WO1998032738A1 - Nouveaux composes a effet haemoregulateur - Google Patents

Nouveaux composes a effet haemoregulateur Download PDF

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Publication number
WO1998032738A1
WO1998032738A1 PCT/EP1998/000511 EP9800511W WO9832738A1 WO 1998032738 A1 WO1998032738 A1 WO 1998032738A1 EP 9800511 W EP9800511 W EP 9800511W WO 9832738 A1 WO9832738 A1 WO 9832738A1
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Prior art keywords
group
optionally
nmr
formula
alkyl
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PCT/EP1998/000511
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German (de)
English (en)
Inventor
Johann Hiebl
Hermann Kollmann
Franz Rovenszky
Michael Hartmann
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Nycomed Austria Gmbh
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Publication date
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Priority to EP98908028A priority Critical patent/EP0958283A1/fr
Priority to JP53161898A priority patent/JP2001509795A/ja
Publication of WO1998032738A1 publication Critical patent/WO1998032738A1/fr
Priority to NO993650A priority patent/NO993650D0/no
Priority to NO993782A priority patent/NO993782D0/no

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • 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 invention relates to new compounds with hemoregulatory activity, which can be used to stimulate haematopoiesis and to treat viral, bacterial and fungal infections.
  • the haematopoietic system is a lifelong cell renewal process in which a defined stem cell population induces a larger population of mature, differentiated blood cells (Dexter TM. Stern cells in normal growth and disease, Br. Med. J. 1987, 195: 1192-1194) with at least 7 different cell lines (erythrocytes, basophilic granulocytes, neutrophilic granulocytes, monocytes / macrophages, osteoclasts and lymphocytes (Metcalf D. The Molecular Control of Biood Cells, 1988, Harvard University Press, Cambridge, MA).
  • stem cells can be found in the myelopoetic cells of the bone marrow, as well as in the epithelial and epidermal cells, so the stem cells are ultimately responsible for the regeneration of the bone marrow after treatment with cytostatic compounds or after a bone marrow transplant.
  • CSF colony-stimulating factors
  • G-CSF granulocyte-colony-stimulating factor
  • M-CSF macrophage-colony-stimulating factor
  • GM-CSF granulocyte-macrophage- colony stimulating factor
  • Interleukin 11 (IL-11) (Paul et al “Proc. Natl. Acad. Sci. USA Vol. 87, p. 7521, born 1990), lactoferrin (Broxmeyer et al., Blood Cells Vol. 11, p. 429, born 1986), prostaglandins (Pelus et al., J. Immunol., Vol. 140, p. 479, born 1988), ⁇ -, ß - and ⁇ -interferon (Pelus et al. and Broxmeyer et al., J.
  • the invention therefore relates to compounds of the formula (I)
  • R is hydrogen, a saturated or unsaturated C 1-18 alkyl radical, triallyl kylsilyl, Diphenylalkylsilyl, a benzyl radical or a cycloalkyl radical, the optionally substituted one or more times by halogen or alkoxy NEN be Kgs ⁇ , or
  • R 1 is an N-terminal peptide residue of 1-10 optionally correspondingly ge ⁇ protected natural or unnatural ⁇ - or ß-amino acids
  • R 2 and R 2 'are independently tert-butyloxycarbonyl, benzyloxycarbonyl carbonyl, fluorenyloxycarbonyl, or a group (C O) -R 3 , where R 3 C 1-4 alkyl, phenyl, or a 5-10 membered mono- or bicyclic saturated, fully or partially unsaturated heterocyclic ring system with up to 4 heteroatoms such as N, O, S, which may be substituted one, more than once or mixed can by alkyl, alkoxy, alkoxyalkyl, oxo, oxime, O-alkyloxime, hydroxy, amino, monoalkylamino, dialkylamino, acylamino or aminoacyl, 7, 8, 9, 10-membered moncyclic ring systems being excluded, or
  • R 2 ' is hydrogen
  • R 2 is tert-butyloxycarbonyl, benzyloxycarbonyl, fluorenyloxycarbonyl, or a group
  • R 3 is C 1-4 alkyl, phenyl, or a 5-10 membered mono- or bicyclic saturated, fully or partially unsaturated heterocyclic ring system with up to 4 heteroatoms such as N, O, S, which may optionally be mono-, polysubstituted or mixed by alkyl, alkoxy, alkoxyalkyl, oxo, oxime, O-alkyloxime, hydroxy, amino, monoalkylamino, dialkylamino, acylamino or aminoacyl, where 7, 8, 9, 10-membered moncyclic Ring systems are excluded, or
