AU2012254158B2 - Compounds and methods of treating diabetes - Google Patents

Compounds and methods of treating diabetes Download PDF

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Publication number
AU2012254158B2
AU2012254158B2 AU2012254158A AU2012254158A AU2012254158B2 AU 2012254158 B2 AU2012254158 B2 AU 2012254158B2 AU 2012254158 A AU2012254158 A AU 2012254158A AU 2012254158 A AU2012254158 A AU 2012254158A AU 2012254158 B2 AU2012254158 B2 AU 2012254158B2
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Australia
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AU2012254158A1 (en
Inventor
Sarvajit Chakravarty
Michael John Green
Rajendra Parasmal Jain
Andrew Asher Protter
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Medivation Technologies LLC
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Medivation Technologies LLC
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/12Drugs for disorders of the metabolism for electrolyte homeostasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/48Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10Antioedematous agents; Diuretics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/06Antiarrhythmics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D451/00Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D455/00Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C07D455/03Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/12Heterocyclic 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 three hetero rings
    • C07D471/14Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/12Heterocyclic 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 three hetero rings
    • C07D471/18Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/22Heterocyclic 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 systems contains four or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Emergency Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Child & Adolescent Psychology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
AU2012254158A 2011-02-18 2012-02-17 Compounds and methods of treating diabetes Ceased AU2012254158B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2013203871A AU2013203871A1 (en) 2011-02-18 2012-02-17 Compounds and methods of treating diabetes

Applications Claiming Priority (17)

Application Number Priority Date Filing Date Title
US201161444642P 2011-02-18 2011-02-18
US201161444655P 2011-02-18 2011-02-18
US201161444659P 2011-02-18 2011-02-18
US61/444,642 2011-02-18
US61/444,659 2011-02-18
US61/444,655 2011-02-18
US201161469664P 2011-03-30 2011-03-30
US61/469,664 2011-03-30
US201161529745P 2011-08-31 2011-08-31
US201161529816P 2011-08-31 2011-08-31
US61/529,816 2011-08-31
US61/529,745 2011-08-31
US201161562927P 2011-11-22 2011-11-22
US201161562938P 2011-11-22 2011-11-22
US61/562,927 2011-11-22
US61/562,938 2011-11-22
PCT/US2012/025749 WO2012154261A1 (en) 2011-02-18 2012-02-17 Compounds and methods of treating diabetes

Related Child Applications (1)

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AU2013203871A Division AU2013203871A1 (en) 2011-02-18 2012-02-17 Compounds and methods of treating diabetes

Publications (2)

Publication Number Publication Date
AU2012254158A1 AU2012254158A1 (en) 2013-05-02
AU2012254158B2 true AU2012254158B2 (en) 2016-02-04

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AU2012254158A Ceased AU2012254158B2 (en) 2011-02-18 2012-02-17 Compounds and methods of treating diabetes
AU2012219251A Ceased AU2012219251B2 (en) 2011-02-18 2012-02-17 Compounds and methods for treatment of hypertension

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US (5) US8815843B2 (show.php)
EP (2) EP2675458A4 (show.php)
JP (2) JP2014505738A (show.php)
CN (2) CN103476417A (show.php)
AU (2) AU2012254158B2 (show.php)
BR (2) BR112013021125A2 (show.php)
CA (2) CA2827642A1 (show.php)
IN (1) IN2013MN01699A (show.php)
WO (2) WO2012154261A1 (show.php)

