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WO1996006088A1 - Derive benzothyazolesulfonamide renfermant un groupe cycloalkyle terminal et utilisation medicale de ce derive - Google Patents

Derive benzothyazolesulfonamide renfermant un groupe cycloalkyle terminal et utilisation medicale de ce derive Download PDF

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Publication number
WO1996006088A1
WO1996006088A1 PCT/JP1995/001637 JP9501637W WO9606088A1 WO 1996006088 A1 WO1996006088 A1 WO 1996006088A1 JP 9501637 W JP9501637 W JP 9501637W WO 9606088 A1 WO9606088 A1 WO 9606088A1
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Prior art keywords
carbon atoms
alkyl group
group
unsubstituted
substituted
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PCT/JP1995/001637
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English (en)
Japanese (ja)
Inventor
Takeshi Tonegawa
Yoshihide Nozaki
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Asahi Kasei Kogyo Kabushiki Kaisha
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Publication of WO1996006088A1 publication Critical patent/WO1996006088A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2

Definitions

  • the present invention relates to a novel benzothiazolsulfonamide derivative and a pharmaceutical use thereof. More specifically, the present invention relates to a novel benzothiazole having a terminal cycloalkyl group having an N-substituted sulfonamide group, wherein the substituent group has a cycloalkyl group at its terminal. The present invention relates to a sulfonamide derivative and a medicinal use thereof.
  • the benzothiazo-norresulfonamide derivative having a terminal alkyl group of the present invention and a pharmaceutically acceptable acid addition salt thereof have a strong tracheal smooth muscle relaxing action, and are therefore used as bronchodilators or asthma preventive / therapeutic agents.
  • the IgE antibody As an active ingredient of a pharmaceutical composition which is an agent for treating and / or preventing diseases caused by abnormally elevated levels (hereinafter, often simply referred to as “abnormalities”), particularly allergic diseases including bronchial asthma. Useful.
  • bronchodilators such as xanthine drugs and / 3 receptor stimulants are used as clinical treatments for respiratory diseases such as asthma. These drugs are thought to increase the concentration of cyclic adenosine 3,5'-monophosphate (cAMP) in cells.
  • cAMP cyclic adenosine 3,5'-monophosphate
  • Aminofilin is a typical example of a xanthine drug
  • isoprenetenol is a typical example of a receptor stimulant.
  • xanthine drugs and / or /? Receptor stimulants have various side effects on the heart, etc., as well as the emergence of resistant asthma, which does not relieve with these drugs. It did not satisfy the medical needs.
  • WO92-147172 (corresponding to EP Publication No. 0 525 203) discloses that benzothiazolesulfonyl having tracheal smooth muscle relaxing action based on antihistamine action Aminoethyl derivative, specifically, compound (20) as 1- (6-benzothiazolesnolephonylaminoethyl) 141- [3- (phenoxy) propyl] pi Perazine, that is, 1- [2- (6-benzothiazolsnorrehonylamino) ethyl] 1-41- (3-phenoxypropyl) piperazine, is disclosed, but its action is Not enough yet.
  • diseases caused by excessive production of IgE antibodies include atopic asthma, atopic dermatitis, and nasal allele.
  • Allergic diseases such as giants are known.
  • the treatment of allergic monogenic disease involves methods of inhibiting mast cell or basophil degranulation and release of chemical mediators, and antagonizing the allergic response triggered by Z or released chemical mediators. Only symptomatic treatment, such as a method of suppressing it by reaction, was performed. These palliative treatments did not suppress the excessive production of IgE antibody, which is the basis of the allergic reaction, and their effects were limited.
  • a novel compound that has not only a strong tracheal smooth muscle relaxing action but also a strong IgE antibody production inhibitory action, particularly from the viewpoint of treatment of atopic asthma. It is also desirable from the viewpoint of the treatment of bronchoconstriction other than atopic asthma and diseases caused by abnormal IgE antibody levels.
  • the present inventors have synthesized various compounds and have conducted intensive studies on their pharmacological actions.
  • the novel benzothiazolsulfonamide derivative having a terminal alkyl group represented by the formula (I) which is a new compound, has a conventional terminal alkyl group.
  • No benzo In addition to having a tracheal smooth muscle relaxing action equal to or greater than that of the thiazolesulfonamide derivative, the conventional benzothiazole snolefonamide derivative without a terminal alkyl group did not have I
  • the present inventors have also found that they have a gE antibody production inhibitory action, and completed the present invention.
