[go: up one dir, main page]

WO2009097416A1 - Imidazolylalkyl-pyridines utilisées comme inhibiteurs de la dbh - Google Patents

Imidazolylalkyl-pyridines utilisées comme inhibiteurs de la dbh Download PDF

Info

Publication number
WO2009097416A1
WO2009097416A1 PCT/US2009/032419 US2009032419W WO2009097416A1 WO 2009097416 A1 WO2009097416 A1 WO 2009097416A1 US 2009032419 W US2009032419 W US 2009032419W WO 2009097416 A1 WO2009097416 A1 WO 2009097416A1
Authority
WO
WIPO (PCT)
Prior art keywords
lower alkyl
hydrogen
compound
methyl
cns
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.)
Ceased
Application number
PCT/US2009/032419
Other languages
English (en)
Inventor
Christian Lavedan
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.)
Vanda Pharmaceuticals Inc
Original Assignee
Vanda Pharmaceuticals Inc
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 Vanda Pharmaceuticals Inc filed Critical Vanda Pharmaceuticals Inc
Publication of WO2009097416A1 publication Critical patent/WO2009097416A1/fr
Anticipated expiration legal-status Critical
Ceased 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
    • A61K31/435—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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • A61P5/08—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
    • 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

Definitions

  • DBH dopamine-beta-hydroxylase
  • Inhibitors of dopamine-beta-hydroxylase are reported to be useful for a variety of clinical purposes including but not limited to regulation of lipid metabolism, vasodilation, and treatment of hypertension, congestive heart failure, hyperthyroidism, Parkinson Disease, Post-Traumatic Stress Disorder, and Reward Deficiency Syndrom (RDS), and other diseases or conditions which are positively affected by increased dopamine and/or by decreased norepinephrine.
  • the present invention relates to the use of an imidazolyl pyridine, or a pharmaceutically acceptable salt thereof, as an inhibitor of dopamine-beta- hydroxylase (DBH) for treatment of CNS conditions and non-CNS conditions mediated in whole or in part by DBH activity.
  • DBH dopamine-beta- hydroxylase
  • Non-CNS conditions include, for example, for regulation of lipid metabolism, for vasodilation, and for treatment of hypertension, congestive heart failure, and hyperthyroidism.
  • CNS conditions include, for example, Post-Traumatic Stress Disorder, and Reward Deficiency Syndrom (RDS). More particularly, the present invention relates to use of compounds of formula (I),
  • Ri is hydrogen, lower alkyl, halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by lower alkyl
  • R 2 and R3 independently of one another are hydrogen or lower alkyl
  • R 4 is hydrogen, hydroxy, lower alkyl, lower alkoxy or halogen with an atomic number of 9 to 35, in free base or acid addition salt form
  • the bridge between the pyridine and the imidazole, illustrated as methylene is methylene or ethylene, to treat one or more of the following disorders: abnormal lipid regulation, hypertension, congestive heart failure, hyperthyroidism, cerebral arterial spasm (cerebral vasospasms), Post-Traumatic Stress Disorder, or Reward Deficiency Syndrome (RDS) as well, in general, as other conditions that can be positively affected by inhibition of DBH.
  • abnormal lipid regulation hypertension
  • congestive heart failure hyperthyroidism
  • cerebral arterial spasm Cerebral vasospasms
  • FIG. 1 shows DBH activity following treatment of human serum with Compound A at varied concentrations.
  • lower in the context of alkyl and alkoxy groups, denotes a radical having up to 7 carbon atoms, preferably up to 4 carbon atoms and more preferably up to 2 carbon atoms. Consequently, lower alkyl has especially up to 7 carbon atoms, preferably up to 4 carbon atoms, and in particular up to 2 carbon atoms and is, for example, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, or hexyl.
  • lower alkoxy has up to 7 carbon atoms, preferably up to 4 carbon atoms, and in particular up to 2 carbon atoms and is, for example, methoxy, ethoxy, propoxy, butoxy, tert- butoxy or hexyloxy.
  • lower alkyl or lower alkoxy groups present in the compounds of Formula (I) preferably have one or two carbon atoms and especially signify methyl or methoxy.
  • the imidazolylmethyl radical is preferably in position 2 of the pyridine.
  • Ri is preferably methyl or ethyl, more preferably methyl.
  • R 2 and R3 are preferably each hydrogen.
  • R 4 is preferably methyl, ethyl or hydrogen, more preferably methyl or hydrogen, and in particular hydrogen.
  • Ri is lower alkyl
  • R 2 and R 3 independently of one another are hydrogen or lower alkyl
  • R 4 is hydrogen, lower alkyl or halogen with an atomic number of 9 to 35.
  • Ri is methyl
  • R 2 and R 3 independently of one another are hydrogen or methyl
  • R 4 is hydrogen, methyl or halogen with an atomic number of 9 to 35.