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6302875B1 (en) 1996-10-11 2001-10-16 Transvascular, Inc. Catheters and related devices for forming passageways between blood vessels or other anatomical structures
US9636174B2 (en) 2002-04-08 2017-05-02 Medtronic Ardian Luxembourg S.A.R.L. Methods for therapeutic renal neuromodulation
US20070135875A1 (en) 2002-04-08 2007-06-14 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US7653438B2 (en) 2002-04-08 2010-01-26 Ardian, Inc. Methods and apparatus for renal neuromodulation
US20070129761A1 (en) 2002-04-08 2007-06-07 Ardian, Inc. Methods for treating heart arrhythmia
US20080213331A1 (en) 2002-04-08 2008-09-04 Ardian, Inc. Methods and devices for renal nerve blocking
US8150519B2 (en) 2002-04-08 2012-04-03 Ardian, Inc. Methods and apparatus for bilateral renal neuromodulation
US7617005B2 (en) 2002-04-08 2009-11-10 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US7803168B2 (en) 2004-12-09 2010-09-28 The Foundry, Llc Aortic valve repair
RU2007139634A (ru) 2007-10-25 2009-04-27 Сергей Олегович Бачурин (RU) Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения
RU2544856C2 (ru) * 2008-01-25 2015-03-20 Сергей Олегович Бачурин НОВЫЕ ПРОИЗВОДНЫЕ 2,3,4,5-ТЕТРАГИДРО-1-ПИРИДО[4,3-b]ИНДОЛА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
TWI450900B (zh) 2008-03-24 2014-09-01 Medivation Technologies Inc 橋聯雜環化合物及使用方法
US8338447B2 (en) 2008-03-24 2012-12-25 Medivation Technologies, Inc. Pyrido[3,4-B]indoles and methods of use
US8569287B2 (en) 2008-10-31 2013-10-29 Medivation Technologies, Inc. Azepino[4,5-B]indoles and methods of use
CN102271508B (zh) * 2008-10-31 2015-04-29 梅迪维新技术公司 含有刚性部分的吡啶并[4,3-b]吲哚类化合物
EP2424364A4 (en) 2009-04-29 2012-12-19 Medivation Technologies Inc PYRIDO [4.3-B] INDOLES AND METHODS OF USE
WO2011019417A1 (en) 2009-04-29 2011-02-17 Medivation Technologies, Inc. Pyrido [4, 3-b] indoles and methods of use
US9079904B2 (en) * 2009-09-23 2015-07-14 Medivation Technologies, Inc. Pyrido[3,4-B]indoles and methods of use
US8859561B2 (en) 2009-09-23 2014-10-14 Medivation Technologies, Inc. Pyrido[4,3-b]indoles and methods of use
BR112012006648A2 (pt) 2009-09-23 2019-09-24 Medivation Neurology Inc composto,método de tratamento de um distúrbio cognitivo, distúrbio psicótico, distúrbio mediado por neurotransmissor ou um distúrbio neuronal, composição farmacêutica e kit
US9040519B2 (en) 2010-02-18 2015-05-26 Medivation Technologies, Inc. Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use
US9034865B2 (en) 2010-02-18 2015-05-19 Medivation Technologies, Inc. Pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use
US9193728B2 (en) 2010-02-18 2015-11-24 Medivation Technologies, Inc. Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use
US9187471B2 (en) 2010-02-19 2015-11-17 Medivation Technologies, Inc. Pyrido [4,3-b] indole and pyrido [3,4-b] indole derivatives and methods of use
IN2013MN01699A (show.php) 2011-02-18 2015-06-12 Medivation Technologies Inc
WO2012112964A2 (en) 2011-02-18 2012-08-23 Medivation Technologies, Inc. PYRIDO[4,3-b]INDOLE AND PYRIDO[3,4-b]INDOLE DERIVATIVES AND METHODS OF USE
US9199985B2 (en) 2011-02-18 2015-12-01 Medivation Technologies, Inc. Compounds and methods for treatment of hypertension
WO2012112965A1 (en) 2011-02-18 2012-08-23 Medivation Technologies, Inc. Compounds and methods of treating diabetes
CN103517731B (zh) 2011-04-08 2016-08-31 柯惠有限合伙公司 用于去除肾交感神经和离子电渗式药物传递的离子电渗式药物传递系统和方法
JP5958772B2 (ja) * 2011-11-18 2016-08-02 時人 雪村 腎障害の治療又は予防薬
US20150315188A1 (en) * 2012-08-22 2015-11-05 Medivation Technologies, Inc. Compounds and methods for treatment of hypertension
MX2016006688A (es) * 2013-11-22 2016-11-29 Pharmakea Inc Inhibidores tetraciclicos de autotaxina.
WO2015077503A1 (en) 2013-11-22 2015-05-28 Pharmakea, Inc. Autotaxin inhibitor compounds
IL280863B2 (en) 2015-05-27 2024-07-01 Sabre Therapeutics Llc Autotaxin inhibitors and uses thereof
EP3519816A4 (en) 2016-09-29 2020-05-06 The Regents of the University of California Compounds for increasing neural plasticity
US11116561B2 (en) 2018-01-24 2021-09-14 Medtronic Ardian Luxembourg S.A.R.L. Devices, agents, and associated methods for selective modulation of renal nerves
CN113784962B (zh) 2019-02-27 2025-04-25 加利福尼亚大学董事会 用于治疗脑部疾病的氮杂环庚三烯并-吲哚类和其他杂环
WO2022225839A1 (en) * 2021-04-20 2022-10-27 Bacainn Therapeutics, Inc. Cyclosporine compositions and methods of use
JP2025502615A (ja) 2021-12-15 2025-01-28 デリックス セラピューティクス,インク. フェノキシおよびベンジルオキシ置換サイコプラストゲンならびにその使用
KR20230171634A (ko) * 2022-06-14 2023-12-21 주식회사 레고켐 바이오사이언스 엑토뉴클레오티드 피로포스파타아제 포스포디에스터라아제-1 저해 화합물 및 이를 함유하는 약제학적 조성물