  • one object of the present invention is to provide a novel compound having a strong tracheal smooth muscle relaxing action and an IgE antibody production inhibitory action.
  • Another object of the present invention is to provide a medicament containing the above compound, which is useful as a therapeutic / prophylactic agent for asthma, a bronchodilator or a therapeutic / prophylactic agent for diseases caused by abnormal levels of IgE antibodies.
  • a medicament containing the above compound which is useful as a therapeutic / prophylactic agent for asthma, a bronchodilator or a therapeutic / prophylactic agent for diseases caused by abnormal levels of IgE antibodies.
  • Still another object of the present invention is to provide a method for treating asthma, which comprises administering the above pharmaceutical composition to an asthmatic patient.
  • Yet another object of the present invention is to provide a method for treating bronchoconstriction, which comprises administering the above pharmaceutical composition to a patient having bronchoconstriction.
  • Yet another object of the present invention is to provide a method for treating an abnormal IgE antibody level, comprising administering the above pharmaceutical composition to a patient suffering from an abnormal IgE antibody level. It is intended to provide a method for treating the diseases that occur.
  • A represents an unsubstituted or alkylene group having 2 to 6 carbon atoms, which is substituted with an alkyl group having 4 carbon atoms;
  • B represents an unsubstituted or 1 alkylene group;
  • R 1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms
  • R 2 and R 3 each independently represent a hydrogen atom or a carbon atom; or shows a 6 alkyl group, or, R 2 and R 3 taken together, form an unsubstituted or C 4 alkylene group having a carbon substituted with number 4 alkyl group having a carbon
  • R 4 Is unsubstituted or substituted by an alkyl group having 14 carbon atoms.
  • the benzothiazole sulfonamide derivative having a terminal cycloalkyl group of the present invention has an N_-substituted sulfonamide group, and the substituent has It is characterized by containing a cycloalkyl group at the terminal.
  • A represents an alkylene group having 2 to 6 carbon atoms which is unsubstituted or substituted by an alkyl group having 1 to 4 carbon atoms.
  • alkylene group having 2 to 6 carbon atoms include an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group, and a hexamethylene group.
  • Limethylene groups are particularly preferred.
  • This alkylene group is an alkyl group having 1 to 4 carbon atoms at any of its substitution positions, for example, methyl, ethyl, propyl, isopropynole, butylisobutyl, 1-methylpropyl, t-butyl.
  • a methyl group is particularly preferred.
  • a 3- (7-benzothiazolesulfoninole) -14-cyclohexynolemethinole——3-methylinyl group substituted at the 3-position with a methyl group —— 1,4-Diazabutane is preferred.
  • B is an alkylene group having 1 to 6 carbon atoms which is unsubstituted or substituted by an alkyl group having 1 to 4 carbon atoms. Or-or a single bond.
  • alkylene group having 1 to 6 carbon atoms include a methylene group, an ethylene group, a trimethylene tetramethylene group, a pentamethylene group, and a hexamethylene group. Groups and ethylene groups are particularly preferred.
  • the alkylene group is an alkyl group having 1 to 4 carbon atoms at any of its substitution positions, for example, methyl, ethyl, propyl isopropyl, butyl, isobutynole, 1-methyl propylene, t It may be substituted with a monobutyl group or the like. As a substituent, a methyl group is particularly preferred. It is also preferred that B is a single bond.
  • R 1 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • alkyl group having 1 to 4 carbon atoms include methyl, ethyl, propyl, isopropyl, butyl, isobutynole, 1-methylopenyl pill, and t-butyl group. And a methyl group is particularly preferred. It is also particularly preferred that R 1 is a hydrogen atom.
  • R 2 and R 3 each independently represent a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or R 2 and R 3 together form unsubstituted or 1 to 4 carbon atoms. It forms an alkylene group having 1 to 4 carbon atoms, which is substituted with a plurality of alkyl groups.
  • R 2 and R 3 each independently represent an alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl isopropyl, butyl, isobutyl, 1-methyl propylene, Examples thereof include t-butyl, pentyl, and hexyl groups, and methyl, ethyl and propyl groups are particularly preferred. It is particularly preferable that R 2 and R 3 are each a hydrogen atom.
  • alkylene group having 1 to 4 carbon atoms formed by R 2 and R 3 together examples include a methylene, ethylene, trimethylene, and tetramethylene group. , Ethylene, and trimethylene groups are particularly preferred.