  • Halogen with an atomic number of 9 to 35 denote in particular a fluorine and chlorine residue, more particularly a chlorine residue.
  • the preferred compound for use in the method of the invention is 2-(2- methylimidazol-1 -yl)methyl]pyhdine, hereinafter referred to as Compound A.
  • the compounds of Formula (I) may be present in free base form or in the form of their acid addition salts, including, for example, hydrogen fumarate and fumarate salt forms. Acid addition salts may be produced from the free bases in known manner, and vice versa.
  • the compounds of Formula (I) are known, e.g., from U.S. Patent Nos. 5,856,343 and 5,635,521 , which are incorporated herein by reference, or may be produced in accordance with known processes, i.e., analogously to known processes.
  • the compounds according to the invention are therefore useful to treat or prevent abnormal lipid metabolism, hypertension, congestive heart failure, and hyperthyroidism.
  • Abnormal lipid metabolism includes, for example, elevated plasma concentrations of one or more of cholesterol, triglycerides, very low density lipoproteins, and low density lipoproteins and low plasma concentrations of high density lipoproteins.
  • treatment refers to both prophylactic or preventive treatment as well as curative or disease-modifying treatment, including treatment of patients at risk of contracting the disease/disorder or suspected to have contracted the disease/disorder as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition.
  • Human serum is treated with Compound A at different concentrations (7 ⁇ M to 300 mM). (500-x) ⁇ l of serum and x ⁇ l of drug are combined. Two samples are made with just serum; one of which will serve as a baseline (serum and tyramine), and the other of which will serve as a blank (serum without tyramine). Samples are incubated at 37 0 C for 30 minutes.
  • 800 ⁇ l of the reaction mix (6 ml sodium acetate pH 5; 1.5 ml 0.2 M fumarate; 1.5 ml 0.2 M ascorbate; 1.5 ml 0.02 m pargyline; 4.5 ml 0.2 M NEM; 3.0 ml catalase; 6 ml H 2 O for 24 samples) is pipetted into plastic centrifuge tubes, and 50 ⁇ l of human serum and previously-included drug are added. 100 ⁇ l of tyramine is added (exclusive of the blank), and the centrifuge tubes are mixed in a vortex. Centrifuge tubes are incubated for 30 minutes at 37 0 C.
  • the reaction is stopped after 30 minutes by placing samples in ice, and adding 200 ⁇ l of 20% PCA, and vortexing. The tubes are then centrifuged for 20 minutes at 5,000 rpm, or 12K g for 5 minutes, to pellet the protein precipitate.
  • a 1 :1 suspension of AG50W-X4 and water is made (Biorad # 142-1351 ; 10 ml pack volume of AG50W-X4 and 10 ml of H 2 O; suspension can be stored at + 4°C).
  • 500 ⁇ l of suspension is added to a Microbio-spin column (Biorad #73266204), followed by centrifuge at 1000 g for 1 minute. The liquid is then discarded.
  • the international units are expressed per liter (iu/l), where one international unit represents one micromole of substrate (tyramine) converted to product (octopamine) per minute.
  • the loss of efficacy of Compound A at pH 7 may be explained by the limited solubility of Compound A at pH 7, due to partial protonation of only one of the two nitrogens (pKa's of Compound A are 4.92 and 7.79). Moreover, the activity of the DBH enzyme is optimal at pH 5, a range in which Compound A is perfectly in solution and protonated on both nitrogens.
  • the above example therefore supports use of Compound A and related structures, as described herein, in the treatment of disorders mediated by DBH activity.
  • the method of the invention pertains to treatment of non-CNS disorders, such as those listed above.
  • the method can also be used to treat CNS conditions mediated in whole or in part by DBH activity in the central nervous system, e.g., the brain.
  • CNS conditions include post-traumatic stress disorder (PTSD) and Reward Deficiency Syndrom (RDS), but do not include senile dementia, Alzheimer's Disease and further degenerative diseases characterized by cholinergic and noradrenergic lesions such as Huntington's chorea, Morbus Parkinson, Steei-Richardson syndrome, tardive dyskinesias, hyperkinesia, acute confusion disorders. Down's syndrome, myasthenia gravis and Friedrich's ataxia and depression.
  • PTSD post-traumatic stress disorder
  • RDS Reward Deficiency Syndrom
  • the compounds according to the invention may be administered by any conventional route, in particular enterally, orally, or topically, for example in the form of tablets, capsules or eye drops, or parenterally, for example in the form of injectable solutions or suspensions.
  • An effective amount of the active agent of the invention may be administered to a subject animal (typically a human but other animals, e.g., farm animals, pets and racing animals, can also be treated).
  • a subject animal typically a human but other animals, e.g., farm animals, pets and racing animals, can also be treated.