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3484449A (en) * 1966-05-12 1969-12-16 Hoffmann La Roche Certain substituted phenyl amino-ethylpyridine intermediates
WO2009005771A1 (en) * 2007-06-28 2009-01-08 Medivation Neurology, Inc. A drug demonstrating anxiolytic effect based on hydrogenated pyrido (4, 3-b) indoles, its pharmacological compound and application method
EP2145887A2 (en) * 2007-04-05 2010-01-20 Alla Chem, LLC. Substituted 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indoles, methods for the production and use thereof
WO2010051501A1 (en) * 2008-10-31 2010-05-06 Medivation Technologies, Inc. Pyrido (4,3-b) indoles containing rigid moieties
US20100125085A1 (en) * 2008-11-17 2010-05-20 Auspex Pharmaceuticals, Inc. Pyridoindole modulators of nmda receptor and acetylcholinesterase
US20100152163A1 (en) * 2008-10-31 2010-06-17 Hung David T Azepino[4,5-b]indoles and methods of use
US20100173824A1 (en) * 2002-05-24 2010-07-08 Exelixis, Inc. Azepinoindole Derivatives As Pharmaceutical Agents
WO2011103448A1 (en) * 2010-02-19 2011-08-25 Medivation Technologies, Inc. Methods and compositions for treating psychotic disorders using antipsychotic combination therapy

