WO2001045694A1 - Urotensin-ii receptor antagonists - Google Patents
Urotensin-ii receptor antagonists Download PDFInfo
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- WO2001045694A1 WO2001045694A1 PCT/US2000/034574 US0034574W WO0145694A1 WO 2001045694 A1 WO2001045694 A1 WO 2001045694A1 US 0034574 W US0034574 W US 0034574W WO 0145694 A1 WO0145694 A1 WO 0145694A1
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- chloro
- phenyl
- ethoxy
- dimethylamino
- benzenesulfonamide
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- 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
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- 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
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- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/15—Six-membered rings
- C07D285/16—Thiadiazines; Hydrogenated thiadiazines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
Definitions
- the present invention relates to sulfonamides, pharmaceutical compositions containing them and their use as urotensin II antagonists
- 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.
- Urotensin-II receptor 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.
- this invention provides for sulfonamides and pharmaceutical compositions containing them.
- this invention provides for the use of sulfonamides as antagonists of urotensin II, and as inhibitors of urotensin II.
- this invention provides for the use of sulfonamides for treating conditions associated with urotensin II imbalance.
- this invention provides for the use of sulfonamides 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 urotensin antagonist may be administered alone or in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of endothelin receptor antagonists, angiotensin converting enzyme (ACE) inhibitors, vasopeptidase inhibitors, diuretics, digoxin, and dual non-selective ⁇ -adrenoceptor and o - adrenoceptor antagonists.
- agents being selected from the group consisting of endothelin receptor antagonists, angiotensin converting enzyme (ACE) inhibitors, vasopeptidase inhibitors, diuretics, digoxin, and dual non-selective ⁇ -adrenoceptor and o - adrenoceptor antagonists.
- ACE angiotensin converting enzyme
- the present invention provides for compounds of Formula(I):
- Ri is phenyl, benzothiophenyl, thienyl, furyl, pyrrolyl, pyridinyl, benzthiadiazoyl, benzoxadiazoyl, quinolinyl, or naphthyl, all of which may be substituted or unsubstituted by one, two, three, four or five of the following: halogen, methoxy, OH, NO2, YCF3, C ] _4 alkyl, C ( o_4)alkylC0 C ( o-4)alkyl, cyano, cycloQ ] _4)alkylenedioxy, or dimethylamino; R2 is halogen, CN or methyl;
- R3 and R4 are independently hydrogen, C j_ 0 alkyl or benzyl; or with the nitrogen form a pyrrolidine or piperidine ring:
- X is O or CH 2 ;
- Y is a bond or O; provided the compound of Formula (I) is not 5-Chloro-3-methyl-benzo[b]thiophene-2- sulfonic acid [3-(2-dimethylamino-ethoxy)-4-iodo-phenyl]-amide; or a pharmaceutically acceptable salt thereof.
- alkyl includes all straight chain and branched isomers. Representative examples thereof include methyl, ethyl, rc-propyl, wo-propyl, n-butyl, sec- butyl, w ⁇ -butyl, t-butyl, n-pentyl and n-hexyl.
- Tialogen' and halo' include fluorine, chlorine, bromine and iodine and fluoro, chloro, bromo and iodo, respectively.
- 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.
- Ri is phenyl, thienyl, pyridinyl, benzthiadiazoyl, benzoxadiazoyl, or naphthyl, all of which may be substituted or unsubstituted by one, two, or three of the following: halogen, methoxy, NO2, YCF3, or C ] _4 alkyl.
- R 2 is halogen
- R3 is alkyl; more preferably R3 is methyl or ethyl.
- R4 is alkyl; more preferably R4 is methyl or ethyl.
- X is O.
- Y is a bond.
- Preferred Compounds are: N-[4-Iodo-3-(2-dimethylamino-ethoxy)-phenyl]-3,4-dimethoxy-benzenesulfonamide;
- More preferred compounds are: N-[4-Chloro-3-(2-dimethylamino-ethoxy)-phenyl]-3,4-dimethoxy-benzenesulfonamide;
- 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.
