WO2000038692A1 - Remedes contre la mucoviscidose contenant des derives de la vitamine d¿3? - Google Patents

Remedes contre la mucoviscidose contenant des derives de la vitamine d¿3? Download PDF

Info

Publication number
WO2000038692A1
WO2000038692A1 PCT/JP1999/007229 JP9907229W WO0038692A1 WO 2000038692 A1 WO2000038692 A1 WO 2000038692A1 JP 9907229 W JP9907229 W JP 9907229W WO 0038692 A1 WO0038692 A1 WO 0038692A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
compound
carbonyl group
derivative
vitamin
Prior art date
Application number
PCT/JP1999/007229
Other languages
English (en)
Japanese (ja)
Inventor
Kazuya Takenouchi
Qingzhi Gao
Yasuhiro Takano
Original Assignee
Teijin Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Teijin Limited filed Critical Teijin Limited
Priority to AU17986/00A priority Critical patent/AU1798600A/en
Publication of WO2000038692A1 publication Critical patent/WO2000038692A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • 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

Definitions

  • the present invention relates to cystic fibrosis pulmonary disorder treatment agent using useful bi evening Min 0 3 derivative or solvate thereof pharmaceutically permissible as a medicine. More specifically, the present invention relates to a therapeutic agent for cystic fibrosis pulmonary disorder comprising, as an active ingredient, a 1 ⁇ -hydroxyvitamin D 3 derivative having a neutrophil infiltration inhibitory activity or a pharmaceutically acceptable solvate thereof.
  • a therapeutic agent for cystic fibrosis pulmonary disorder comprising, as an active ingredient, a 1 ⁇ -hydroxyvitamin D 3 derivative having a neutrophil infiltration inhibitory activity or a pharmaceutically acceptable solvate thereof.
  • Cystic Fibrosis is a fatal hereditary disease common in Caucasians that mainly affects the digestive and respiratory tracts, chronic obstructive pulmonary disease, exocrine dysfunction, and abnormally high It is characterized by three signs of sweat electrolytes. Pulmonary lesions are caused by diffuse obstruction of the small airways by abnormally thick mucus secretions, followed by bronchiolitis and mucopurulent embolism of the airways. Staphylococcus aureus is initially isolated from patients' respiratory tract secretions, but S. aureus is most often isolated as the disease progresses (Merck Manual, 16th ed., CF, 19 9 2 years).
  • Drug therapy for CF lung injury is mainly aimed at preventing airway obstruction and preventing infection.
  • 3 Stimulants are used to prevent airway obstruction, mainly because they have an airway dilating effect, but their long-term effects are low. Mucolytics and oral expectorants nebulized for clearance of respiratory secretions are also widely used, but few have supported their efficacy.
  • antibiotics are used for infection protection, but they are expensive and have the troublesome problem of emergence of resistant bacteria. Steroids and protease inhibitors have been studied as other drugs, but no promising ones have been found.
  • the active vitamin D 3 derivatives the use of calcium absorption promoting work in the small intestine, bone resorption in bone, has an action such as modulating bone formation, used as a therapeutic agent for various local Shiumu metabolic disease associated with the abnormality in Have been.
  • immunomodulatory effects, cell growth inhibitory effects, and cell differentiation inducing effects have been found.
  • therapeutic agents for malignant tumors JP-A-57-149224
  • Agents for treating rheumatoid arthritis JP-A-56-26820
  • anti-allergic agents JP-A-63-077988, UK Patent No.
  • an object of the present invention is to provide a method of treating cystic fibrosis lung injury using activated vitamin D 3 derivatives having neutrophilic infiltration suppressing action without inducing hypercalcemia as an active ingredient It is.
  • Another object of the present invention comprise an active vitamin D 3 derivatives having a depressive for production neutrophil infiltration without inducing hypercalcemia as an active ingredient, to provide a therapeutic agent for cystic fibrosis lung injury That is.