Family Cites Families (99)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2642438A (en) 1949-07-15 1953-06-16 Hoffmann La Roche Pyridindoles and method of manufacture
GB721171A (en) 1951-04-30 1954-12-29 Bayer Ag Derivatives of ª‰- and ª†- carbolines
CH445509A (de) 1964-12-03 1967-10-31 Geigy Ag J R Verfahren zur Herstellung von neuen Indolderivaten
US3409628A (en) 1966-05-12 1968-11-05 Hoffmann La Roche 5-(3-pyridylethyl)pyridoindole derivatives
US3525750A (en) 1966-05-31 1970-08-25 Geigy Chem Corp 1,2,3,4,5,6-hexahydro-azepino(4,5-b) indole derivatives
US3646045A (en) 1968-09-10 1972-02-29 Hoffmann La Roche Intermediates for 5-(4-pyridylethyl)-pyridoindole derivatives
US3502688A (en) 1968-09-10 1970-03-24 Hoffmann La Roche 5-(4-pyridylethyl)-pyridoindole derivatives
DK166478A (da) 1977-05-02 1978-11-03 Merck & Co Inc Fremgangsmaade til fremstilling af naphthyridiner
FR2516512A1 (fr) 1981-11-19 1983-05-20 Corbiere Jerome Nouveaux derives pyridoindoliques, leur procede de preparation et les compositions pharmaceutiques en contenant
JPS63163347A (ja) 1986-12-25 1988-07-06 Konica Corp 有機着色物質の光褪色防止方法
US4754038A (en) 1987-02-26 1988-06-28 American Home Products Corporation Carboline histamine H1 antagonists
US5360800A (en) 1987-09-03 1994-11-01 Glaxo Group Limited Tetrahydro-1H-pyrido[4,3-b]indol-1-one derivatives
ATE138659T1 (de) 1988-08-02 1996-06-15 Glaxo Group Ltd Lactamderivate
FR2663935A1 (fr) 1990-06-27 1992-01-03 Adir Nouveaux 1,2,3,4,5,6-hexahydroazepino [4,5-b] indoles et 1,2,3,4-tetrahydrobethacarbolines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent.
US5273977A (en) 1990-11-05 1993-12-28 Warner-Lambert Company Substituted tetrahydropyridines and hydroxypiperidines as central nervous system agents
US5250537A (en) 1992-03-13 1993-10-05 Scios Nova Inc. 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole,-6,7,8,9,10-hexahydro-7,11-imino-5H-cyclooct[b]indole and substituted derivatives
US5688807A (en) 1994-03-11 1997-11-18 Eli Lilly And Company Method for treating 5HT2B receptor related conditions
US5834482A (en) 1995-05-05 1998-11-10 Novo Nordisk A/S Heterocyclic chemistry
RU2140417C1 (ru) 1995-10-17 1999-10-27 Институт физиологически активных веществ РАН Производные гидрированных пиридо(4,3-b)индолов, способы их получения, фармацевтическая композиция и способ лечения
RU2106864C1 (ru) 1995-10-23 1998-03-20 Николай Серафимович Зефиров Средство для лечения болезни альцгеймера
TW470745B (en) 1996-05-23 2002-01-01 Janssen Pharmaceutica Nv Hexahydro-pyrido[4,3-b]indole derivatives
CA2310250A1 (en) 1997-11-14 1999-05-27 August Masaru Watanabe Treatment for alzheimer's disease
US6251893B1 (en) 1998-06-15 2001-06-26 Nps Allelix Corp. Bicyclic piperidine and piperazine compounds having 5-HT6 receptor affinity
FR2796644B1 (fr) 1999-07-23 2001-09-07 Adir Nouveaux derives de beta-carboline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP1254115A2 (en) * 2000-02-11 2002-11-06 Bristol-Myers Squibb Company Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators for treating respiratory and non-respiratory diseases
DE10030375A1 (de) 2000-06-21 2002-01-03 Bayer Ag Verwendung von MTP-Inhibitoren zur Senkung von ppTRL
JP2004509894A (ja) 2000-09-20 2004-04-02 ファルマシア・アンド・アップジョン・カンパニー 置換アゼピノ[4,5−b]インドリン誘導体
CA2453537A1 (en) 2001-08-08 2003-02-20 Pharmacia & Upjohn Company Therapeutic 1h-pyrido¬4,3-b|indoles
ATE356623T1 (de) 2002-01-18 2007-04-15 Aryx Therapeutics 5-ht3-rezeptorantagonisten und verwendungsverfahren
US7759336B2 (en) 2002-12-10 2010-07-20 Ono Pharmaceutical Co., Ltd. Nitrogen-containing heterocyclic compounds and medicinal use thereof
US7736889B2 (en) 2003-06-10 2010-06-15 The United States Of America As Represented By The Secretary Of The Navy Fluidic force discrimination
US20060293359A1 (en) 2003-06-25 2006-12-28 Allergan, Inc. Methods and compositions for the treatment of diabetes
US20070134733A1 (en) 2003-07-10 2007-06-14 Parallax Biosystems, Inc. Raman signature probes and their use in the detection and imaging of molecular processes and structures
US20050101623A1 (en) 2003-07-23 2005-05-12 Pharmacia Corporation Beta-carboline compounds and analogues thereof as mitogen-activated protein kinase-activated protein kinase-2 inhibitors
CA2532798C (en) 2003-07-23 2013-02-19 X-Ceptor Therapeutics Inc. Azepine derivatives as pharmaceutical agents
US20070179174A1 (en) 2003-12-08 2007-08-02 Bachurin Sergei O Methods and compositions for slowing aging