  • Q is a group - (CH 2 ) m , where m is an integer from 0 to 20 or a group - (CH 2 ) n -X- (CH 2 ) p - where n and p independently of one another are a number from 0 to 14, and one or more hydrogen atoms by alkyl , or halogen or alkoxy or hydroxy may be substituted
  • Z O or S q is an integer from 1 to 4
  • r is an integer from 1 to 3.
  • R. denotes a group O- R, where R. ' Hydrogen, a straight-chain or branched C 1-18 alkyl radical, for example methyl, ethyl, propyl, i-propyl, butyl, pentyl, hexyl, heptyl, octyl, 1-methylethyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl , 2,2-dimethylpropyl, 1,2-dimethylpropyl, u.
  • R. ' Hydrogen a straight-chain or branched C 1-18 alkyl radical, for example methyl, ethyl, propyl, i-propyl, butyl, pentyl, hexyl, heptyl, octyl, 1-methylethyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl , 2,2-dimethylpropyl, 1,2-
  • a benzyl radical or a cycloalkyl radical for example a cyclopentyl or cyclohexyl radical or trialkylsilyl, or diphenylalkylsilyl.
  • These radicals can optionally be mixed one or more times or mixed by halogen, for example F or Cl, including perhalogenated radicals, or by alkoxy, for example methoxy, ethoxy and the like.
  • halogen for example F or Cl, including perhalogenated radicals, or by alkoxy, for example methoxy, ethoxy and the like.
  • alkoxy for example methoxy, ethoxy and the like.
  • R 1 can also mean an N-terminal peptide residue of 1-10 natural or unnatural ⁇ - or ⁇ -amino acids, which can optionally be protected by appropriate protective groups.
  • amino acids from which such a peptide residue can be constructed are, for example, ⁇ -alanine, aspartic acid, glutamic acid, lysine, pyroglutamic acid, serine, and the like.
  • R 3 is a C 1-4 alkyl radical, phenyl, or a 5-10 membered mono- or bicyclic saturated, fully or partially unsaturated heterocycl
  • radicals are cyclopentyl, cyclopentenyl, cyclopentadienyl, cyclohexyl, cyclohexenyl, tetrahydrofuryl, thiolanyl, pyrrolidinyl, dihydrofuryl, dihydrothienyl, dihydropyrrolyl, dihydrooxazolyl, dihydrothiazolyl, dihydropyropyryl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl morpholinyl, piperazinyl, dihydropyranyl, tetrahydropyridinyl, isoxazolyl, oxa- zolyl, isothiazolyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, pyrany
  • Examples of such amino acids from which such a peptide residue can be constructed are, for example, ⁇ -alanine, aspartic acid, glutamic acid, lysine, pyroglutamic acid, serine and the like. the like.
  • Q represents a group - (CH 2 ) m , where m represents an integer from 0 to 20 or a group - (CH 2 ) n -X- (CH 2 ) p - where n and p independently of one another represent a number of 0 - 14 mean, and one or more hydrogen atoms can be substituted by alkyl, or halogen or alkoxy or hydroxy.
  • Z O or S q is an integer from 1 to 4 and r is an integer from 1 to 3.
  • the invention further relates to a process for the preparation of the compounds of the formula I, which is characterized in that a) a dialdehyde of the formula II
  • R 1 R 2 and R 2 ', which have the meanings given above and R 5 is methyl or ethyl
  • the mixture was then poured onto ethyl acetate or methylene chloride and washed with a suitable extractant, for example dilute HCl solution.
  • a suitable extractant for example dilute HCl solution.
  • the organic phase was separated off and the aqueous phase was washed with a suitable extractant, for example ethyl acetate or methylene chloride.
  • the combined organic phases were dried with a suitable drying agent, for example Na 2 SO 4 , filtered and the filtrate was concentrated in vacuo. After crystallization from a suitable solvent, for example from toluene / ethyl acetate, the desired di-unsaturated end product was obtained.
  • the mixture was then extracted with an acidic solution, for example 1N HCl solution, and then washed with a suitable extracting agent, for example saturated NaCl solution.
  • a suitable extracting agent for example saturated NaCl solution.
  • the organic phase was dried with a suitable drying agent, for example Na 2 SO 4 , and filtered.
