WO2001037780A2 - Urotensin-ii analogs - Google Patents
Urotensin-ii analogs Download PDFInfo
- Publication number
- WO2001037780A2 WO2001037780A2 PCT/US2000/032408 US0032408W WO0137780A2 WO 2001037780 A2 WO2001037780 A2 WO 2001037780A2 US 0032408 W US0032408 W US 0032408W WO 0137780 A2 WO0137780 A2 WO 0137780A2
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- cys
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- phe
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/57509—Corticotropin releasing factor [CRF] (Urotensin)
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- 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
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- 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
- A61P25/08—Antiepileptics; Anticonvulsants
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- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- 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
- A61P25/22—Anxiolytics
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- 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
- A61P25/24—Antidepressants
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- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
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- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
-
- 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
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
- A61P9/10—Drugs 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- the present invention relates generally Urotensin-II analogs and pharmaceutical compositions containing them.
- cardiovascular homeostasis The integrated control of cardiovascular homeostasis is achieved through a combination of both direct neuronal control and systemic neurohormonal activation. Although the resultant release of both contractile and relaxant factors is normally under stringent regulation, an aberration in this status quo can result in cardiohemodynamic dysfunction with pathological consequences.
- the principal mammalian vasoactive factors that comprise this neurohumoral axis namely angiotensin-II, endothelin-1, norepinephrine, all function via an interaction with specific G-protein coupled receptors (GPCR).
- GPCR G-protein coupled receptors
- this peptide has significant hemodynamic and endocrine actions in diverse end-organ systems and tissues:
- osmoregulation effects which include the modulation of transepithelial ion (Na + , Cl " ) transport. Although a diuretic effect has been described, such an effect is postulated to be secondary to direct renovascular effects (elevated GFR)
- Human Urotensin-II was assessed for contractile activity in the rat-isolated aorta and was shown to be the most potent contractile agonist identified to date. Based on the in vitro pharmacology and in vivo hemodynamic profile of human Urotensin-II it plays a pathological role in cardiovascular diseases characterized by excessive or abnormal vasoconstriction and myocardial dysfunction. (Ames et. al. Nature 1999, 401, 282)
- Urotensin-II analogs are useful for identifying agonists and antagonists/inhibitors of urotensin II, and for treating conditions associated with Human Urotensin II imbalance. For example, facilitating the actions of the U-II system, either by mimicking the agonist activity of U-II at its cognate receptor(s) or by attenuating the uptake/metabolism of U-II.
- These compounds may be useful in the treatment of congestive heart failure, stroke, ischemic heart disease (angina, myocardial ischemia), cardiac arrhythmia, hypertension (essential and pulmonary), COPD, restenosis, asthma, (Hay DWP, Luttmann MA, Douglas SA: 2000, Br J Pharmacol: volume 131 , pages 10-12) neurogenic inflammation and metabolic vasculopathies all of which are characterized by abnormal vasoconstriction and/or myocardial dysfunction. Since U-II and GPR14 are both expressed within the mammalian CNS (Ames et. al. Nature 1999, 401, 282), they also may be useful in the treatment of addiction, schizophrenia, impulsivity, anxiety, stress, depression, and neuromuscular function.
- U-II receptors are expressed in rhabdomyosarcomas cell lines and therefore may have oncological indications. Urotensin may also be implicated in various metabolic diseases such as diabetes (Ames et. al. Nature 1999, 401, 282, Nothacker et al., Nature Cell Biology 1 : 383-385, 1999).
- this invention provides for urotensin II analogs and pharmaceutical compositions containing them.
- this invention provides for the use of urotensin analogs for identifying agonists and antagonists of urotensin II, and as inhibitors of urotensin II. In another aspect, this invention provides for the use of urotensin analogs for treating conditions associated with urotensin II imbalance.
- this invention provides for the use of urotensin analogs for the treatment of congestive heart failure, stroke, ischemic heart disease (angina, myocardial ischemia), cardiac arrhythmia, hypertension (essential and pulmonary), COPD, restenosis, asthma, neurogenic inflammation and metabolic vasculopathies, addiction, schizophrenia, impulsivity, anxiety, stress, depression, neuromuscular function, and diabetes.