RU2283108C2 (ru) 2003-12-08 2006-09-10 Сергей Олегович Бачурин ГЕРОПРОТЕКТОР НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b) ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ
AP2334A (en) 2004-12-17 2011-12-06 Glenmark Pharmaceuticals Sa Novel heterocyclic compounds useful for the treatment of inflamatory and allergic disorders.
CN101175754A (zh) 2005-03-22 2008-05-07 阿斯利康(瑞典)有限公司 用作CB1受体配体的新四氢-1H-吡啶并[4,3-b]吲哚衍生物
EP1902044A1 (en) 2005-07-07 2008-03-26 Bio Medisinsk Innovasjon AS 5-htx modulators
AU2006275694A1 (en) 2005-07-28 2007-02-08 Bristol-Myers Squibb Company Substituted tetrahydro-1H-pyrido(4,3,b)indoles as serotonin receptor agonists and antagonists
CA2618087A1 (en) 2005-08-19 2007-03-01 Elan Pharmaceuticals, Inc. Bridged n-bicyclic sulfonamido inhibitors of gamma secretase
CA2624731A1 (en) 2005-10-04 2007-04-12 Medivation, Inc. Hydrogenated pyrido-indole compounds for the treatment of huntington's disease
RU2338537C2 (ru) 2006-01-25 2008-11-20 Сергей Олегович Бачурин СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ШИЗОФРЕНИИ НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b)ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ
AU2007297618A1 (en) 2006-09-20 2008-03-27 Medivation Neurology, Inc. Hydrogenated pyrido [4,3-b] indoles such as dimebon for treating canine Cognitive Dysfunction Syndrome
US20100099700A1 (en) 2006-09-20 2010-04-22 David Hung Hydrogenated pyrido (4,3-b) indoles for treating amyotrophic lateral sclerosis (als)
EP2420235A1 (en) 2006-10-27 2012-02-22 Medivation Neurology, Inc. Methods and combination therapies for treating alzheimer's disease
RU2329044C1 (ru) 2006-11-16 2008-07-20 Андрей Александрович Иващенко Лиганды 5-ht6 рецепторов, фармацевтическая композиция, способ ее получения и лекарственное средство
RU2334514C1 (ru) 2006-12-01 2008-09-27 Институт физиологически активных веществ Российской Академии наук СРЕДСТВО ДЛЯ УЛУЧШЕНИЯ КОГНИТИВНЫХ ФУНКЦИЙ И ПАМЯТИ НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО (4,3-b) ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ
RU2340342C2 (ru) 2006-12-07 2008-12-10 Сергей Олегович Бачурин СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ОСТРЫХ И ХРОНИЧЕСКИХ НАРУШЕНИЙ МОЗГОВОГО КРОВООБРАЩЕНИЯ, В ТОМ ЧИСЛЕ ИНСУЛЬТА, НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО[4,3-b]ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ
RU2338745C1 (ru) 2007-03-21 2008-11-20 Андрей Александрович Иващенко ЗАМЕЩЕННЫЕ 2,3,4,5-ТЕТРАГИДРО-1Н-ПИРИДО[4,3-b]ИНДОЛЫ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ
RU2339637C1 (ru) 2007-04-05 2008-11-27 Андрей Александрович Иващенко Блокаторы гистаминного рецептора для фармацевтических композиций, обладающих противоаллергическим и аутоиммунным действием
EP2150112A1 (en) 2007-04-26 2010-02-10 Merck & Co., Inc. 2-substituted indole derivatives as calcium channel blockers
BRPI0810942A2 (pt) 2007-05-25 2019-09-24 Medivation Neurology Inc método para tratar, previnir, retardar o início ou o desenvolvimento de uma condição, método para promover a diferenciação ou proliferação de uma célula, método para estimular o crescimento de neuritos ou para intensificar a neurogênese num indivíduo, método para auxiliar no tratamento de um indivíduo, método para diferenciar células-tronco multipotenciais, composição farmacêutica, e kit.
CN101687864A (zh) 2007-06-26 2010-03-31 阿斯利康(瑞典)有限公司 作为组织蛋白酶k抑制剂的1-氰基环丙基-衍生物
CA2719824A1 (en) 2007-08-01 2009-02-05 Medivation Neurology, Inc. Methods and compositions for treating schizophrenia using antipsychotic combination therapy
US20090221627A1 (en) 2007-09-20 2009-09-03 Alexey Aksinenko Fluoro-containing derivatives of hydrogenated pyrido[4,3-b]indoles with neuroprotective and cognition enhancing properties, process for preparing, and use
WO2009039420A1 (en) 2007-09-21 2009-03-26 Medivation Neurology, Inc. Methods and compositions for treating neuronal death mediated ocular diseases
RU2007139634A (ru) 2007-10-25 2009-04-27 Сергей Олегович Бачурин (RU) Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения
WO2009082268A2 (ru) 2007-12-21 2009-07-02 Alla Chem, Llc ЛИГАНДЫ α-АДРЕНОЦЕПТОРОВ, ДОПАМИНОВЫХ, ГИСТАМИНОВЫХ, ИМИДАЗОЛИНОВЫХ И СЕРОТОНИНОВЫХ РЕЦЕПТОРОВ И ИХ ПРИМЕНЕНИЕ
RU2544856C2 (ru) 2008-01-25 2015-03-20 Сергей Олегович Бачурин НОВЫЕ ПРОИЗВОДНЫЕ 2,3,4,5-ТЕТРАГИДРО-1-ПИРИДО[4,3-b]ИНДОЛА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
WO2009111540A1 (en) 2008-03-04 2009-09-11 Medivation Neurology, Inc. Methods for preparing pyridylethyl-substituted carbolines
HUE029767T2 (en) 2008-03-11 2017-04-28 Incyte Holdings Corp JAK inhibitor azetidine and cyclobutane derivatives
