Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
  • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
  • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • 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
  • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

• the present invention relates to chromans, processes for their preparation and their use in medicaments, in particular as agents for combating diseases of the central nervous system.
• the invention therefore relates to new compounds of the general formula (I)
• the Neritatien according to the invention can exist in stereoisomeric forms that either behave like image and mirror image (enantiomers), or that do not behave like image and mirror image (diastereomers).
• the invention relates to both
• Enantiomers or diastereomers or their respective mixtures These mixtures of the enantiomers and diastereomers can be separated into the stereoisomerically uniform constituents in a known manner.
• inventive compounds can also be in the form of their salts, hydrates and / or solvates.
• preferred salts are physiologically acceptable salts of the Neritatien according to the invention.
• Physiologically acceptable salts of the Neritatien invention can be acid addition salts of the Neritatien with mineral acids, carboxylic acids or sulfonic acids.
• salts with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, eansulfonic acid, toluenesulfonic acid, benzenesulfonic acid, ⁇ aphthalenedisulfonic acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid, fumaric acid, maleic acid or benzoic acid are particularly preferred. Hydrates of the compounds according to the invention are stoichiometric compositions of the compounds or its salts with water.
• Solvates of the compounds according to the invention are stoichiometric compositions of the compounds or its salts with solvent, optionally in an isomeric form, and their salts.
• Preferred compounds of the general formula (I) are those which have the R configuration in the 2-position of the chroman radical.
• inventive compounds of the general formula (I) can be prepared as illustrated in the following formula schemes and as described in the exemplary embodiments:
• the compounds according to the invention can be used as active ingredients in pharmaceuticals.
• the substances according to the invention have a particularly high affinity for cerebral 5-hydroxy-tryptamine receptors of the 5-HTi A type.
• Active substances for combating diseases which are characterized by disorders of the serotoninergic system, in particular when receptors of the 5-HT ⁇ type are involved. They are therefore suitable for the treatment of diseases of the central nervous system such as anxiety, tension and depression, central nervous system-related sexual dysfunctions and sleep disorders, as well as for
• the compounds of the general formula (I) and the pharmaceutical compositions derived from these compounds, as for other 5HT]! A ligands shown in WO 99/26621 are used for the post-acute therapeutic treatment of various neurological conditions in which various cell types of the nervous system have been degenerated and / or damaged as a result of neurodegenerative diseases or interventions or exposures.
• compounds of the general formula (T) can be used for the treatment of secondary conditions in which damage to cells of the nervous system due to surgical interventions, infections, exposure to toxic agents, tumors, nutritional deficits or metabolic diseases has occurred.
• compounds of the general Formula (I) are used to treat the consequences of neurodegenerative diseases, such as Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, substance abuse or drug addiction (alcohol, cocaine, heroin, amphetamine or the like), spinal cord diseases and / or - Injuries, dystrophy or degeneration of the neural retina (retinopathies) and peripheral neuropathies, such as diabetic neuropathy and / or peripheral neuropathies induced by toxins.
• compounds of general formula (I) can be used in conjunction with surgical implantation of tissues and / or prostheses for the treatment of Alzheimer's disease or other neurological diseases and / or malfunctions in which an implantation is indicated.
• Rat hippocampal membranes measured. It was found that the Neritatien compete with the radioligand for the binding and inhibit it.
• the left cerebral artery in rats is occluded by electrocoagulation.
• the resulting infarct volume in cortical (subcortical) regions that are supplied by the middle cerebral artery is used as a measure of the size of the stroke-induced neuronal damage.
• Substance application After occlusion as a continuous IV. Infusion (4 hours) of the test substance, starting immediately after the operation. The animals are sacrificed for evaluation 7 days after the operation.
• the present invention also includes pharmaceutical preparations which, in addition to inert, non-toxic, pharmaceutically suitable auxiliaries and excipients, contain one or more Neritatien of the general formula (I), or which consist of a or several active ingredients of the formula (I), and processes for the preparation of these preparations.
• the active compounds of the formula (I) should be present in these preparations in a concentration of 0.1 to 99.5% by weight, preferably 0.5 to 95% by weight, of the total mixture.
• the pharmaceutical preparations can also contain other pharmaceutical active ingredients.
• the pharmaceutical preparations listed above can be prepared in a customary manner by known methods, for example using the excipient or excipients.
• the residue is purified by chromatography (silica gel, mobile phase dichloromethane / ethanol, gradient 1: 0 to 5: 1).
• the product fractions thus obtained are freed from the solvent by concentration, taken up in ethanol and carefully mixed with 10 ml of a 4 N solution of HCl gas in ethanol. After cooling in ice, the solid obtained is suction filtered, dissolved in 550 ml of hot heat and treated with activated carbon. After filtration, the mixture is concentrated to about 100 ml. The crystals which precipitate are filtered off with suction and dried in vacuo.
• the raw product is purified by HPLC chromatography under the following conditions: Nucleosil ® 100 C-18 column, 125 x 16 mm (particle size 7 ⁇ m), column temperature room temperature, eluent 85% acetonitrile / 15% water (v / v), Flow 6 ml / min., UV detection at 230 nm.
• the product-containing fractions are combined and evaporated to dryness.
• the residue is dissolved in 2.5 ml of ethanol and 6 ml of acetone and again evaporated to dryness.
• the product is dried in a desiccator over blue gel.

Landscapes

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

Priority Applications (4)

Applications Claiming Priority (2)

Publications (1)

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Family Applications (1)

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Cited By (2)

Families Citing this family (1)

Citations (3)

• 2001
  • 2001-10-01 DE DE10148425A patent/DE10148425A1/de not_active Withdrawn
• 2002
  • 2002-09-18 EP EP02767489A patent/EP1434777A1/de not_active Withdrawn
  • 2002-09-18 JP JP2003532498A patent/JP2005507901A/ja not_active Withdrawn
  • 2002-09-18 WO PCT/EP2002/010447 patent/WO2003029250A1/de not_active Ceased
  • 2002-09-18 US US10/490,315 patent/US6919360B2/en not_active Expired - Fee Related
  • 2002-09-18 CA CA002462142A patent/CA2462142A1/en not_active Abandoned

Patent Citations (3)

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