  • the filtrate was concentrated in vacuo and then recrystallized in a suitable solvent.
  • the compounds prepared by process A or B were dissolved in a water-miscible solvent, for example methanol, dioxane, tetrahydrofuran.
  • aqueous LiOH solution (2.5 equivalents) was then added and this mixture was stirred until no more starting product was detectable.
  • the reaction solution was mixed with an acidic solution, for example 1N HCl solution or 5% KHSO 4 solution, the precipitate formed was filtered off and recrystallized from a suitable solvent, for example methanol, CH 3 CN.
  • the compounds of the formula I obtained in this way can be converted into their pharmaceutically acceptable salts in a conventional manner using inorganic or organic bases.
  • Salt formation can be carried out, for example, by using a compound of the formula i in a suitable solvent, such as, for example, water, acetone, acetonitrile, benzene, dimethylformamide, dimethyl sulfoxide, chloroform, dioxane, methanol, ethanol, hexanol, ethyl acetate or in an aliphatic Dissolves ether, for example diethyl ether, or mixtures of such solvents, adds an at least equivalent amount of the desired base, ensures thorough mixing and, after the salt formation has ended, the precipitated salt is filtered off, lyophilized or the solvent solvent distilled off in vacuo. If necessary, the salts can be recrystallized after isolation.
  • a suitable solvent such as, for example, water, acetone, acetonitrile, benzen
  • Pharmaceutically acceptable salts are e.g. Metal salts, especially alkali metal or alkaline earth metal salts, such as sodium, potassium, magnesium or calcium salts.
  • Other pharmaceutical salts are, for example, easily crystallizing ammonium salts. These are derived from ammonia or organic amines such as mono-, di- or tri-lower (alkyl, cycloalkyl or hydroxyalkyl) amines, lower alkylenediamines or hydroxy or aryl-lower alkylammonium bases, e.g. Methylamine, diethylamine, triethylamine, ethylenediamine, tris (hydroxymethyl) aminomethane, benzyltrimethylammonium hydroxide and the like.
  • the compounds of formula I and their pharmaceutically acceptable salts are orally active and can influence the formation of hematopoietic factors.
  • the new compounds can be used in the form of customary galenical preparations as remedies for the treatment of diseases which are influenced by the hematopoietic system and viral, bacterial and fungal infections which occur as a result of such diseases, be used.
  • the invention therefore also relates to pharmaceutical preparations which contain the compounds of the formula I according to one of claims 1-2 or their salts, alone or mixed with other therapeutically valuable active substances, and also conventional pharmaceutical auxiliaries and / or carriers or diluents.
  • the compounds according to the invention can be in the form of tablets or capsules, which are a unit dose of the compound together with auxiliary agents. Contain substances and diluents such as corn starch, calcium carbonate, dicalcium phosphate, alginic acid, lactose, magnesium stearate, Primogel or talc, orally administered.
  • the tablets are produced in a conventional manner by granulating the ingredients and pressing, the capsules by filling into hard gelatin capsules of a suitable size.
  • suppositories which contain adjuvants, such as beeswax derivatives, polyethylene glycol or polyethylene glycol derivatives, linoleic or linolenic acid esters, together with a unit dose of the compound and can be administered rectally.
  • adjuvants such as beeswax derivatives, polyethylene glycol or polyethylene glycol derivatives, linoleic or linolenic acid esters
  • the compounds according to the invention can also be administered parenterally, for example by intramuscular, intravenous or subcutaneous injection.
  • parenteral administration they are best used in the form of a sterile aqueous solution, which can contain other solutes, such as tonic agents, pH adjusters, preservatives and stabilizers.
  • Distilled water can be added to the compounds and the pH can be adjusted to 3 to 6 using, for example, citric acid, lactic acid or hydrochloric acid.