  • An effective amount is an amount that prevents, inhibits, or terminates symptoms of the particular condition being treated.
  • the appropriate dosage will, of course, vary depending upon, for example, the compound employed, the host, the mode of administration and the nature and severity of the condition being treated. However, in general, satisfactory results in animals are indicated to be obtained at daily dosages from about 0.05 to about 50 mg/kg animal body weight. In larger mammals, such as humans, an indicated daily dosage may typically range from about 0.1 mg to about 1600 mg, more typically about 1 mg to about 800 mg, and most typically about 10 mg to about 200 mg, conveniently administered, for example, in divided doses up to four times a day.
  • the amount of the compound actually administered will be determined by a physician, in the light of the relevant circumstances, including the condition to be treated, the choice of compound to be administered, the chosen route of administration, the age, weight, and response of the individual patient, and the severity of the patient's symptoms.
  • an imidazolylmethyl-pyridine will normally be administered as a pharmaceutical composition
  • a pharmaceutical composition comprising as the (or an) essential active ingredient at least one such compound in association with a solid or liquid pharmaceutically acceptable carrier and, optionally, with pharmaceutically acceptable adjuvants and excipients employing standard and conventional techniques.
  • the pharmaceutical compositions include suitable dosage forms for oral, parenteral (including subcutaneous, intramuscular, intradermal, intravenous, transdermal (such as via a dermal patch, gel, microneedle, iontophoresis, sonophoresis, or phonophoresis)), bronchial or nasal administration.
  • the preparation may be tableted, placed in a hard gelatin capsule in powder or pellet form, in the form of a troche or lozenge, or in a chewable format such as a chewing gum.
  • the solid carrier may contain conventional excipients such as binding agents, fillers, tableting lubricants, disintegrants, wetting agents and the like.
  • the tablet may, if desired, be film coated by conventional techniques.
  • a liquid carrier the preparation may be in the form of a syrup, emulsion, soft gelatin capsule, sterile vehicle for injection, an aqueous or non-aqueous liquid suspension, or may be a dry product for reconstitution with water or other suitable vehicle before use.
  • Liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, wetting agents, non-aqueous vehicle (including edible oils), preservatives, as well as flavoring and/or coloring agents.
  • a vehicle normally will comprise sterile water, at least in large part, although saline solutions, glucose solutions and the like may be utilized.
  • injectable suspensions also may be used, in which case conventional suspending agents may be employed.
  • Conventional preservatives, buffering agents and the like also may be added to parenteral dosage forms.
  • compositions are prepared by conventional techniques appropriate to the desired preparation containing appropriate amounts of the active ingredient, that is, the compound of Formula (I) according to the invention. See, for example, Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa., 17th edition, 1985.
  • the active ingredient(s) will usually be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier, which may be in the form of a capsule, sachet, paper, or other container.
  • a carrier which may be in the form of a capsule, sachet, paper, or other container.
  • the carrier serves as a diluent, it may be a solid, semi-solid, or liquid material which acts as a vehicle, excipient or medium for the active ingredient.
  • the composition can be in the form of tablets, pills, powders, lozenges, gum, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments containing for example up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders.
  • suitable carriers and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl- and propylhydroxybenzoates, talc, magnesium stearate and mineral oil.
  • the formulations can additionally include lubricating agents, wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents, or flavoring agents.
  • the compositions of the invention may be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient.
  • compositions are preferably formulated in a unit dosage form, each dosage containing from about 0.1 to 800 mg of the active ingredient.
  • unit dosage form refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with the required pharmaceutical carrier.
  • the compounds of the present invention can also be used in combination with other agents, especially agents also shown to be useful in treating addictive disorders, psychoactive substance use disorders, intoxication disorders, inhalation disorders, alcohol addiction, tobacco addiction and or nicotine addiction, by substitution for a more harmful substance.