  • R 2 is the same or different and represents a hydrogen atom, a tri (C i C -alkyl ') silyl group, an acetyl group, a methoxymethyl group, or a tetrahydropyranyl group.
  • R 3 and R 4 are the same or different and are a hydrogen atom; a hydroxyl group; a C 2 -C 8 acyloxy group; an alkyloxy group;
  • R 5 , R 6 , R 7 , and R 8 are the same or different, and are a hydrogen atom, a hydroxyl group, and the same. Represents an alkyl group or a C 2 -C 8 alkoxy group.
  • R 9 represents a hydrogen atom, a hydroxyl group, a CLC-alkyl group, or a CiCetalkylthio group. . Is a hydrogen atom, what?
  • a and B are the same or different and each represent a hydrogen atom or a hydroxyl group, or together represent a single bond, and form a double bond with the specified single bond (hereinafter, “A and B together In other words, it represents the double bond as a whole.)
  • X and Y are taken together to represent a carbonyl group together with the carbon atom to which they are attached, or one of them is a hydrogen atom and the other is a hydroxyl group, or one of them is a hydrogen atom And the other is a C 2 -C 8 alkoxy group.
  • n represents an integer from 0 to 2
  • m represents an integer from 0 to 2.
  • Is accomplished by treatment method had use vitamin D 3 derivative or a therapeutic agent of cystic fibrosis lung disorders with agents containing a pharmaceutically acceptable solvate, or it is expressed in.
  • the configuration at the carbon atom at position 20 may be either the (S) configuration or the (R) configuration.
  • the configuration of the carbon atom can be either (S) or (R). Any of the positions may be used.
  • the configuration of the double bond may be either (E) or (Z).
  • the present invention also includes a mixture of these various stereoisomers in any ratio.
  • the alkyl group represents a linear or branched aliphatic hydrocarbon group or an aromatic hydrocarbon group.
  • the alkyloxy group means a linear or branched aliphatic hydrocarbon oxy group or an aromatic hydrocarbon oxy group.
  • the acyl group represents a linear or branched aliphatic hydrocarbon carbonyl group or an aromatic hydrocarbon radical group.
  • the acyloxy group means a linear or branched aliphatic hydrocarbon carbonyl group or an aromatic hydrocarbon carboxy group.
  • the alkylthio group refers to a linear or branched aliphatic hydrocarbon thio group or an aromatic hydrocarbon thio group.
  • Vitamin D 3 derivative represented by the above formula used in the present invention (1), and its best mode is as follows.
  • Z represents (Ia), (Ib), or (Ic). Among them, (1a) or (lb) is preferred.
  • R 2 is the same or different and a hydrogen atom, tri
  • (C i -C 7 alkyl) represents a silyl group, an acetyl group, a methoxymethyl group, or a tetrahydrovinylyl group. Of these, it is most preferred that and R 2 are both hydrogen atoms.
  • R 2 represents a tri (di-alkyl? Silyl) group
  • specific examples thereof include, for example, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl group, t-butyldiphenylsilyl group, tribenzylsilyl group, etc. Are preferred.
  • R 3 and R 4 are the same or different and each represent a hydrogen atom; a hydroxyl group; a C 2 -C 8 acyloxy group; a C 7 -C 7 alkyloxy group; a C i -C 6 alkylthio group; , A C 2 -C 8 alkoxy group or a C i -C 7 alkyloxy group. Represents an alkyl group.
  • R 3 and R 4 represent a C i -C 7 alkyloxy group
  • specific examples thereof include, for example, methoxy, ethoxy, propyloxy, and isopropyloxy.
  • Ethoxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, s-butyloxy, t-butyloxy, and benzyloxy groups are preferred, with methoxy, ethoxy and propyloxy groups being most preferred.
  • R 3 and R 4 represent a C 6 -C 6 alkylthio group
  • specific examples thereof include, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, s-butylthio, t-butylthio, pentylthio, isopentylthio.
  • neopentylthio, to cyclohexylthio, heptene Chiruchio there may be mentioned a phenylene group, a heteroarylthio group, among these, C i to C 4 alkylthio group, such as methylthio, Echiruchio, propyl Chio, isopropylthio, Puchiruchio, Isopuchiruchio, S-butylthio and t-butylthio groups are preferred, and among them, methylthio, ethylthio and propylthio groups are most preferred.