  • Sufficiently dissolved substances, such as dextrose or saline, can be added to make the solution isotonic.
  • preservatives such as p-hydroxybenzoates, and stabilizers, such as EDTA
  • the solution thus obtained can then be sterilized and filled into sterile glass ampoules of a suitable size so that they contain the desired solution volume.
  • the compounds according to the invention can also be administered by infusion of a parenteral formulation as described above.
  • the daily dose value of a compound according to the invention is in the range from 0.001 to 100 mg per day for a typical adult patient of 70 kg. Therefore, tablets or capsules can usually contain 0.0003 to 30 mg of active compound, for example 0.01 to 5 mg, for oral administration up to included three times a day.
  • the dose may range from 0.001 to 100 mg per 70 kg per day, for example about 0.5 mg.
  • the invention also relates to a method for stimulating cell division, preferably myelopoiesis, characterized in that a therapeutically effective amount of a pharmaceutical composition as described above is administered to a patient.
  • Bone marrow cells were obtained from C57B1 / 6 female mice and in
  • the number of cell colonies is proportional to the number available
  • Another object of the invention is the use of the compounds obtained by one of process A or B for the production of optically active diaminodicarboxylic acid derivatives, which are a valuable starting product for the production of peptides, by enantioselective hydrogenation.
  • the corresponding process product from process A or B was dissolved in a suitable solvent, for example: oxygen-free methanol, dioxane, obtained by boiling under a nitrogen atmosphere under reduced pressure.
  • a suitable solvent for example: oxygen-free methanol, dioxane, obtained by boiling under a nitrogen atmosphere under reduced pressure.
  • the catalyst was added to this clear solution and the solution obtained was hydrogenated under elevated pressure at room temperature in a Parr apparatus.
  • the solution was filtered through silica gel to remove the dissolved catalyst.
  • the eluate was concentrated under vacuum and the crude product obtained was dissolved in a suitable solvent, for example dioxane / water, and treated with LiOH at room temperature.
  • the mixture was then concentrated again in vacuo and water was added, whereupon the solution was acidified with a suitable acid, for example with aqueous KHS0 4 solution.
  • the precipitate thus obtained was filtered, washed with cold water and dried.
  • the mixture was then recrystallized from a suitable solvent,
  • Example 2 f2Z, 4ZV2.5-bis-yridin-2-carbonylaminoV-octa-2.4-dienedioic acid
  • Method A 80%.
  • Method B 78%, mp 243-247 ° C.
  • Example 15 1,4-bis- [2- (acetylamino) -2- (methoxycarbonyl) ethenyl] benzene Obtained according to process B from para-phthalaldehyde and Ac-phosphonoglycine methyl ester. Yield: 80%, Mp: 275 ° C (decomposition).
  • 1 H NMR 400 MHz, d 6 -DMSO) ⁇ 1.99 (s, 6, 2 COCH 3 ), 3.70 (s, 6, 2 OMe), 7.16 (s, 2, 2 CH), 7.62 (s, 4 , aromat.-H), 9.51 (s, 2, 2 NH).
  • Example 21 The procedure was analogous to Example 20, but Rh [(COD-S, S-Me-DuPHOS) CF 3 S0 4 ] was used as the catalyst. Optical purity: 97.1% de
  • Rh [(COD-S, S-Et-DuPHOS) CF 3 S0 4 ] was used as the catalyst.
  • Rh [(COD-S, S-Et-DuPHOS) CF 3 S0 4 ] was used as the catalyst.
  • Example 1 The compound according to Example 1 was subjected to the test described above for determining the HSF and had an activity of 2.97E + 5 HSF units / mL.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne les composés de la formule (I), qui ont une action haemorégulatrice, ainsi que leur utilisation et le procédé de production.
PCT/EP1998/000511 1997-01-27 1998-01-27 Nouveaux composes a effet haemoregulateur WO1998032738A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP98908028A EP0958283A1 (fr) 1997-01-27 1998-01-27 Nouveaux composes a effet haemoregulateur
JP53161898A JP2001509795A (ja) 1997-01-27 1998-01-27 血液調節作用を有する新規化合物
NO993650A NO993650D0 (no) 1997-01-27 1999-07-27 Nye forbindelser med hemoregulerende effekt
NO993782A NO993782D0 (no) 1997-01-27 1999-08-04 Nye forbindelser med hemoregulerende effekt

