EP0651642A1 - Utilisation de 1,3-dicyclopropymethyl-8-amino-xanthine pour le traitement et la prevention du diabete sucre de type ii et de l'obesite - Google Patents

Utilisation de 1,3-dicyclopropymethyl-8-amino-xanthine pour le traitement et la prevention du diabete sucre de type ii et de l'obesite

Info

Publication number
EP0651642A1
EP0651642A1 EP93917883A EP93917883A EP0651642A1 EP 0651642 A1 EP0651642 A1 EP 0651642A1 EP 93917883 A EP93917883 A EP 93917883A EP 93917883 A EP93917883 A EP 93917883A EP 0651642 A1 EP0651642 A1 EP 0651642A1
Authority
EP
European Patent Office
Prior art keywords
treatment
compound
obesity
day
type
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP93917883A
Other languages
German (de)
English (en)
Inventor
Barbara Anne Smithkline Beecham Pharm. Spicer
Kathryn Gay Smithkline Beecham Pharm. Ellis
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Publication of EP0651642A1 publication Critical patent/EP0651642A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • 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
    • 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

Definitions

  • the present invention relates to a method for the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes and a compound for use in such method.
  • R* and R ⁇ each independendy represent alkyl or a moiety of formula (a):
  • A represents a substituted or unsubstituted cyclic hydrocarbon radical, providing that when R- represents methyl then R is not methyl;
  • R3a represents a halogen atom, a nitro group, or a group -NR4R5 wherein R4 and R ⁇ each independently represent hydrogen, alkyl or alkylcarbonyl or R ⁇ and R5 together with the nitrogen to which they are attached form an optionally substituted heterocyclic group.
  • Example 9 of EP 903030930.0 is 1,3-di-cyclopropymethyl- 8-amino xanthine (hereinafter preferred to as Compound 1).
  • the compounds in European application No. 90303093.0 are described inter alia as having activity in the treatment of cerebral vascular and neuronal degenerative disease and to act as phosphodiesterase inhibitors elevating cyclic AMP levels.
  • Compound 1 increases energy expenditure and also decreases food intake and is therefore of potential use in the treatment of obesity in mammals, including humans.
  • Compound I is also indicated to be effective in improving insulin sensitivity and hence to be effective in the treatment of Type II diabetes.
  • the present invention provides a method for the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes in mammals, such as humans, which comprises administering to the mammal in need of such treatment and/or prophylaxis an effective and/or prophylactic, non-toxic amount of Compound 1.
  • the present invention also provides Compound 1 for use in the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes.
  • a pharmaceutical composition for use in the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes which comprises Compound 1 and a pharmaceutically acceptable carrier.
  • the present invention provides the use of Compound 1 for the manufacture of a medicament for the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes.
  • the administration to the mammal may be by way of oral administration or parenteral administration.
  • a unit dose will normally contain 0.1 to 200 mg for example 5 to 50 mg or 1 to 20 mg, of Compound 1.
  • Unit doses will normally be administered once or more than once a day, for example 1, 2, 3, 4, 5 or 6 times a day, more usually 1 to 4 times a day, such that the total daily dose is normally in the range, for a 70 kg adult of 0.5 to 500 mg, for example 50 to 250 mg or 10 to 150 mg, that is in the range of approximately 0.001 to 10 mg kg day, more usually 1 to 3 mg/kg day or 0.2 to 2.5 mg/kg/day, for example 0.7 to 2 mg/kg/day.
  • Compound 1 is administered in the form of a unit-dose composition, such as a unit dose oral or parenteral composition.
  • a unit dose composition such as a unit dose oral or parenteral composition.
  • Such compositions are prepared by admixture and are suitably adapted for oral or parenteral administration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable and infusable solutions or suspensions.
  • Orally administrable compositions are preferred, in particular shaped oral compositions, since they are more convenient for general use.
  • Tablets and capsules for oral administration are usually presented in a unit dose, and contain conventional excipients such as binding agents, fillers, diluents, tabletting agents, lubricants, disintegrants, colourants, flavourings, and wetting agents.
  • the tablets may be coated according to well known methods in the art.
  • Suitable fillers for use include cellulose, mannitol, lactose and other similar agents.
  • Suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycollate.
  • Suitable lubricants include, for example, magnesium stearate.
  • Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
  • solid oral compositions may be prepared by conventional methods of blending, filling, tabletting or the like. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are, of course, conventional in the art.
  • Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils), for example, almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl j>-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
  • suspending agents for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monoole
  • Oral formulations also include conventional sustained release formulations, such as tablets or granules having an enteric coating.
  • fluid unit dose forms are prepared containing Compound 1 and a sterile vehicle.
  • the compound depending on the vehicle and the concentration, can be either suspended or dissolved.
  • Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and the water removed under vacuum.
  • Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound.
  • test animals were 12 male and 12 female, Sprague-Dawley rats (body weights 200-270g, approximately 8-10 weeks of age).
  • the rats were fed on SQC rat and mouse maintenance diet No. 1; diet and drinking water were freely available.
  • test compound was administered orally to the treatment group by oesophageal gavage as a suspension in 1% aqueous methylcellulose at a dose level of 1 mg/kg/day. Animals were dosed at a constant dose volume of lml/lOOg of bodyweight.
  • mice Female CFLP mice (29-37g) were fed ad libitium on a pelleted diet and housed in pairs on a light cycle in which lights were off from 6pm to 6am. Compound 1 or vehicle was given at 2pm and food intake and body weight changes were measured over the following 20 hours. Results are means ⁇ SEM of 5 (food intake) or 10 (body weight) values.