- Compounds of Formula (I) and their pharmaceutically acceptable salts which are active when given orally can be formulated as syrups, tablets, capsules and lozenges.
- 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, glycerine 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 incorporated 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.
- a parenterally acceptable oil for example polyethylene glycol, polyvinylpyrrolidone, lecithin, arachis oil, or sesame oil.
- 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.
- 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.
- the composition is in unit dosage form, for example a tablet, capsule or metered aerosol dose, so that the patient may administer to themselves a single dose.
- Each dosage unit for oral administration contains suitably from 0.1 mg to 500 mg/Kg, and preferably from 1 mg to 100 mg/Kg, and each dosage unit for parenteral administration contains suitably from 0.1 mg to 100 mg, of a compound of Formula (I) or a pharmaceutically acceptable salt thereof calculated as the free acid.
- Each dosage unit for intranasal administration contains suitably 1-400 mg and preferably 10 to 200 mg per person.
- a topical formulation contains suitably 0.01 to 1.0% of a compound of Formula
- the daily dosage regimen for oral administration is suitably about 0.01 mg/Kg to 40 mg/Kg, of a compound of Formula (I) or a pharmaceutically acceptable salt thereof calculated as the free acid.
- the daily dosage regimen for parenteral administration is suitably about 0.001 mg/Kg to 40 mg/Kg, of a compound of the Formula (I) or a pharmaceutically acceptable salt thereof calculated as the free acid.
- the daily dosage regimen for intranasal administration and oral inhalation is suitably about 10 to about 500 mg/person.
- the active ingredient may be administered from 1 to 6 times a day, sufficient to exhibit the desired activity.
- sulphonamide 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.
- the urotensin antagonist may be administered alone or in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of endothelin receptor antagonists, angiotensin converting enzyme (ACE) inhibitors, vasopeptidase inhibitors, diuretics, digoxin, and dual non-selective ⁇ -adrenoceptor and ⁇ j - adrenoceptor antagonists.
- ACE angiotensin converting enzyme
- 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 " ' 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.
- 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.
- Inositol phosphates assays HEK-293-GPR14 cells in T150 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 in 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 l ⁇ 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.
- the mixture was filtered through Celite ® and the residue washed well with hot ethyl acetate.
- the mixture was washed 2 x ethyl acetate, and the aqueous portion basified to pH 11 using solid potassium carbonate. It was extracted 2 x ethyl acetate, dried over magnesium sulfate, filtered, and concentrated to afford the product (1.53 g, 57%) as a rust-colored oil.
- Formulations for pharmaceutical use incorporating compounds of the present invention can be prepared in various forms and with numerous excipients. Examples of such formulations are given below. Tablets/Ingredients Per Tablet
- Step 1 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 3 The wet mass is converted to granules by passing it through an oscillating granulator using a No. 8 mesh (2.38 mm) screen.
- 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.
- 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.