  • the alkylene group is an alkyl group having 1 to 4 carbon atoms at any of the substitution positions, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 1-methylpropyl, It may be substituted with a t-butyl group or the like.
  • a substituent a methyl group or an ethyl group is particularly preferred.
  • R 4 represents an unsubstituted group or a cycloalkyl group having 3 to 7 carbon atoms which is substituted with an alkyl group having 1 to 4 carbon atoms.
  • the cycloalkyl group include cyclopropynole, cycloprop "tinole, cyclopentinole, cyclohexinole, and cyclohexyl, and cyclobutyl, cyclopentyl, and cyclohexyl groups.
  • a cycloalkyl group is an alkyl group having 1 to 4 carbon atoms at any of its substitution positions, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and 1-methylpropyl. It may be substituted by pill, t-butyl group, etc.
  • a methyl group is particularly preferred.
  • an alkyl group represented by R 1 , R 2 and R 3 and an alkyl group as a substituent in A, B, R 2 , R 3 and R 4 are respectively It may be linear or branched.
  • A represents an unsubstituted or substituted methylene or trimethylene group
  • B represents a methylene or ethylene group, or represents a single bond.
  • R 1 represents a hydrogen atom or a methyl group
  • R 2 and R 3 each represent a hydrogen atom
  • R 4 represents a cycloalkyl group having 3 to 7 carbon atoms;
  • R 2 R 3 It is preferably bonded to the 6- or 7-position of the benzothiazole ring.
  • A represents an ethylene group or a trimethylene group which is unsubstituted or substituted with a methyl group
  • B represents a methylene group or an ethylene group.
  • R 1 represents a hydrogen atom
  • R 2 and R 3 represent R 4 represents a cycloalkyl group having 3 to 7 carbon atoms
  • R 4 represents a cycloalkyl group having 3 to 7 carbon atoms, and in the formula (I), 2 N— A— N— B— R 4
  • R 2 R 3 is bonded to position 6 or 7 of the benzothiazole ring.
  • Compound (I) of the present invention can be produced by various methods.
  • compound (I) has the formula ( ⁇ )
  • amine ( ⁇ ) is a method known per se, for example, Experimental Chemistry Lecture, 4th edition, Vol. 20, page 28 (issued by Nihon Kuni Maruzen Co., Ltd., 1992); Synthes is (1975) 135-146 Tet rahedron Letters, 29 (50), 6651-6654 (1988) and Journal of Organic Chemist, 58 (14), 3736.
  • the compound can be synthesized according to the method described in -3741 (1993).
  • the compound ( ⁇ ) has the formula (IV)
  • Sulfonic acid (IV) can be prepared by a method known per se, for example, Bull. Soc. Chim.
  • Examples of the inert solvent used in the reaction between the compound (III) and the amide (III) include halogenated hydrocarbons such as dichloromethane and cross-linked form, and tetrahydrofuran. Ethers such as lahydrofuran, dioxane, and diethyl ether; dimethyl sulfoxide; N
  • the amount of the inert solvent to be used is 100 times, preferably 5 to 50 times, the weight ratio of the compound ( ⁇ ).
  • Acid acceptors include, for example, sodium hydrogen carbonate, sodium hydroxide, potassium carbonate, sodium carbonate, potassium hydroxide, sodium methylate, and the like.
  • Organic tertiary amines such as metal compounds, pyridine, trimethylamine, and triethylamine.
  • the amount of the acid acceptor to be used is 0.3 to 10 moles, preferably 1 to 3 moles, relative to compound (III).
  • the amount of the amine (m) to be reacted with the compound ( ⁇ ) is 1 to 20 times, and preferably 1 to 10 times, the mole of the compound ( ⁇ ). It is particularly preferred that the molar ratio is 2.5 to 5 times in the absence of an acid receptor, and it is particularly preferable that the amount is 1 to 3 times in the presence of an acid acceptor.
  • the reaction temperature is generally from 130 to 120 ° C, preferably from 120 to 50 ° C.
  • the reaction time is generally 0.5 to 48 hours, preferably 0.5 to 6 hours, but thin-layer chromatography (TLC), high-speed liquid chromatography. The progress of the reaction may be monitored by chromatography (HPLC) or the like to confirm the disappearance of the compound (II), and the reaction may be terminated as appropriate.
  • compound (I) can be obtained in a free base state as follows.