Landscapes

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

Abstract

L'invention concerne une méthode de régulation du métabolisme lipidique, de la vasodilation, et une méthode de traitement de l'hypertension, de l'insuffisance cardiaque congestive, de l'hyperthyroïdie et d'autres maladies ou états liés ou non au système nerveux central, y compris les troubles de stress post-traumatique et le trait hypodopaminergique (RDS), sur lesquels l'inhibition de la DBH et/ou l'accroissement de la dopamine et/ou la diminution de la noradrénaline influent positivement.
PCT/US2009/032419 2008-01-29 2009-01-29 Imidazolylalkyl-pyridines utilisées comme inhibiteurs de la dbh Ceased WO2009097416A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2426608P 2008-01-29 2008-01-29
US61/024,266 2008-01-29

Publications (1)

Publication Number Publication Date
WO2009097416A1 true WO2009097416A1 (fr) 2009-08-06

Family

ID=40419136

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/032419 Ceased WO2009097416A1 (fr) 2008-01-29 2009-01-29 Imidazolylalkyl-pyridines utilisées comme inhibiteurs de la dbh

Country Status (1)

Country Link
WO (1) WO2009097416A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012030953A1 (fr) 2010-09-01 2012-03-08 Arena Pharmaceuticals, Inc. Agonistes du récepteur 5-ht2c dans traitement de troubles améliorés par réduction du taux de noradrénaline
US8999970B2 (en) 2010-09-01 2015-04-07 Arena Pharmaceuticals, Inc. Administration of an anti-obesity compound to individuals with renal impairment
US9169213B2 (en) 2012-10-09 2015-10-27 Arena Pharmaceuticals, Inc. Method of weight management
US9248133B2 (en) 2010-09-01 2016-02-02 Arena Pharmaceuticals, Inc. Salts of lorcaserin with optically active acids
US9365521B2 (en) 2010-09-01 2016-06-14 Arena Pharmaceuticals, Inc. Non-hygroscopic salts of 5-HT2C agonists
US10226471B2 (en) 2010-09-01 2019-03-12 Arena Pharmaceuticals, Inc. Modified-release dosage forms of 5-HT2C agonists useful for weight management