US8338447B2 (en) 2008-03-24 2012-12-25 Medivation Technologies, Inc. Pyrido[3,4-B]indoles and methods of use
TWI450900B (zh) 2008-03-24 2014-09-01 Medivation Technologies Inc 橋聯雜環化合物及使用方法
TWI450899B (zh) 2008-03-27 2014-09-01 被取代之螺環環已烷衍生物
WO2009135091A1 (en) 2008-04-30 2009-11-05 Medivation Technologies, Inc. Use of asenapine and related compounds for the treatment of neuronal or non-neuronal diseases or conditions
US20100080786A1 (en) 2008-05-20 2010-04-01 Markus Berger Phenyl or Pyridinyl Substituted Indazoles Derivatives
DE102008030206A1 (de) 2008-06-25 2009-12-31 Bayer Schering Pharma Aktiengesellschaft 3-Cyanoalky- und 3-Hydroxyalkyl-Indole und ihre Verwendung
WO2010014758A1 (en) 2008-07-30 2010-02-04 Edison Pharmaceuticals, Inc. Use of hydrogenated pyrido[4,3-b] indoles for the treatment of oxidative stress
US9625475B2 (en) 2008-09-29 2017-04-18 Abbvie Inc. Indole and indoline derivatives and methods of use thereof
PA8843701A1 (es) 2008-09-29 2010-05-26 Abbott Lab Derivados de indolina y métodos para usarlos
US20100130528A1 (en) * 2008-11-21 2010-05-27 Auspex Pharmaceuticals, Inc. Adamantane modulators of nmda receptor and/or 5ht3 receptor
CN102405043B (zh) 2009-01-09 2017-08-22 得克萨斯州大学系统董事会 前神经原性化合物
US9962368B2 (en) 2009-01-09 2018-05-08 Board Of Regents Of The University Of Texas System Pro-neurogenic compounds
US8362277B2 (en) 2009-01-09 2013-01-29 Board Of Regents Of The University Of Texas System Pro-neurogenic compounds
WO2011019417A1 (en) 2009-04-29 2011-02-17 Medivation Technologies, Inc. Pyrido [4, 3-b] indoles and methods of use
EP2424364A4 (en) 2009-04-29 2012-12-19 Medivation Technologies Inc PYRIDO [4.3-B] INDOLES AND METHODS OF USE
WO2011008312A2 (en) 2009-07-14 2011-01-20 Abbott Laboratories Indole and indoline derivatives and methods of use thereof
RU2009128817A (ru) 2009-07-28 2011-02-10 Общество с ограниченной ответственностью "Инномед" (RU) Производные гидрированных пиридо[4,3-b]индолов, фармацевтическая композиция, способы получения и применения
WO2011014695A1 (en) 2009-07-29 2011-02-03 Medivation Technologies, Inc. New 2,3,4,5-tetrahydro-1h-pyrido[4,3-b] indoles and methods of use
US8859561B2 (en) 2009-09-23 2014-10-14 Medivation Technologies, Inc. Pyrido[4,3-b]indoles and methods of use
US9079904B2 (en) 2009-09-23 2015-07-14 Medivation Technologies, Inc. Pyrido[3,4-B]indoles and methods of use
US20130137705A1 (en) 2009-09-23 2013-05-30 Sarvajit Chakravarty Pyrido[3,4-b]indoles and methods of use
BR112012006648A2 (pt) 2009-09-23 2019-09-24 Medivation Neurology Inc composto,método de tratamento de um distúrbio cognitivo, distúrbio psicótico, distúrbio mediado por neurotransmissor ou um distúrbio neuronal, composição farmacêutica e kit
US9040519B2 (en) 2010-02-18 2015-05-26 Medivation Technologies, Inc. Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use
US20130172320A1 (en) 2010-02-18 2013-07-04 Sarvajit Chakravarty Pyrido [4,3-b] indole and pyrido [3,4-b] indole derivatives and methods of use
US9193728B2 (en) 2010-02-18 2015-11-24 Medivation Technologies, Inc. Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use
US9034865B2 (en) 2010-02-18 2015-05-19 Medivation Technologies, Inc. Pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use
US9187471B2 (en) 2010-02-19 2015-11-17 Medivation Technologies, Inc. Pyrido [4,3-b] indole and pyrido [3,4-b] indole derivatives and methods of use
CA2804161A1 (en) 2010-07-07 2012-01-12 Board Of Regents Of The University Of Texas System Pro-neurogenic compounds
US8697700B2 (en) 2010-12-21 2014-04-15 Albany Molecular Research, Inc. Piperazinone-substituted tetrahydro-carboline MCH-1 antagonists, methods of making, and uses thereof
WO2012112964A2 (en) 2011-02-18 2012-08-23 Medivation Technologies, Inc. PYRIDO[4,3-b]INDOLE AND PYRIDO[3,4-b]INDOLE DERIVATIVES AND METHODS OF USE
WO2012112965A1 (en) 2011-02-18 2012-08-23 Medivation Technologies, Inc. Compounds and methods of treating diabetes
US9199985B2 (en) 2011-02-18 2015-12-01 Medivation Technologies, Inc. Compounds and methods for treatment of hypertension
IN2013MN01699A (show.php) 2011-02-18 2015-06-12 Medivation Technologies Inc
US20150315188A1 (en) 2012-08-22 2015-11-05 Medivation Technologies, Inc. Compounds and methods for treatment of hypertension
WO2014031170A1 (en) 2012-08-22 2014-02-27 Medivation Technologies, Inc. Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use
CA2882923A1 (en) 2012-08-24 2014-02-27 Board Of Regents Of The University Of Texas System Pro-neurogenic compounds