  • the reaction solvent is a hydrophilic solvent
  • the solvent is distilled off from the reaction mixture, the resulting residue is dissolved in a non-hydrophilic solvent, and the residue is washed with a weak aqueous solution of alkali, water, and the like.
  • the reaction solvent is a non-hydrophilic solvent
  • the reaction mixture is directly washed with a weak aqueous alkali solution, water, or the like, and the non-hydrophilic solvent is distilled off to remove the compound ( I) can be obtained.
  • the compound (I) of the present invention is preferably in the form of an acid addition salt by a known method.
  • compound (I) is dissolved in alcohols such as methanol and ethanol, and an acid is added in an equivalent to several times the amount to obtain an acid addition salt thereof. Can be done.
  • a pharmaceutically acceptable acid addition salt is preferable.
  • the acid used include inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, and sulfuric acid, acetic acid, citric acid, tartaric acid, sulfuric acid, conodic acid, fumanoleic acid, maleic acid, and metaphoric acid.
  • Organic acids such as acetic acid, guesoleamic acid and aspartic acid can be mentioned as typical examples, but other known acids can also be used.
  • the above-mentioned acid addition salt can be used, for example, in Experimental Chemistry Course, 4th Edition, Vol. 20, pp. 284 (Maruzen, Japan) (Published by Co., Ltd., 1992)) to recycle compound (I) by realizing the compound by a known method. It can also be obtained in the state of a released base.
  • the compound (I) of the present invention or a pharmaceutically acceptable acid addition salt thereof (hereinafter, often referred to as “the compound of the present invention”) not only exhibits a strong tracheal smooth muscle relaxing action, but also a strong IgE. Has production for antibody production suppression. In addition, no death was observed when the compound of the present invention was orally administered to rats at 300 mg / kg. Therefore, the compound of the present invention is useful, active, and safe as an active ingredient of a pharmaceutical composition.
  • a pharmaceutical composition comprising a therapeutically effective amount of a compound of the present invention, and at least one pharmaceutically acceptable carrier.
  • Typical uses of the pharmaceutical composition of the present invention include asthma preventive / therapeutic agents, bronchodilators, and preventive / therapeutic agents for diseases caused by abnormal IgE antibody levels.
  • Examples of the dosage form for preparing the pharmaceutical composition of the present invention include tablet powders, granules, syrups, suppositories, suspensions, capsules, injections, inhalants, and the like.
  • various pharmaceutically acceptable carriers are used according to these preparations.
  • Tablets, powders, granules, syrups, suppositories, suspensions include excipients such as lactose, sucrose, glucose, starch, and crystalline cellulose; hydroxypropinoresenolose, dexamethasyl cellulose, and starch.
  • Binders such as gum arabic, gelatin, gelatin, glucose, sucrose, tragacanth, sodium anoregate; disintegrators such as carboxymethylcellulose, starch, calcium carbonate; stearic acid, Lubricants such as refined talc, sucrose fatty acid ester, hydrogenated vegetable oil, magnesium stearate, calcium stearate; sodium lauryl sulfate, soy lecithin, sucrose fatty acid ester, Surfactants such as polysorbate 80; additives such as lecithin and soybean oil glycerin; fluidity enhancers; and coloring agents.
  • disintegrators such as carboxymethylcellulose, starch, calcium carbonate
  • Lubricants such as refined talc, sucrose fatty acid ester, hydrogenated vegetable oil, magnesium stearate, calcium stearate; sodium lauryl sulfate, soy lecithin, sucrose fatty acid ester, Surfactants such as polysorbate 80; additives such as lecithin and soybean oil
  • diluents such as distilled water for injection, physiological saline, aqueous solution of glucose, vegetable oil for injection, propylene glycol, and polyethylene glycol are generally used. Can be used. If desired, bactericides, preservatives, stabilizers, tonicity agents, soothing agents and the like may be added. ⁇ Also, in the preparation of inhalants, polychloromonofluoromethan Etc. can be used as a solvent.
  • a method for treating asthma comprising administering to a patient with asthma a therapeutically effective amount of the compound of the present invention.
  • a therapeutically effective amount of the present invention comprising administering a light compound to a patient having bronchoconstriction.
  • an abnormal IgE antibody level comprises administering a therapeutically effective amount of a compound of the present invention to a patient suffering from an abnormal IgE antibody level.
  • the compound of the present invention When the compound of the present invention is administered to humans, it can be orally administered in the form of tablets, powders, granules, syrups, suppositories, suspensions, and capsules as described above. It can be administered parenterally, by injection, including infusion, or in the form of a cream or spray.