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3701832A (en) * 1969-11-19 1972-10-31 Merck & Co Inc Method of inhibiting dopamine beta-hydroxylase
US4634711A (en) * 1985-08-02 1987-01-06 Smithkline Beckman Corporation Pyridylalkyl imidazole-2-thiols
EP0244803A2 (fr) * 1986-05-06 1987-11-11 Merrell Dow Pharmaceuticals Inc. Inhibiteurs de dopamine-bêta-hydroxylase
EP0302603A1 (fr) * 1987-07-09 1989-02-08 Smithkline Beecham Corporation Inhibiteurs de dopamine-bêta-hydroxylase
EP0534904A1 (fr) * 1991-09-23 1993-03-31 Sandoz Ltd. Imidazolylméthylpyridines
US5635521A (en) * 1991-09-23 1997-06-03 Sandoz Ltd. Imidazolylmethyl-pyridines
WO2001049871A2 (fr) * 2000-01-06 2001-07-12 Boehringer Ingelheim Pharma Kg Methode de recherche d'un inhibiteur de protease
WO2001081326A1 (fr) * 2000-04-21 2001-11-01 Suntory Limited 1-aza-2-imino-hétérocycles substitués et leur utilisation comme activateurs de récepteurs nicotiniques d'acétylcholine
WO2001081334A2 (fr) * 2000-04-21 2001-11-01 Suntory Limited Composes amidines cycliques
EP1176141A1 (fr) * 1999-03-05 2002-01-30 Suntory Limited COMPOSES HETEROCYCLIQUES POSSEDANT UN EFFET D'ACTIVATION DU RECEPTEUR $g(a)4$g(b)2 DE L'ACETYLCHOLINE NICOTINIQUE
US20040010015A1 (en) * 2000-07-07 2004-01-15 Wasimul Haque Pyridoxine and pyridoxal analogues: new uses

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3701832A (en) * 1969-11-19 1972-10-31 Merck & Co Inc Method of inhibiting dopamine beta-hydroxylase
US4634711A (en) * 1985-08-02 1987-01-06 Smithkline Beckman Corporation Pyridylalkyl imidazole-2-thiols
EP0244803A2 (fr) * 1986-05-06 1987-11-11 Merrell Dow Pharmaceuticals Inc. Inhibiteurs de dopamine-bêta-hydroxylase
EP0302603A1 (fr) * 1987-07-09 1989-02-08 Smithkline Beecham Corporation Inhibiteurs de dopamine-bêta-hydroxylase
EP0534904A1 (fr) * 1991-09-23 1993-03-31 Sandoz Ltd. Imidazolylméthylpyridines
US5635521A (en) * 1991-09-23 1997-06-03 Sandoz Ltd. Imidazolylmethyl-pyridines
EP1176141A1 (fr) * 1999-03-05 2002-01-30 Suntory Limited COMPOSES HETEROCYCLIQUES POSSEDANT UN EFFET D'ACTIVATION DU RECEPTEUR $g(a)4$g(b)2 DE L'ACETYLCHOLINE NICOTINIQUE
WO2001049871A2 (fr) * 2000-01-06 2001-07-12 Boehringer Ingelheim Pharma Kg Methode de recherche d'un inhibiteur de protease
WO2001081326A1 (fr) * 2000-04-21 2001-11-01 Suntory Limited 1-aza-2-imino-hétérocycles substitués et leur utilisation comme activateurs de récepteurs nicotiniques d'acétylcholine
WO2001081334A2 (fr) * 2000-04-21 2001-11-01 Suntory Limited Composes amidines cycliques
US20040010015A1 (en) * 2000-07-07 2004-01-15 Wasimul Haque Pyridoxine and pyridoxal analogues: new uses