  • R 3 and R 4 represent a C 2 -C 8 acyloxy group
  • specific examples thereof include, for example, acetoxy, propionyloxy, isopropionyloxy, butyryloxy, isoptyryloxy, s-butyryloxy, valeryloxy, and isoyloxy. Valeryloxy, hexanoyloxy, heptyloxy, benzoyloxy and the like.
  • C 2 -C 4 acyloxy groups such as acetoxy, propionyloxy, isopropionyloxy, petyryloxy, isoptyryloxy, s-butylyloxy, and benzoyloxy groups are preferred.
  • R 3 is hydroxyl, C 2 - C 8 Ashiruokishi group, or C i to C 7 7 Rukiruokishi Ji ⁇ where Ji may be substituted with a group? If an alkyl group, C i C? Alkyl groups, hydroxyl group, C 2 ⁇ C 8 Ashiruokishi group, by ⁇ C 7 Arukiruokishi group, may be substituted at any position.
  • alkyl group examples include, for example, methyl, ethyl, propyl, isopropyl, n-butyl, isoptyl, s-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl Tyl, benzyl, hydroxymethyl, hydroxyxetil, hydroxypropyl pill, hydroxybutyl, hydroxypentyl, hydroxyhexyl, hydroxyheptyl, hydroxybenzyl, acetoxymethyl, propionyloxymethyl, ptyryloxymethyl, benzoyloxy Methyl, acetoxyl, propionyloxetil, petyryloxetil, benzoyloxetil, acetoxoxypropyl, propionyloxyp ⁇ Mouth pill, petyryloxypropyl, benzoyloxypropyl, me
  • R 4 As the combination of R 3, R 4 Of these, either one of R 3, R 4 is a hydroxyl group, the other is a hydroxyl group, C 2 ⁇ C 8 Ashiruokishi group, in even Shikuwaje ⁇ Ji Arukiruokishi group May be substituted An alkyl group; one of R 3 and R 4 is a hydrogen atom and the other is a hydroxyl group,
  • R 5 , R 6 , R 7 , and R 8 are the same or different and represent a hydrogen atom, a hydroxyl group, a CiC alkyl group, or a C 2 -C 8 acyloxy group. Among them, a hydrogen atom or a C 7 -C 7 alkyl group is preferred.
  • R 5 , R 6 , R 7 , and R 8 represent a C i -C 7 alkyl group, specific examples thereof include, for example, methyl, ethyl, propyl, isopropyl, n-butyl, isoptyl, s-butyl, and t-butyl.
  • N-pentyl isopentyl, neopentyl, n-hexyl, n-heptyl and benzyl groups, among which methyl, ethyl, propyl, isopropyl, n-butyl, isoptyl, s- A butyl or t-butyl group is preferred, and a methyl, ethyl or propyl group is particularly preferred.
  • R 5 , R 6 , R 7 , and R 8 represent a C 2 -C 8 acyloxy group
  • specific examples thereof include, for example, acetoxy, propionyloxy, isopropionyloxy, butyryloxy, isoptyryloxy, s-butylyloxy, Valeryloxy, Isovaleryloxy, Hexanoyloxy, Hep Tanoyloxy, benzoyloxy groups and the like can be mentioned.
  • C 2 -C 4 acyloxy groups such as acetooxy, propionyloxy, isopropionyloxy, petyriloxy, isoptyryloxy, s-butylyloxy and benzoyloxy groups are preferred.
  • R 9 represents a hydrogen atom, a hydroxyl group, a C i -C 7 alkyl group, or a C i Ce alkylthio group.
  • R 9 represents a C 7 -C 7 alkyl group
  • specific examples include methyl, ethyl, propyl, isopropyl, n-butyl, isoptyl, s-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, hexyl , Heptyl, benzyl and the like.
  • a CiCa alkyl group such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl, and t-butyl is preferable.
  • methyl, ethyl and propyl groups are most preferred.
  • R 9 represents a C i -C 6 alkylthio group
  • specific examples include, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, s-butylthio, t-butylthio, pentylthio, isopentylthio, neopentylthio, to cyclohexylthio, heptyl Chio
  • a phenylene group a heteroarylthio group, among these, C i ⁇ C 4 alkylthio, such as methylthio, Echiruchio, propyl Chio, isopropylthio, Puchiruchio, Isopuchiruchio
  • An s-butylthio or t-butylthio group is preferred, and a methylthio, ethylthio and 'propylthio group are
  • R i If There representing the C ⁇ C 7 alkyl group, and specific examples thereof include methyl For example, Echiru, propyl, isopropyl, n- butyl, Isopuchiru, s- butyl, t - hexyl pentyl, isopentyl, neopentyl, to - heptyl, n , Heptyl, benzyl group, etc. Of these, C!
  • ⁇ C 4 alkyl group such as methyl, Echiru, propyl, an isopropyl, n- butyl, Isopuchiru, s- heptyl, t one-butyl virtuous preferred, inter alia methyl, Echiru, a propyl group and also preferred have.