  • the dosage varies depending on the indication, dosage form, patient age, body weight, and the degree of symptoms. In general, 3 to 300 mg per day for an adult is administered in 1 to 3 divided doses.
  • the daily administration period is generally several B to 2 months, but the daily dose and administration period can be reduced depending on the patient's symptoms.
  • Example 1 In Example 1, 28.2 g of 1-cyclohexylmethyl-1,2-methyl-1,4-diazabutane 28.2 g was used instead of N-cyclohexylmethyl-ethylenediamine 26.1 g.
  • the title compound 6 was obtained in substantially the same manner as in Example 1 except for using it ( yield: 10.2 g (yield: 50%)
  • Example 1 N-cyclohexylmethyl-ethylene was used.
  • the title compound was prepared in substantially the same manner as in Example 1 except that N—2—cyclohexylethyl-ethylenediamine 28.2 g was used instead of diamine 26.1 g. I got 8. Yield 9.4 g (Yield 46%)
  • the title compound was prepared in substantially the same manner as in Example 1 except that 12 g of 6-benzothiazolesulfonic acid was used instead of 12 g of 7-benzothiazolesulfonic acid.
  • Example 1 is the same as Example 1 except that 23.8 g of N-cyclopentylmethylethylethylenediamine was used instead of 26.1 g of N-cyclohexylmethylethylethylenediamine. And real / 06
  • Example 1 was repeated except that 19.1 g of N-cyclopropylmethylethylethylenediamine was used in place of 26.1 g of N-cyclohexylmethylethylethylenediamine in Example 1. In substantially the same manner, the title compound 3 was obtained. Yield 8.8 g (Yield 51%)
  • Example 1 is the same as Example 1 except that N-cyclohexylmethyl-ethylenediamine 26.1 g was replaced with N-cycloheptylmethyl-ethylenediamine 28.4 g. In substantially the same manner as described above, the title compound 4 was obtained. Yield 11.4 g (Yield 56%)
  • Example 1 was repeated except that 26.1 g of N-cyclohexylmethyl-ethylenediamine was used in place of 26.1 g of N-cyclohexylmethyl-ethylenediamine. In substantially the same manner as in Example 1, the title compound 5 was obtained. Yield 9.7 g (Yield 47%)
  • Example 1 is the same as Example 1 except that 23.8 g of N-cyclohexylmethylethylenediamine was used in place of 26.1 g of N-cyclohexylmethylethylethylenediamine. In substantially the same manner, the title compound 7 was obtained. Yield 9.9 g (52% yield) The obtained hydrochloride of compound 7 was obtained in the same manner as in Example 1. Yield 9.7 g (Yield 8.8%)
  • Example 1 is substantially the same as Example 1 except that 32.8 g of 4-cyclohexylmethyl ylhomopiperazine is used in place of 26.1 g of N-cyclohexylmethylethylethylenediamine in Example 1. In a similar manner, the title compound 9 was obtained. Yield 12.9 g (yield 59%)
  • Example 1 was repeated except that 21.4 g of N-cyclopentynoleethylenediamine was used in place of 26.1 g of N-cyclohexylmethylethylethylenediamine. In substantially the same manner, the title compound 11 was obtained. Yield 10.2 g (Yield 56%)
  • Example 1 N-cyclohexylmethylethylenediamine (26.1 g) was replaced with 1-cyclopropylmethyl-2-1-2-methyl-1,4-diazabutane (21.4 g).
  • the title compound 12 was obtained in substantially the same manner as in Example 1 except that was used. Yield 9.9 g (54% yield)
  • Example 1 is the same as Example 1 except that 21.4 g of N-cyclobutylmethylethylethylenediamine was used in place of 26.1 g of N-cyclohexylmethylethylethylenediamine. In substantially the same manner as 1, the title compound 13 was obtained. Yield 10.5 g (Yield 58%)
  • Example 2 Substantially the same method as in Example 1 except that 12.8 g of 2-methyl-7-benzothiazolesulfonate was used instead of 12 g of 7-benzothiazolesulfonate in Example 1. Afforded the title compound 14. Yield 11 g (54% yield)
  • the compound (I) of the present invention or a pharmacologically acceptable acid addition salt thereof has a tracheal smooth muscle relaxing action on KC 1 contraction in a guinea pig isolated tracheal specimen. It is especially useful as a treatment and prevention agent for asthma.