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT10797 1997-01-27
ATA107/97 1997-01-27

Publications (1)

Publication Number Publication Date
WO1998032738A1 true WO1998032738A1 (fr) 1998-07-30

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Application Number Title Priority Date Filing Date
PCT/EP1998/000511 WO1998032738A1 (fr) 1997-01-27 1998-01-27 Nouveaux composes a effet haemoregulateur

Country Status (4)

Country Link
EP (1) EP0958283A1 (fr)
JP (1) JP2001509795A (fr)
NO (2) NO993650D0 (fr)
WO (1) WO1998032738A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6235727B1 (en) * 1998-07-16 2001-05-22 Aventis Pharma Deutschland Gmbh Sulfonylaminophosphinic and sulfonylaminophosphinic acid derivatives, methods for their preparation and use

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996019457A1 (fr) * 1994-12-20 1996-06-27 Nycomed Imaging As Derives de pyridine et d'acide pyrazinedicarboxylique, utilises comme regulateurs de la proliferation cellulaire
WO1997017850A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hematoregulateurs
WO1997017965A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hemoregulateurs
WO1997017851A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hemoregulateurs
WO1997017959A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hemoregulatoires
WO1997017968A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hemoregulateurs

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996019457A1 (fr) * 1994-12-20 1996-06-27 Nycomed Imaging As Derives de pyridine et d'acide pyrazinedicarboxylique, utilises comme regulateurs de la proliferation cellulaire
WO1997017850A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hematoregulateurs
WO1997017965A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hemoregulateurs
WO1997017851A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hemoregulateurs
WO1997017959A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hemoregulatoires
WO1997017968A1 (fr) * 1995-11-13 1997-05-22 Smithkline Beecham Corporation Composes hemoregulateurs

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Title
A.S. CARLSTRÖM ET AL.: "Palladium catalysed bis-coupling of dihaloaromatics with 2-amidoacrylates", JOURNAL OF ORGANIC CHEMISTRY., vol. 56, no. 3, 1991, EASTON US, pages 1289 - 1293, XP002066484 *
B. BASU ET AL.: "Catalytic asymmetric synthesis of bis-armed aromatic amino acid derivatives.", ACTA CHEMICA SCANDINAVICA. SERIES B - ORGANIC CHEMISTRY AND BIOCHEMISTRY., vol. 50, no. 4, 1996, COPENHAGEN DK, pages 316 - 322, XP002066482 *
CHEMICAL ABSTRACTS, vol. 123, no. 25, 18 December 1995, Columbus, Ohio, US; abstract no. 339321u, Z.-L. XU ET AL.: "Ester exchange reaction of azlactones catalysed by sodium acetate." page 1104; XP002066485 *
U. SCHMIDT ET AL.: "Amino acids and peptides ; XLIII.", SYNTHESIS., no. 1, 1984, STUTTGART DE, pages 53 - 60, XP002066483 *
YOUJI HUAXUE, vol. 15, no. 3, 1995, SHANGHAI, pages 292 - 295 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6235727B1 (en) * 1998-07-16 2001-05-22 Aventis Pharma Deutschland Gmbh Sulfonylaminophosphinic and sulfonylaminophosphinic acid derivatives, methods for their preparation and use
US6500811B2 (en) 1998-07-16 2002-12-31 Aventis Pharma Deutschland Gmbh Sulfonylaminophosphinic and sulfonylaminophosphonic acid derivatives, methods for their preparation and use

Also Published As

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NO993782D0 (no) 1999-08-04
EP0958283A1 (fr) 1999-11-24
NO993650L (no) 1999-07-27
NO993650D0 (no) 1999-07-27
JP2001509795A (ja) 2001-07-24

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