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012030953A1 (fr) 2010-09-01 2012-03-08 Arena Pharmaceuticals, Inc. Agonistes du récepteur 5-ht2c dans traitement de troubles améliorés par réduction du taux de noradrénaline
US8999970B2 (en) 2010-09-01 2015-04-07 Arena Pharmaceuticals, Inc. Administration of an anti-obesity compound to individuals with renal impairment
US9248133B2 (en) 2010-09-01 2016-02-02 Arena Pharmaceuticals, Inc. Salts of lorcaserin with optically active acids
US9365521B2 (en) 2010-09-01 2016-06-14 Arena Pharmaceuticals, Inc. Non-hygroscopic salts of 5-HT2C agonists
US9770455B2 (en) 2010-09-01 2017-09-26 Arena Pharmaceuticals, Inc. Administration of an anti-obesity compound to individuals with renal impairment
US10226471B2 (en) 2010-09-01 2019-03-12 Arena Pharmaceuticals, Inc. Modified-release dosage forms of 5-HT2C agonists useful for weight management
US10463676B2 (en) 2010-09-01 2019-11-05 Arena Pharmaceuticals, Inc. Modified-release dosage forms of 5-HT2C agonists useful for weight management
US9169213B2 (en) 2012-10-09 2015-10-27 Arena Pharmaceuticals, Inc. Method of weight management

Similar Documents

Publication Publication Date Title
US12220414B2 (en) Use of sGC stimulators for the treatment of mitochondrial disorders
HUP0401097A2 (hu) Karbociklusos hidrazinovegyületek, mint a réztartalmú aminoxidázok inhibitorai, eljárás az előállításukra és ezeket tartalmazó gyógyszerkészítmények
WO2009097416A1 (fr) Imidazolylalkyl-pyridines utilisées comme inhibiteurs de la dbh
UA113759C2 (xx) Засоби для лікування порушень із залученням модуляції рецепторів ріанодіну
US12037350B2 (en) Compositions and methods for the prevention and/or treatment of mitochondrial disease, including Friedreich's ataxia
WO2014142290A1 (fr) Composé de pyrazole-amide et utilisations médicinales s'y rapportant
US20240368098A1 (en) Compositions and methods for the prevention and/or treatment of mitochondrial disease, including friedreich's ataxia
EP1446402B1 (fr) Derives de 2-amino-4-heteroarylethyl thiazoline et leur utilisation comme inhibiteurs de no-synthase inductible
RU2212237C2 (ru) Средство для лечения нейрогенного воспаления
US20170362237A1 (en) Water soluble salts of aldose reductase inhibitors for treatment of diabetic complications
JPH10139665A (ja) トログリタゾンを含有するグルタチオン還元酵素活性増強剤
CA2265656A1 (fr) Potentialisateur d'activite de glutathione-reductase contenant de la troglitazone
US20250302823A1 (en) Compositions and methods for treating hepatic porphyrias with glycine transport inhibitors
KR100759467B1 (ko) 차가버섯 또는 상황버섯으로부터 분리된 화합물을 함유하는통풍 예방 및 치료용 조성물
US11998532B1 (en) Substituted 1,3,4-oxadiazole derivatives as anti-tubercular agents
US20240336638A1 (en) Imidazole compound, and intermediate and application thereof
WO2019138995A1 (fr) Traitement de la sécheresse oculaire
WO2009085198A2 (fr) Combinaison de lipoate de metformine r-(+) et d'agents anti-obésité pour le traitement de l'hyperglycémie diabétique et des complications liées au diabète
JPH072867A (ja) ビオチンアミド誘導体の製造方法及び、それらを含有する糖尿病及び糖尿病合併症の治療剤
CA2604584C (fr) Composition pharmaceutique comprenant une 1-(3-chlorophenyl)-3-alkylpiperazine pour traiter les troubles de l'alimentation
EP4043442A1 (fr) Dérivés de 6-méthyluracile à activité anticholinestérasique et leur utilisation
JP2000086508A (ja) ヒスタミン遊離抑制剤
JPS62135426A (ja) 低酸素症改善剤
JPH09506068A (ja) 悪液質治療のためのオキソフタラジン類
JPH0753380A (ja) 高脂血症治療剤及び高尿酸血症治療剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09705656

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09705656

Country of ref document: EP

Kind code of ref document: A1