  • R. Is a C i -C 7 alkyloxy group specific examples of which include, for example, methoxy, ethoxy, propyloxy, isopropyloxy, Neopentyloxy, hexyloxy, heptyloxy, benzyloxy, etc.
  • C to C alkyloxy groups for example, methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isoptyloxy, s-butyloxy, and t-butyloxy groups are preferred, and methoxy, Ethoxy and propyloxy groups are most preferred.
  • a and B are the same or different and represent a hydrogen atom, a hydroxyl group, or a single bond when taken together. Of these, it is preferred that A and B are both hydrogen atoms, A is a hydroxyl group and B is a hydrogen atom, or that they form a single bond together. In particular, it is most preferred that both A and B are hydrogen atoms or that A and B together form a single bond.
  • X and Y together represent a carbonyl group together with the carbon atoms bonded together, or one of them is a hydrogen atom and the other is a hydroxyl group.
  • one represents the other a hydrogen atom is c 2 ⁇ c 8 Ashiruokishi group.
  • it is preferable that X and Y are a carbonyl group together with a carbon atom bonded together, or one of them is a hydrogen atom and the other is a hydroxyl group.
  • c 2 -C 8 acyloxy group examples include, for example, acetoxy, propionyloxy, isopropionyloxy, Examples thereof include a butylyloxy, an isoptyryloxy, an s-butylyloxy, a quinone, a 'relyloxy, an isovaleryloxy, a hexanoyloxy, a heptanyloxy, a benzoyloxy group, and the like.
  • a C 2 -C 4 acyl group for example, an acetooxy, propionyloxy, isopropionyloxy, petyryloxy, isobutylyloxy, s-butylyloxy group is preferred.
  • n represents an integer of 0 to 2. Among these, n is preferably 0 or 1.
  • m represents an integer of 0 to 2. Among them, m is preferably 0 or 1.
  • Vitamin D 3 derivatives used in the present invention can be converted to a solvate of their pharmaceutically acceptable as needed.
  • solvents include water, methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol, t-butanol, acetonitril, acetone, methyl acetyl ketone, black form, ethyl acetate, getyl ether. , T-butyl methyl ether, benzene, toluene, DMFDMSO and the like.
  • water, methanol, ethanol, propyl alcohol, isopropyl alcohol, acetonitril, acetone, methyl Rutile ketone and ethyl acetate are preferred.
  • the configuration of the carbon atom at the 20-position includes both the (S) configuration and the (R) configuration.
  • the carbon atom to which R 3 ZR 4 , R 5 ZR 6 , R 7 / R 8 , ⁇ , ⁇ , and ⁇ is bonded is an asymmetric center, the configuration of the carbon atom is the (S) configuration and
  • (R) Includes both configurations.
  • the double bond configuration includes both the (E) configuration and the (Z) configuration.
  • the subscripts are shown in normal size in the tables, such as "CH 2 " as "CH 2".
  • H carbyl group H H H, Pr H, H H, H
  • A 0H
  • B H Casolehol group H, H H, H H, H H, H
  • A 0H
  • B H Carbonyl group H, HH, Me H, HH, H
  • A 0H
  • B H Carbonyl group H, HH, Pr H, HH, H
  • A 0H
  • B H Carboxyl group H, H Me, Me H, HH, H
  • A 0H
  • B H
  • A 0H
  • B H Carbonyl group H, H Me, OAc H, H H, H
  • 0H B H Carbo H, H H, H H, Pr H, H
  • Equation (1) (1a) object No ⁇ m X R 1 l ⁇ i ⁇ * t, R R7 RR 4 n 1 singlet n, c i un
  • A H
  • B 0H carboni H, HH Me H, HH, H
  • A H
  • B 0H Carboxyl group H, HH, E t H, HH, H
  • A H
  • B 0H Carboxyl group H, HH, Pr HHH, H
  • A H
  • B 0H HH Me, Me H, HHH
  • n A H, ft Lulu u u p OA r H
  • Formula (1) Z (1 a) Compound N 0. ⁇ m A, ⁇ X, ⁇ R 1, R2 R3, R4 R5, Kb K /, R8
  • A OH
  • B : H OH, H H, H H, H H, H H, H
  • A OH
  • B : H OH, H H, H H, H H, H H, H
  • A OH
  • B : H OH, H H, H H, H H, H H, H
  • A: 0H
  • A: 0H
  • B: H OH, H H, H Me, OAc H, H H, H
  • 1736 1 1 A:: 0H, B H OH, H H, H Me, OAc H, H H, H
  • I 737 Z 1 A: 0H
  • B H OH, H H, H Me, OAc H, H H, H
  • Equation (1) (1 a) mouth 41 ⁇ 2 NO. ⁇ m A, X, Y R3, R4 K 0, 0 K / t K 0
  • A 0H
  • B H OH, H H, H H, H H, Pr H, H
  • A 0H
  • B H OH, H H, H H, H H, H H, Me
  • A 0H
  • B H OH, H H, H H, H H, H H, Et
  • A 0H
  • B H Carbonyl group H, H H, H H H
  • A 0H
  • B H Carbonyl group H, H H, H H H