- Parenteral Formulation A pharmaceutical composition for parenteral administration is prepared by dissolving an appropriate amount of a compound of formula I in polyethylene glycol with heating. This solution is then diluted with water for injections Ph Eur. (to 100 ml). The solution is then sterilized by filtration through a 0.22 micron membrane filter and sealed in sterile containers.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
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CA002394603A CA2394603A1 (en) | 1999-12-21 | 2000-12-19 | Urotensin-ii receptor antagonists |
AU24418/01A AU2441801A (en) | 1999-12-21 | 2000-12-19 | Urotensin-ii receptor antagonists |
EP00988185A EP1248607A4 (en) | 1999-12-21 | 2000-12-19 | Urotensin-ii receptor antagonists |
JP2001546633A JP2003518057A (en) | 1999-12-21 | 2000-12-19 | Urotensin-II receptor antagonist |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US17280799P | 1999-12-21 | 1999-12-21 | |
US60/172,807 | 1999-12-21 |
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WO2001045694A1 true WO2001045694A1 (en) | 2001-06-28 |
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PCT/US2000/034574 WO2001045694A1 (en) | 1999-12-21 | 2000-12-19 | Urotensin-ii receptor antagonists |
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EP (1) | EP1248607A4 (en) |
JP (1) | JP2003518057A (en) |
AU (1) | AU2441801A (en) |
CA (1) | CA2394603A1 (en) |
WO (1) | WO2001045694A1 (en) |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002015934A1 (en) * | 2000-08-25 | 2002-02-28 | Takeda Chemical Industries, Ltd. | Preventives and remedies for central nervous system diseases |
WO2002076979A1 (en) * | 2001-03-27 | 2002-10-03 | Actelion Pharmaceuticals Ltd | 1,2,3,4-tetrahydroisoquinolines derivatives as urotensin ii receptor antagonists |
WO2002078641A2 (en) * | 2001-03-29 | 2002-10-10 | Smithkline Beecham Corporation | Pyrrolidine sulfonamides |
WO2002090337A1 (en) * | 2001-05-07 | 2002-11-14 | Smithkline Beecham Corporation | Sulfonamides |
EP1310490A1 (en) * | 2000-07-04 | 2003-05-14 | Takeda Chemical Industries, Ltd. | Gpr14 antagonist |
WO2004007472A1 (en) * | 2002-07-10 | 2004-01-22 | Ono Pharmaceutical Co., Ltd. | Ccr4 antagonist and medicinal use thereof |
EP1385495A2 (en) * | 2001-05-07 | 2004-02-04 | SmithKline Beecham Corporation | Sulfonamides |
EP1387679A1 (en) * | 2001-05-07 | 2004-02-11 | SmithKline Beecham Corporation | Sulfonamides |
EP1399137A1 (en) * | 2001-05-07 | 2004-03-24 | SmithKline Beecham Corporation | Sulfonamides |
WO2004031181A1 (en) * | 2002-10-07 | 2004-04-15 | Glaxo Group Limited | Sulfonamide derivatives as antipsychotic agents |
WO2007076875A2 (en) * | 2006-01-06 | 2007-07-12 | Aarhus Universitet | Compounds acting on the serotonin transporter |
US7375227B2 (en) | 2001-12-04 | 2008-05-20 | Actelion Pharmaceuticals Ltd. | Quinoline derivatives |
US7750161B2 (en) | 2003-09-26 | 2010-07-06 | Daniel Bur | Pyridine derivatives |
WO2010048332A3 (en) * | 2008-10-22 | 2010-07-22 | Acucela, Inc. | Compounds for treating ophthalmic diseases and disorders |
US8067601B2 (en) | 2004-10-12 | 2011-11-29 | Actelion Pharmaceticals Ltd. | 1-[2-(4-benzyl-4-hydroxy-piperidin-1 -yl )-ethyl]-3-(2-methyl-quinolin- 4-yl)- urea as crystalline sulfate salt |
Citations (1)
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US5795892A (en) * | 1994-08-30 | 1998-08-18 | Boehringer Manneim Gmbh | 4-aminopyridazines, method of preparing them and drugs containing these compounds |
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DZ2376A1 (en) * | 1996-12-19 | 2002-12-28 | Smithkline Beecham Plc | New sulfonamide derivatives process for their preparation and pharmaceutical compositions containing them. |
-
2000
- 2000-12-19 JP JP2001546633A patent/JP2003518057A/en not_active Withdrawn
- 2000-12-19 EP EP00988185A patent/EP1248607A4/en not_active Withdrawn