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3484449A (en) * 1966-05-12 1969-12-16 Hoffmann La Roche Certain substituted phenyl amino-ethylpyridine intermediates
US20100173824A1 (en) * 2002-05-24 2010-07-08 Exelixis, Inc. Azepinoindole Derivatives As Pharmaceutical Agents
EP2145887A2 (en) * 2007-04-05 2010-01-20 Alla Chem, LLC. Substituted 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indoles, methods for the production and use thereof
WO2009005771A1 (en) * 2007-06-28 2009-01-08 Medivation Neurology, Inc. A drug demonstrating anxiolytic effect based on hydrogenated pyrido (4, 3-b) indoles, its pharmacological compound and application method
WO2010051501A1 (en) * 2008-10-31 2010-05-06 Medivation Technologies, Inc. Pyrido (4,3-b) indoles containing rigid moieties
US20100152163A1 (en) * 2008-10-31 2010-06-17 Hung David T Azepino[4,5-b]indoles and methods of use
US20100125085A1 (en) * 2008-11-17 2010-05-20 Auspex Pharmaceuticals, Inc. Pyridoindole modulators of nmda receptor and acetylcholinesterase
WO2011103448A1 (en) * 2010-02-19 2011-08-25 Medivation Technologies, Inc. Methods and compositions for treating psychotic disorders using antipsychotic combination therapy

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