  • A 0H
  • B H Carbonyl group H, H H, H H Me
  • A 0H
  • B H Carbonyl group H, H Me, Me Me H
  • A 0H
  • B H Carbonyl group H, H Me, Me Me H
  • A 0H
  • B H Carbonyl group H, H H, H H OEt
  • the production of the vitamin D 3 derivative represented by the above formula (1) is carried out, for example, by reacting an aldehyde represented by the following formula (2) with a compound represented by the following formula (3) or the following formula (4) in the presence of a base catalyst. After the reaction, if necessary, the reaction can be carried out by combining reactions such as dehydration, deprotection, reduction, and isomerization.
  • R 3 a, R 4 a is the same or different, a hydrogen atom, a hydroxyl group, protected A hydroxyl group; a C 2 -C 8 alkoxy group; a C i -C 7 alkyloxy group;
  • R 8 represents a C i -C 7 alkyl group which may be substituted by an acyloxy group or a C i -C alkyloxy group.
  • R 5a ', R 6a , R 7a , R 8a are Same or different, hydrogen atom, hydroxyl group, protected hydroxyl group,
  • R 9a represents a hydrogen atom, a hydroxyl group, a protected hydroxyl group, a C i -C 7 alkyl group, or a C i Ce T alkylthio group.
  • inorganic base catalysts such as lithium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, and sodium hydride; 1,8-diazabicycle .
  • Organic base catalysts such as pendene (DBU); and organic metal base catalysts such as lithium diisopropylamide, lithium hexamethyldisilylamide, and sodium hexamethyldisilylamide.
  • DBU pendene
  • organic metal base catalysts such as lithium diisopropylamide, lithium hexamethyldisilylamide, and sodium hexamethyldisilylamide.
  • base catalysts are used in an amount of 0.1 to 10 equivalents, preferably 0.5 to 3 equivalents, based on the starting aldehyde.
  • an additive for accelerating the reaction may be added to the reaction system as needed.
  • the aldehyde represented by the above formula (2) and the compound represented by the above formulas (3) and (4) undergo an equimolar reaction stoichiometrically. It is desirable to use one of which is easily available.
  • Examples of the organic solvent used in the aldol reaction include alcohol solvents such as methanol and ethanol; halogen solvents such as methylene chloride, chloroform, and tetrachlorocarbon; hydrocarbon solvents such as hexane and toluene; tetrahydrofuran and dioxane. Ether solvents such as N.N-dimethylformamide, acetonitrile, etc .; and mixed solvents thereof, which can be selected in consideration of the solubility and reactivity of the compound.
  • the reaction temperature generally ranges from 178 to the boiling point of the solvent.
  • the reaction time varies depending on the base catalyst used, the reaction solvent and the reaction temperature.
  • the compound represented by the above formula (3) or (4) or the compound represented by the above formula (2) is analyzed using analytical means such as thin layer chromatography. It is desirable to do this until any of the aldehydes disappears.
  • Examples of the dehydrating agent used in the dehydration reaction include acids such as potassium hydrogen sulfate, oxalic acid, P-toluenesulfonic acid, iodine, and anhydrous copper sulfate; halogenating agents such as thionyl chloride and phosphoric acid chloride; or methanesulfonyl chloride Aldol adducts (1)
  • This reduction reaction includes sodium cesium borohydride-cesium chloride, disobutylaluminum hydride (DI BAH), 9-porabicyclo [3.3.1] nonane (9-BBN), n-butyl borohydride Lithium, K—select tride, tri-i-butyl aluminum and the like can be used.
  • DI BAH disobutylaluminum hydride
  • 9-BBN 9-porabicyclo [3.3.1] nonane
  • n-butyl borohydride Lithium, K—select tride, tri-i-butyl aluminum and the like can be used.
  • One is a hydroxyl group), by epoxidizing the double bond located at the ⁇ , / 3 position of the side chain geton, reducing the ring opening of the epoxy ring, and oxidizing the secondary alcohol to obtain (1)
  • ( ⁇ (1a)
  • Vitamin represented by ⁇ is a hydrogen atom, ⁇ is a hydroxyl group / ⁇ , and ⁇ is a carbonyl group together with the carbon atoms that are linked together! It can be obtained 3 3 derivatives.