- the present invention provides for the following urotension II analogs and pharmaceutical compositions containing them : H-Glu-Thr-Pro-Asp-Cys-Phe-D-Trp-Lys-Tyr-Cys-Val-OH (cyclic disulfide); (SEQ ID NO: 1)
- H-Asp-Cys-Phe-D-Trp-Lys-Tyr-Cys-Val-OH (cyclic disulfide); (SEQ ID NO: 4) H-Asp-Cys-Cha-Trp-Lys-Cha-Cys-Val-OH (cyclic disulfide); (SEQ ID NO: 5) H-Asp-Cys-Phe-Trp-Lys-Cha-Cys-Val-OH (cyclic disulfide); (SEQ ID NO: 6) H-Asp-Cys-Phe-Trp-Lys-Phe-Cys-Val-OH (cyclic disulfide); (SEQ ID NO: 7) H-Asp-Cys-Cha-Trp-Lys-Tyr-Cys-Val-OH (cyclic disulfide); (SEQ ID NO: 8) H-Asp-Cys-Phe-Tr
- the compounds of the present invention may contain one or more asymmetric carbon atoms and may exist in racemic and optically active form. All of these compounds and their diastereoisomers are contemplated to be within the scope of the present invention.
- the resin was treated with 50% TFA in methylene chloride (two to three times resin volume), stirred at room temperature for 30 min and drained. The resin was washed once with an equal volume of isopropanol for 1 min, then washed twice with an equal volume of methanol for 1 min.
- Resin from (a) above was washed with an equal volume of 10% triethylamine in methylene chloride twice for 1 min, then washed with an equal volume of methanol twice for 1 min, and finally washed with an equal volume of methylene chloride twice for 1 min.
- To the resin was added three equivalents of terf-butoxycarbonyl amino acid (dissolved in methylene chloride or methylene chloride/N,N-dimethylformamide mixture), three equivalents of 1 -hydroxybenzotriazole hydrate (1 M solution in N,N-dimethylformamide) and the resultant suspension was stirred for one min.
- HPLC column Vydac C-18 RP silica, 15-20 uM, 2" diameter
- the crude peptides were loaded onto reverse phase HPLC column. A linear gradient was used over 30 min (100% water containing 0.1 % trifluoroacetic acid to 80% acetonitrile containing 0.1 % trifluoroacetic acid /20% water containing 0.1 % trifluoroacetic acid).
- Compounds of Formula (I) and their pharmaceutically acceptable salts may be administered in a standard manner for the treatment of the indicated diseases, for example orally, parenterally, sub-lingually, transdermally, rectally, via inhalation or via buccal administration.
- a syrup formulation will generally consist of a suspension or solution of the compound or salt in a liquid carrier for example, ethanol, peanut oil, olive oil, glycerin or water with a flavoring or coloring agent. Where the composition is in the form of a tablet, any pharmaceutical carrier routinely used for preparing solid formulations may be used.
- any pharmaceutical carrier routinely used for preparing dispersions or suspensions may be considered, for example aqueous gums, celluloses, silicates or oils and are inco ⁇ orated in a soft gelatin capsule shell.
- Typical parenteral compositions consist of a solution or suspension of the compound or salt in a sterile aqueous or non-aqueous carrier optionally containing a parenterally acceptable oil, for example polyethylene glycol, polyvinylpyrrolidone, lecithin, arachis oil, or sesame oil.
- Typical compositions for inhalation are in the form of a solution, suspension or emulsion that may be administered as a dry powder or in the form of an aerosol using a conventional propellant such as dichlorodifluoromethane or trichlorofluoromethane.
- a typical suppository formulation comprises a compound of Formula (1) or a pharmaceutically acceptable salt thereof which is active when administered in this way, with a binding and/or lubricating agent, for example polymeric glycols, gelatins, cocoa- butter or other low melting vegetable waxes or fats or their synthetic analogues.
- a binding and/or lubricating agent for example polymeric glycols, gelatins, cocoa- butter or other low melting vegetable waxes or fats or their synthetic analogues.
- Typical transdermal formulations comprise a conventional aqueous or non-aqueous vehicle, for example a cream, ointment, lotion or paste or are in the form of a medicated plaster, patch or membrane.
- a conventional aqueous or non-aqueous vehicle for example a cream, ointment, lotion or paste or are in the form of a medicated plaster, patch or membrane.
- the composition is in unit dosage form, for example a tablet, capsule or metered aerosol dose, so that the patients may administer to themselves a single dose.
- urotensin analogs may be used for the treatment of congestive heart failure, stroke, ischemic heart disease (angina, myocardial ischemia), cardiac arrhythmia, hypertension (essential and pulmonary), COPD, restenosis, asthma, neurogenic inflammation and metabolic vasculopathies, addiction, schizophrenia, impulsivity, anxiety, stress, depression, neuromuscular function, and diabetes.