Landscapes

  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Procédé de traitement et/ou de prophylaxie de l'obésité ou pour le traitement du diabète de type II chez les mammifères, tels que les humains, ce procédé consistant à administrer au mammifère nécessitant un tel traitement et/ou une telle prophylaxie une dose efficace et/ou prophylactique, non toxique du composé 1 (1,3-dicyclopropyméthyl-8-amino-xanthine).
EP93917883A 1992-07-23 1993-07-21 Utilisation de 1,3-dicyclopropymethyl-8-amino-xanthine pour le traitement et la prevention du diabete sucre de type ii et de l'obesite Withdrawn EP0651642A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB929215633A GB9215633D0 (en) 1992-07-23 1992-07-23 Novel treatment
GB9215633 1992-07-23
PCT/GB1993/001539 WO1994002150A1 (fr) 1992-07-23 1993-07-21 Utilisation de 1,3-dicyclopropymethyl-8-amino-xanthine pour le traitement et la prevention du diabete sucre de type ii et de l'obesite

Publications (1)

Publication Number Publication Date
EP0651642A1 true EP0651642A1 (fr) 1995-05-10

Family

ID=10719151

Family Applications (1)

Application Number Title Priority Date Filing Date
EP93917883A Withdrawn EP0651642A1 (fr) 1992-07-23 1993-07-21 Utilisation de 1,3-dicyclopropymethyl-8-amino-xanthine pour le traitement et la prevention du diabete sucre de type ii et de l'obesite

Country Status (9)

Country Link
EP (1) EP0651642A1 (fr)
JP (1) JPH07509456A (fr)
CN (1) CN1043610C (fr)
AU (1) AU4714393A (fr)
GB (1) GB9215633D0 (fr)
MX (1) MX9304435A (fr)
TW (1) TW258663B (fr)
WO (1) WO1994002150A1 (fr)
ZA (1) ZA935339B (fr)

Families Citing this family (33)