- 2000-12-19 AU AU24418/01A patent/AU2441801A/en not_active Abandoned
- 2000-12-19 WO PCT/US2000/034574 patent/WO2001045694A1/en not_active Application Discontinuation
- 2000-12-19 CA CA002394603A patent/CA2394603A1/en not_active Abandoned
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US5795892A (en) * | 1994-08-30 | 1998-08-18 | Boehringer Manneim Gmbh | 4-aminopyridazines, method of preparing them and drugs containing these compounds |
Non-Patent Citations (1)
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See also references of EP1248607A4 * |
Cited By (25)
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EP1310490A1 (en) * | 2000-07-04 | 2003-05-14 | Takeda Chemical Industries, Ltd. | Gpr14 antagonist |
EP1310490A4 (en) * | 2000-07-04 | 2004-03-17 | Takeda Chemical Industries Ltd | Gpr14 antagonist |
WO2002015934A1 (en) * | 2000-08-25 | 2002-02-28 | Takeda Chemical Industries, Ltd. | Preventives and remedies for central nervous system diseases |
WO2002076979A1 (en) * | 2001-03-27 | 2002-10-03 | Actelion Pharmaceuticals Ltd | 1,2,3,4-tetrahydroisoquinolines derivatives as urotensin ii receptor antagonists |
US6815451B2 (en) | 2001-03-27 | 2004-11-09 | Actelion Pharmaceuticals Ltd. | 1,2,3,4-Tetrahydroisoquinolines derivatives as urotensin II receptor antagonists |
WO2002078641A3 (en) * | 2001-03-29 | 2002-11-28 | Smithkline Beecham Corp | Pyrrolidine sulfonamides |
WO2002078641A2 (en) * | 2001-03-29 | 2002-10-10 | Smithkline Beecham Corporation | Pyrrolidine sulfonamides |
WO2002090337A1 (en) * | 2001-05-07 | 2002-11-14 | Smithkline Beecham Corporation | Sulfonamides |
EP1385495A4 (en) * | 2001-05-07 | 2005-12-21 | Smithkline Beecham Corp | Sulfonamides |
EP1385495A2 (en) * | 2001-05-07 | 2004-02-04 | SmithKline Beecham Corporation | Sulfonamides |
EP1387679A1 (en) * | 2001-05-07 | 2004-02-11 | SmithKline Beecham Corporation | Sulfonamides |
EP1399137A1 (en) * | 2001-05-07 | 2004-03-24 | SmithKline Beecham Corporation | Sulfonamides |
EP1387679A4 (en) * | 2001-05-07 | 2004-08-11 | Smithkline Beecham Corp | Sulfonamides |
EP1399137A4 (en) * | 2001-05-07 | 2005-12-14 | Smithkline Beecham Corp | Sulfonamides |
US7375227B2 (en) | 2001-12-04 | 2008-05-20 | Actelion Pharmaceuticals Ltd. | Quinoline derivatives |
WO2004007472A1 (en) * | 2002-07-10 | 2004-01-22 | Ono Pharmaceutical Co., Ltd. | Ccr4 antagonist and medicinal use thereof |
US7122538B2 (en) | 2002-10-07 | 2006-10-17 | Glaxo Group Limited | Sulfonamide derivatives as antipsychotic agents |
WO2004031181A1 (en) * | 2002-10-07 | 2004-04-15 | Glaxo Group Limited | Sulfonamide derivatives as antipsychotic agents |
US7750161B2 (en) | 2003-09-26 | 2010-07-06 | Daniel Bur | Pyridine derivatives |
US8067601B2 (en) | 2004-10-12 | 2011-11-29 | Actelion Pharmaceticals Ltd. | 1-[2-(4-benzyl-4-hydroxy-piperidin-1 -yl )-ethyl]-3-(2-methyl-quinolin- 4-yl)- urea as crystalline sulfate salt |
WO2007076875A2 (en) * | 2006-01-06 | 2007-07-12 | Aarhus Universitet | Compounds acting on the serotonin transporter |
WO2007076875A3 (en) * | 2006-01-06 | 2007-11-15 | Univ Aarhus | Compounds acting on the serotonin transporter |
WO2010048332A3 (en) * | 2008-10-22 | 2010-07-22 | Acucela, Inc. | Compounds for treating ophthalmic diseases and disorders |
US8674137B2 (en) | 2008-10-22 | 2014-03-18 | Acucela Inc. | Compounds for treating ophthalmic diseases and disorders |
US9193669B2 (en) | 2008-10-22 | 2015-11-24 | Acucela Inc. | Compounds for treating ophthalmic diseases and disorders |
Also Published As
Publication number | Publication date |
---|---|
EP1248607A1 (en) | 2002-10-16 |
CA2394603A1 (en) | 2001-06-28 |
EP1248607A4 (en) | 2004-10-06 |
AU2441801A (en) | 2001-07-03 |
JP2003518057A (en) | 2003-06-03 |
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