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention se rapporte à des remèdes contre les affections des poumons du type mucoviscidose, qui contiennent des dérivés de la vitamine D3 représentés par les formule générale (1), (1a), (1b), (1c), où R1 et R2 représentent chacun hydrogène, trialkylsilyle, acétyle, méthoxyméthyle ou tétrahydropyranyle; et R3 et R4 représentent chacun hydrogène, hydroxyle, acyloxy, alkyloxy, alkylthio ou alkyle éventuellement substitué; R5, R6, R7 et R8 représentent chacun hydrogène, hydroxyle, alkyle ou acyloxy; R9 représente hydrogène, hydroxyle, alkyle ou alkylthio; R10 représente hydrogène, alkyle ou alkyloxy; A et B représentent chacun hydrogène ou hydroxyle, ou alors A et B forment ensemble une liaison simple, X et Y représentent ensemble un atome d'oxygène carbonyle, ou alors soit X soit Y représente hydrogène et l'autre hydroxyle ou acyloxy; et n et m représentent chacun un nombre entier compris entre 0 et 2.
PCT/JP1999/007229 1998-12-24 1999-12-22 Remedes contre la mucoviscidose contenant des derives de la vitamine d¿3? WO2000038692A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU17986/00A AU1798600A (en) 1998-12-24 1999-12-22 Cystic fibrosis remedies containing vitamin D3 derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP10/367557 1998-12-24
JP36755798 1998-12-24