  • the spleen was excised, and the spleen cells obtained by crushing and a suspension were prepared in Cick's MEM medium (Irvine scie- mentific, USA).
  • the IgE antibody production of the compound of the present invention was measured according to the method described in Immunology, 15, 47-54, (1988). That is, the IgE antibody in the supernatant was added to the optimal concentration of rat anti-mouse IgE monoclonal antibody (2 ⁇ g / ml), biotin-labeled rat anti-mouse Ig E antibody was quantified by an enzyme immunoassay using a monoclonal antibody (2 ⁇ g / m 1) and avidin peroxidase (2.5 ug / ml) (Funakoshi, Japan). Two types of rat anti-mouse IgE monoclonal antibodies
  • Control product (1) 1 [2-(6-Benzothiazolsulfoninorea mino) ethyl]-4-(3-phenoxypropyl) piperazine dihydrochloride
  • Control product (2) N — [2— (3, 4—Methylene benzyloxyamino) ethyl] — 7—Venzothia azole sulfonamide
  • the compound (I) of the present invention or a pharmaceutically acceptable acid addition salt thereof has an inhibitory action on IgE antibody production, it prevents and treats diseases caused by abnormal IgE levels. It is useful as an active ingredient of an agent, particularly an agent for treating and preventing atby asthma.
  • the benzothiazolsulfonamide derivative having a terminal cycloalkyl group of the present invention represented by the formula (I) and the acid addition salt thereof are the conventional benzothiazolsulfonamides having no terminal cycloalkyl group. Not only has a tracheal smooth muscle relaxing activity equal to or greater than that of benzothiazole sulfonamide derivatives, but also becomes a conventional benzothiazole sulfonamide derivative without a terminal cycloalkyl group, and IgE antibody production It also has an inhibitory effect.
  • the benzothiazolsulfonamide derivative having a cycloalkyl group of the present invention and the pharmaceutically acceptable acid addition salt thereof can be used as a therapeutic / prophylactic agent for asthma, a bronchodilator or an IgE antibody. It is useful as an active ingredient of a pharmaceutical composition that is an agent for treating and preventing diseases caused by abnormal levels.

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Dérivé benzothyazolesulfonamide renfermant un groupe cycloalkyl terminal, représenté par la formule générale (I), ou sel acide d'addition pharmaceutiquement acceptable de ce dérivé. Dans cette formule A représente un groupe C2-C6 alkylène qui est non substitué ou substitué par un groupe C1-C4 alkyl; P représente soit un groupe C1-C6 alkylène qui est non substitué ou substitué à un groupe C1-C4 alkyl, ou une liaison unique; R1 représente l'hydrogène ou un groupe C¿1?-C4 alkyl; R?2 et R3¿ représentent indépendamment l'un de l'autre l'hydrogène ou un groupe C¿1?-C6 alkyl, ou bien ils sont combinés ensemble pour former un groupe C1-C4 alkyl qui est non substitué ou substitué par un groupe C1-C4 alkyl; et R?4¿ représente un groupe C¿3?-C7 cycloalkyl qui est non substitué ou substitué par un groupe C1-C4 alkyl. Ces composés se révèlent utiles comme principe actif d'un médicament curatif ou préventif de l'asthme, de bronchodilatateur, ou d'une composition médicale destinée au traitement ou à la prévention des maladies résultant d'un niveau anormal d'anticorps IgE.
PCT/JP1995/001637 1994-08-18 1995-08-18 Derive benzothyazolesulfonamide renfermant un groupe cycloalkyle terminal et utilisation medicale de ce derive WO1996006088A1 (fr)

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JP19393394 1994-08-18

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992014712A1 (fr) * 1991-02-13 1992-09-03 Asahi Kasei Kogyo Kabushiki Kaisha Derive de sulfonamide substitue ou composition pharmaceutique contenant ce derive
WO1994019336A1 (fr) * 1993-02-19 1994-09-01 Asahi Kasei Kogyo Kabushiki Kaisha Derive de benzothiazolesulfonamide, procede de production et application de ce derive

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992014712A1 (fr) * 1991-02-13 1992-09-03 Asahi Kasei Kogyo Kabushiki Kaisha Derive de sulfonamide substitue ou composition pharmaceutique contenant ce derive
WO1994019336A1 (fr) * 1993-02-19 1994-09-01 Asahi Kasei Kogyo Kabushiki Kaisha Derive de benzothiazolesulfonamide, procede de production et application de ce derive

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