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Publication number Priority date Publication date Assignee Title
US5783408A (en) * 1995-06-07 1998-07-21 Hamilton; Bradford S. Method for screening potential anti-obesity agents
RS50955B (sr) * 2001-02-24 2010-08-31 Boehringer Ingelheim Pharma Gmbh. & Co.Kg. Derivati ksantina, njihovo dobijanje i njihova primena kao lekova
WO2003004496A1 (fr) * 2001-07-03 2003-01-16 Novo Nordisk A/S Derives de purine inhibiteurs de dpp-iv pour le traitement du diabete
US6869947B2 (en) 2001-07-03 2005-03-22 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme DPP-IV
JP2005509603A (ja) * 2001-09-19 2005-04-14 ノボ　ノルディスク　アクティーゼルスカブ Ｄｐｐ−ｉｖ酵素の阻害剤であるヘテロ環化合物
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
DE10254304A1 (de) * 2002-11-21 2004-06-03 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel
MXPA06002521A (es) 2003-09-05 2006-06-20 Altana Pharma Ag Uso de inhibidores de pde4 para el tratamiento de diabetes mellitus.
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
DE102004030502A1 (de) 2004-06-24 2006-01-12 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel
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
NZ560269A (en) 2005-03-08 2010-12-24 Nycomed Gmbh Roflumilast for the treatment of diabetes mellitus
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
EP1852108A1 (fr) 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG Compositions d'inhibiteurs de la DPP IV
PE20110235A1 (es) 2006-05-04 2011-04-14 Boehringer Ingelheim Int Combinaciones farmaceuticas que comprenden linagliptina y metmorfina
NZ619413A (en) 2006-05-04 2015-08-28 Boehringer Ingelheim Int Polymorphs of a dpp-iv enzyme inhibitor
AR071175A1 (es) 2008-04-03 2010-06-02 Boehringer Ingelheim Int Composicion farmaceutica que comprende un inhibidor de la dipeptidil-peptidasa-4 (dpp4) y un farmaco acompanante
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"
BRPI0919288A2 (pt) 2008-09-10 2015-12-15 Boehring Ingelheim Internat Gmbh teriapia de combinação para tratamento de diabetes e condições relacionadas.
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
CN102256976A (zh) 2008-12-23 2011-11-23 贝林格尔.英格海姆国际有限公司 有机化合物的盐形式
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
KR20210033559A (ko) 2009-11-27 2021-03-26 베링거 인겔하임 인터내셔날 게엠베하 리나글립틴과 같은 ｄｐｐ－ｉｖ 억제제를 사용한 유전자형 검사된 당뇨병 환자의 치료
CN102946875A (zh) 2010-05-05 2013-02-27 贝林格尔.英格海姆国际有限公司 组合疗法
EP3124041A1 (fr) 2010-06-24 2017-02-01 Boehringer Ingelheim International GmbH Traitement du diabète
AR083878A1 (es) 2010-11-15 2013-03-27 Boehringer Ingelheim Int Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento
AU2012285904C1 (en) 2011-07-15 2017-08-31 Boehringer Ingelheim International Gmbh Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
EP2849755A1 (fr) 2012-05-14 2015-03-25 Boehringer Ingelheim International GmbH Dérivé de xanthine en tant qu'inhibiteur de dpp-4 pour l'utilisation dans le traitement de troubles associés aux podocytes et/ou un syndrome néphrotique
WO2013174767A1 (fr) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh Dérivé de xanthine en tant qu'inhibiteur de la dpp-4 à utiliser dans la modification de l'apport alimentaire et dans la régulation des préférences alimentaires
US9526728B2 (en) 2014-02-28 2016-12-27 Boehringer Ingelheim International Gmbh Medical use of a DPP-4 inhibitor
WO2017211979A1 (fr) 2016-06-10 2017-12-14 Boehringer Ingelheim International Gmbh Combinaisons de linagliptine et de metformine

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GB8906792D0 (en) * 1989-03-23 1989-05-10 Beecham Wuelfing Gmbh & Co Kg Treatment and compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9402150A1 *

Also Published As

Publication number Publication date
GB9215633D0 (en) 1992-09-09
JPH07509456A (ja) 1995-10-19
ZA935339B (en) 1995-01-18
CN1043610C (zh) 1999-06-16
CN1114880A (zh) 1996-01-17
AU4714393A (en) 1994-02-14
WO1994002150A1 (fr) 1994-02-03
TW258663B (fr) 1995-10-01
MX9304435A (es) 1994-04-29

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