Publications (1)

Publication Number Publication Date
WO2000038692A1 true WO2000038692A1 (fr) 2000-07-06

Family

ID=18489612

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1999/007229 WO2000038692A1 (fr) 1998-12-24 1999-12-22 Remedes contre la mucoviscidose contenant des derives de la vitamine d¿3?

Country Status (2)

Country Link
AU (1) AU1798600A (fr)
WO (1) WO2000038692A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995014662A1 (fr) * 1993-11-24 1995-06-01 Wisconsin Alumni Research Foundation Composes de 26,28-methylene-1alpha,25-dihydroxyvitamine d¿2?
WO1998058909A1 (fr) * 1997-06-25 1998-12-30 Teijin Limited Derives de vitamine d3 et medicaments a base de ces derives pour le traitement des maladies respiratoires inflammatoires

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995014662A1 (fr) * 1993-11-24 1995-06-01 Wisconsin Alumni Research Foundation Composes de 26,28-methylene-1alpha,25-dihydroxyvitamine d¿2?
WO1998058909A1 (fr) * 1997-06-25 1998-12-30 Teijin Limited Derives de vitamine d3 et medicaments a base de ces derives pour le traitement des maladies respiratoires inflammatoires

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KURUTO RYOKO ET AL.: "Myeloid calcium binding proteins: Expression in the differentiated HL-60 cells and detection in sera of patients with connective tissue diseases", J. BIOCHEM.,, vol. 108, no. 4, 1990, pages 650 - 653, XP002922585 *

Also Published As

Publication number Publication date
AU1798600A (en) 2000-07-31

Similar Documents

Publication Publication Date Title
KR100676106B1 (ko) 비타민 ｄ3 유도체 및 그것을 사용하는 염증성 호흡기질환 치료제
JP3992297B2 (ja) ビタミンｄ３誘導体、およびそれを用いる炎症性呼吸器疾患治療剤
JP2003516400A (ja) ヒドロキシルスチルベンならびに新規スチルベン誘導体および類似体による抗炎症治療および乾癬治療ならびにプロテインキナーゼ阻害
DE4117512A1 (de) 2-phenylbenzo(b)furane und -thiophene, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate
JPH08319268A (ja) ビタミンｄ化合物及びこれらの化合物の製造法
HU211025B (en) Process for producing novel vitamin d analogues and pharmaceutical compositions containing the same
US5206230A (en) Fluorine-containing vitamin D3 analogues and pharmaceutical composition containing the same
HUT70511A (en) New leukotriene-b4 antagonists, process for preparing the same and pharmaceutical comns. contg. them
BG60530B2 (bg) Дехидрохолекалцифероли
JP2908566B2 (ja) ビタミンｄ誘導体の皮膚科学的使用
JP2002504537A (ja) シクロヘキサンジオール誘導体
US5278155A (en) Fluorine-containing vitamin D3 analogues and cell differentiation-inducing agent containing the same
DE3541933A1 (de) Cholecalciferolderivate
JPH06329696A (ja) ラクトン化合物及びその製造方法
US4853378A (en) Fluorine derivatives of vitamin D3 and process for producing the same
WO2000038692A1 (fr) Remedes contre la mucoviscidose contenant des derives de la vitamine d¿3?
JP4512490B2 (ja) ビタミンｄ類似体、該類似体を含んで成る組成物およびその使用
WO1997015546A1 (fr) Derives d'acide carboxylique et compositions pharmaceutiques
Izzo et al. Synthesis of potentially anti-inflammatory IPL576, 092-contignasterol and IPL576, 092-manoalide hybrids
JPH02180850A (ja) ピラニルエチル―ナフタレン誘導体
WO2006059768A1 (fr) Dérivé de 9,10-secoprégnane et médicament le contenant
DE4003854A1 (de) Seitenketten-homologe vitamin d-derivate, verfahren zu ihrer herstellung, diese derivate enthaltende pharmazeutische praeparate sowie deren verwendung als arzneimittel
JPWO2003070716A1 (ja) ビタミンｄ３誘導体およびそれを用いる治療剤
HU196744B (en) Process for producing cyclohexane alkane acids
JP2016017062A (ja) 抗癌剤

Legal Events

Date Code Title Description
ENP Entry into the national phase

Ref country code: AU

Ref document number: 2000 17986

Kind code of ref document: A

Format of ref document f/p: F

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 2000590644

Format of ref document f/p: F