07 | Glaxo Group Ltd | Pharmaceutical compounds |
| CO5150173A1 (es) | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
| US6172081B1 (en) * | 1999-06-24 | 2001-01-09 | Novartis Ag | Tetrahydroisoquinoline 3-carboxamide derivatives |
| US6110949A (en) | 1999-06-24 | 2000-08-29 | Novartis Ag | N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| WO2001019805A1 (fr) | 1999-09-10 | 2001-03-22 | Takeda Chemical Industries, Ltd. | Composes heterocycliques et procede de preparation de ces derniers |
| WO2001034594A1 (en) | 1999-11-12 | 2001-05-17 | Guilford Pharmaceuticals, Inc. | Dipeptidyl peptidase iv inhibitors and methods of making and using dipeptidyl peptidase iv inhibitors |
| GB9928330D0 (en) | 1999-11-30 | 2000-01-26 | Ferring Bv | Novel antidiabetic agents |
| WO2001055105A1 (en) | 2000-01-24 | 2001-08-02 | Novo Nordisk A/S | N-substituted 2-cyanopyroles and -pyrrolines which are inhibitors of the enzyme dpp-iv |
| WO2001062266A2 (en) | 2000-02-25 | 2001-08-30 | Novo Nordisk A/S | Use of dpp-iv inhibitors for the treatment of diabetes |
| PT1323710E (pt) | 2000-10-06 | 2008-11-25 | Mitsubishi Tanabe Pharma Corp | Compostos azotados com anel de cinco membros |
| US6727261B2 (en) * | 2001-12-27 | 2004-04-27 | Hoffman-La Roche Inc. | Pyrido[2,1-A]Isoquinoline derivatives |
| DE602004030244D1 (de) | 2003-06-20 | 2011-01-05 | Hoffmann La Roche | Itoren |
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2004
- 2004-06-11 MX MXPA05013734A patent/MXPA05013734A/es active IP Right Grant
- 2004-06-11 ES ES04739825T patent/ES2327740T3/es active Active
- 2004-06-11 AT AT04739825T patent/ATE437876T1/de active
- 2004-06-11 NZ NZ543863A patent/NZ543863A/en unknown
- 2004-06-11 RU RU2006101457/04A patent/RU2339636C2/ru not_active IP Right Cessation
- 2004-06-11 WO PCT/EP2004/006336 patent/WO2005000846A1/en active Application Filing
- 2004-06-11 CA CA2528784A patent/CA2528784C/en not_active Expired - Fee Related
- 2004-06-11 DE DE602004022294T patent/DE602004022294D1/de active Active
- 2004-06-11 KR KR1020057024368A patent/KR100744893B1/ko not_active IP Right Cessation
- 2004-06-11 CN CN2004800173556A patent/CN101090901B/zh not_active Expired - Fee Related
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- 2004-06-11 JP JP2006515909A patent/JP4445504B2/ja not_active Expired - Fee Related
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- 2004-06-11 EP EP04739825A patent/EP1638968B1/en not_active Not-in-force
- 2004-06-16 TW TW093117359A patent/TW200504063A/zh unknown
- 2004-06-17 US US10/870,268 patent/US7718666B2/en not_active Expired - Fee Related
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- 2005-12-01 IL IL172330A patent/IL172330A/en not_active IP Right Cessation
- 2005-12-15 CO CO05126707A patent/CO5640136A2/es not_active Application Discontinuation
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| IL172330A (en) | 2011-02-28 |
| TW200504063A (en) | 2005-02-01 |
| DE602004022294D1 (en) | 2009-09-10 |
| US20040259902A1 (en) | 2004-12-23 |
| JP2007526876A (ja) | 2007-09-20 |
| EP1638968B1 (en) | 2009-07-29 |
| BRPI0411509A (pt) | 2006-07-25 |
| KR100744893B1 (ko) | 2007-08-01 |
| JP4445504B2 (ja) | 2010-04-07 |
| NO20055680L (no) | 2006-01-11 |
| NZ543863A (en) | 2009-05-31 |
| KR20060026431A (ko) | 2006-03-23 |
| AU2004251829B2 (en) | 2009-12-17 |
| RU2339636C2 (ru) | 2008-11-27 |
| US7718666B2 (en) | 2010-05-18 |
| MXPA05013734A (es) | 2006-03-08 |
| RU2006101457A (ru) | 2007-07-27 |
| CA2528784C (en) | 2012-02-21 |
| NO20055680D0 (no) | 2005-12-01 |
| CO5640136A2 (es) | 2006-05-31 |
| CN101090901A (zh) | 2007-12-19 |
| ATE437876T1 (de) | 2009-08-15 |
| AU2004251829A1 (en) | 2005-01-06 |
| AR044796A1 (es) | 2005-10-05 |
| ES2327740T3 (es) | 2009-11-03 |
| CA2528784A1 (en) | 2005-01-06 |
| WO2005000846A1 (en) | 2005-01-06 |
| CN101090901B (zh) | 2010-12-15 |
| EP1638968A1 (en) | 2006-03-29 |
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