- HEK-293 cell membranes containing stable cloned human and rat GPR-14 (20 ug/assay) were incubated with 200 pM [1251] h-U-II (200 Ci/mmol "1 in the presence of increasing concentrations of test compounds in DMSO (0.1 nM to 10 uM), in a final incubation volume of 200 ul (20 mM Tris-HCl, 5 mM MgC12). Incubation was done for 30 minutes at room temperature followed by filtration GF/B filters with Brandel cell harvester.
- ⁇ 2 ⁇ labeled U-II binding was quantitated by gamma counting. Nonspecific binding was defined by *25 ⁇ T J.JJ binding in the presence of 100 nM of unlabeled human U-II. Analysis of the data was performed by nonlinear least square fitting.
- a microtitre plate based Ca 2+ -mobilization FLIPR assay (Molecular Devices, Sunnyvale, CA) was used for the functional identification of the ligand activating HEK-293 cells expressing (stable) recombinant GPR-14.
- the day following transfection cells were plated in a poly-D-lysine coated 96 well black/clear plates. After 18-24 hours the media was aspirated and Fluo 3AM-loaded cells were exposed to various concentrations (10 nM to 30 uM) of test compounds followed by h-U-II. After initiation of the assay, fluorescence was read every second for one minute and then every 3 seconds for the following one minute. The inhibitory concentration at 50% (IC50) was calculated for various test compounds.
- HEK-293-GPR14 cells in T 150 flask were prelabeled overnight with 1 uCi myo- H] inositol per ml of inositol free Dulbecco's modified Eagel's medium. After labeling, the cells were washed twice with Dulbecco's phosphate-buffered saline (DPBS) and then incubated in DPBS containing 10 mM LiCl for 10 min at 37°C.
- DPBS Dulbecco's phosphate-buffered saline
- the experiment was initiated by the addition of increasing concentrations of h-U-II ( 1 pM to 1 ⁇ M ) in the absence and presence of three different concentrations (0.3, 1 and 10 uM) of test compounds and the incubation continued for an additional 5 min at 37°C after which the reaction was terminated by the addition of 10% (final concentration) trichloroacetic acid and centrifugation.
- the supernatants were neutralized with lOOul of 1M Trizma base and the inositol phosphates were separated on AG 1-X8 columns (0.8 ml packed, 100-200 mesh) in formate phase. Inositol monophosphate was eluted with 8 ml of 200 mM ammonium formate.
- Rats are surgically prepared with guide cannulae directed towards the lateral ventricle (verified by an intense drinking response to angiotensin II; lOOng i.e. v.). Following a two week recovery period, rats receive human urotensin-II, putative agonist ligand (1-10 ug, i.e. v.) or vehicle (0.9% saline solution) over min (allowing 90 sec for diffusion) in order to detect any neuroendocrine plasma changes.
- anesthetized rats are prepared for acute systemic exposure to human urotensin-II, putative agonist ligand (100 ug, bolus i.v.) or vehicle (0.9% saline solution) via an i.v. cannula placed in the left femoral of jugular vein.
- i.v. cannula placed in the left femoral of jugular vein.
- RIAs radioimmunoassays
- Neuroendocrine markers include but are not limited to:
- Pituitary hormones both anterior ⁇ e.g. ADH, OCT, ACTH) and posterior (e.g. GH, TSH,
- Thyroid/parathyroid hormones T4, T3, rT3, calcitonin, PTH
- Sex hormones including releasing hormones
- Vasoactive neurohormones ET, Angiotensin II, aldosterone, NE
- EXAMPLE 27 Formulations for pharmaceutical use inco ⁇ orating compounds of the present invention can be prepared in various forms and with numerous excipients. Examples of such formulations are given below.
- a compound of Formula I (1 mg to 100 mg) is aerosolized from a metered dose inhaler to deliver the desired amount of drug per use.
- Tablets/Ingredients Per Tablet 1. Active ingredient 40 mg (Cpd of Form. I) 2.Corn Starch 20 mg 3.Alginic acid 20 mg 4.Sodium Alginate 20 mg 5.Mg stearate 1.3 mg
- Step l Blend ingredients No. 1 , No. 2, No. 3 and No. 4 in a suitable mixer/blender.
- Step 2 Add sufficient water portion-wise to the blend from Step 1 with careful mixing after each addition. Such additions of water and mixing until the mass is of a consistency to permit its conversion to wet granules.
- Step 4 The wet granules are then dried in an oven at 140°F (60°C) until dry.
- Step 5 The dry granules are lubricated with ingredient No. 5.
- Step 6 The lubricated granules are compressed on a suitable tablet press.
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Addiction (AREA)
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Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001539397A JP2003527341A (en) | 1999-11-29 | 2000-11-29 | Urotensin-II analog |
EP00980842A EP1233774A4 (en) | 1999-11-29 | 2000-11-29 | Urotensin-ii analogs |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16814199P | 1999-11-29 | 1999-11-29 | |
US60/168,141 | 1999-11-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001037780A2 true WO2001037780A2 (en) | 2001-05-31 |
WO2001037780A8 WO2001037780A8 (en) | 2001-11-08 |
Family
ID=22610297
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/032408 WO2001037780A2 (en) | 1999-11-29 | 2000-11-29 | Urotensin-ii analogs |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP1233774A4 (en) |
JP (1) | JP2003527341A (en) |
WO (1) | WO2001037780A2 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004037863A1 (en) * | 2002-10-25 | 2004-05-06 | Takeda Pharmaceutical Company Limited | Antibody and utilization of the same |
WO2005023845A2 (en) | 2003-09-11 | 2005-03-17 | Ettore Novellino | Cyclic peptides acting as urotensin-ii antagonists |
US7241737B2 (en) * | 2000-10-20 | 2007-07-10 | Societe De Conseils De Recherches Et D'applications Scientifiques, Sas | Urotensin-II agonists and antagonists |
WO2008095995A2 (en) * | 2007-02-09 | 2008-08-14 | Ettore Novellino | Peptidic and non peptidic ligands for immunodetection of the receptor for urotensin ii |
WO2013068701A1 (en) * | 2011-11-10 | 2013-05-16 | Universite De Rouen | Urotensin-ii for use in the treatment and/or prevention of diseases involving gastric motility |
EP2729184A4 (en) * | 2011-05-03 | 2015-06-24 | Inst Nat Rech Scient | Novel agonists and antagonists of the urotensinergic system |
-
2000
- 2000-11-29 WO PCT/US2000/032408 patent/WO2001037780A2/en not_active Application Discontinuation
- 2000-11-29 JP JP2001539397A patent/JP2003527341A/en not_active Withdrawn
- 2000-11-29 EP EP00980842A patent/EP1233774A4/en not_active Withdrawn
Non-Patent Citations (1)
Title |
---|
See references of EP1233774A4 * |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7241737B2 (en) * | 2000-10-20 | 2007-07-10 | Societe De Conseils De Recherches Et D'applications Scientifiques, Sas | Urotensin-II agonists and antagonists |
WO2004037863A1 (en) * | 2002-10-25 | 2004-05-06 | Takeda Pharmaceutical Company Limited | Antibody and utilization of the same |
WO2005023845A2 (en) | 2003-09-11 | 2005-03-17 | Ettore Novellino | Cyclic peptides acting as urotensin-ii antagonists |
WO2008095995A2 (en) * | 2007-02-09 | 2008-08-14 | Ettore Novellino | Peptidic and non peptidic ligands for immunodetection of the receptor for urotensin ii |
WO2008095995A3 (en) * | 2007-02-09 | 2009-01-08 | Ettore Novellino | Peptidic and non peptidic ligands for immunodetection of the receptor for urotensin ii |
US20100099604A1 (en) * | 2007-02-09 | 2010-04-22 | Ettore Novellino | Peptidic and non peptidic ligands for immunodetection of the receptor for urotensin |
EP2592092A1 (en) | 2007-02-09 | 2013-05-15 | Ettore Novellino | Peptidic and non peptidic ligands for immunodetection of the receptor for urotensin II |
EP2729184A4 (en) * | 2011-05-03 | 2015-06-24 | Inst Nat Rech Scient | Novel agonists and antagonists of the urotensinergic system |
US9340575B2 (en) | 2011-05-03 | 2016-05-17 | Institut National De La Recherche Scientifique | Agonists and antagonists of the urotensinergic system |
WO2013068701A1 (en) * | 2011-11-10 | 2013-05-16 | Universite De Rouen | Urotensin-ii for use in the treatment and/or prevention of diseases involving gastric motility |
FR2982488A1 (en) * | 2011-11-10 | 2013-05-17 | Univ Rouen | UROTENSIN II FOR USE IN THE TREATMENT AND / OR PREVENTION OF PATHOLOGIES INVOLVING GASTRIC MOTILITY |
Also Published As
Publication number | Publication date |
---|---|
EP1233774A1 (en) | 2002-08-28 |
EP1233774A4 (en) | 2004-06-16 |
WO2001037780A8 (en) | 2001-11-08 |
JP2003527341A (en) | 2003-09-16 |
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