IL43761A - 1-(4-cyano-phenoxy)-2-hydroxy-3-(2-(5-1h-tetrazolyl)-chromon-5-yloxy)-propane and salts thereof their preparation and pharmaceutical compositions containing them - Google Patents
1-(4-cyano-phenoxy)-2-hydroxy-3-(2-(5-1h-tetrazolyl)-chromon-5-yloxy)-propane and salts thereof their preparation and pharmaceutical compositions containing themInfo
- Publication number
- IL43761A IL43761A IL43761A IL4376173A IL43761A IL 43761 A IL43761 A IL 43761A IL 43761 A IL43761 A IL 43761A IL 4376173 A IL4376173 A IL 4376173A IL 43761 A IL43761 A IL 43761A
- Authority
- IL
- Israel
- Prior art keywords
- chromon
- tetrazolyl
- yloxy
- propane
- hydroxy
- Prior art date
Links
- 150000003839 salts Chemical class 0.000 title claims description 13
- AQMBNKMVOOFSOJ-UHFFFAOYSA-N 4-[2-hydroxy-3-[4-oxo-2-(2h-tetrazol-5-yl)chromen-5-yl]oxypropoxy]benzonitrile Chemical compound C=1C=CC=2OC(C3=NNN=N3)=CC(=O)C=2C=1OCC(O)COC1=CC=C(C#N)C=C1 AQMBNKMVOOFSOJ-UHFFFAOYSA-N 0.000 title claims 2
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- -1 4-cyano-phenoxy Chemical group 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 235000019270 ammonium chloride Nutrition 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 229960002052 salbutamol Drugs 0.000 claims description 2
- 239000001294 propane Substances 0.000 claims 8
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 6
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims 2
- HQARDVLSJLCFBA-UHFFFAOYSA-N 4-[(4-aminophenyl)carbamoyl]-1h-imidazole-5-carboxylic acid Chemical compound C1=CC(N)=CC=C1NC(=O)C1=C(C(O)=O)NC=N1 HQARDVLSJLCFBA-UHFFFAOYSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 claims 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 229960002657 orciprenaline Drugs 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 claims 1
- 239000007787 solid Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000024780 Urticaria Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 240000006413 Prunus persica var. persica Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000003182 bronchodilatating effect Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical compound [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002071 phenylalkoxy group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/24—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 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 in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
Description
This invention relates to pharmacologically active compounds useful in the treatment of allergic and matory particularly allergic asthma and hay Belgian Patent issued on May provides for compounds having the formula 1 2 3 4 7 in each of R R R R R and R can be phenyl alkoxy or alkyl with the condition that one or 1 2 3 7 more of group R R R and R is other than hydrogen or X is a hydrocarbon chain of from 2 to 4 carbon optionally substituted by and E is a carboxy or tetrazolyl This invention relates to and its pharmacologically a process for preparing that and compositions for the treatment of asthma comprising and its has the Pharmacologically salts of for the and hydroxymethylaminomethane Compound I is prepared by the following reacting in which R is an alkyl group of from 1 to 4 carbon with ammonia in a solvent such as or a at from to to obtain the corresponding CN dehydrating the amide at a temperature of from to with a reagent mixture such as fonyl or toluenesulfonyl in dimethyl formamide to obtain the corresponding reacting the nitrile with sodium azide and ammonium or sodium chloride in an organic solvent such as or dimethylacetamide to obtain a corresponding salt of a tetrazolyl wherein X is a or ammonium treating the tetrazolyl derivative with a dilute mineral acid to acidify the salt and to hydrolyze the group thereof to obtain compound Step of the process optionally may be carried out with an azide such as or lithium azide without ammonium or sodium in that in VIII is a or lithium Starting materials V are prepared as reacting 2 with in in the presence of benzyltrimethylanunonium hydroxide to obtain a recovering the and reacting it with diethyl oxalate to obtain an recovering the and reacting it with cyclization mixture such as concentrated hydrochloric i acid and a lower alcohol of 1 to 4 carbon thus compound Details of the preceding synthesis are available in Patent and are key intermediates in the synthesis of compound Compound I its salts possess properties that make them useful in treating and certain inflammatory those pounds may also be useful in treating autoimmune An effect is produced in an individual in need of such therapy by administration of an effective amount of compound I or a pharmacologically acceptable salt The term means a human being or an experimental animal used as a model The compounds may be administered by or other suitable routes of Effective doses range1 from to Succeeding example 5 provides details of the Compound I and its salts also have activity upon topical application to inflammed areas of the skin or of the For the treatment of compound I or a salt thereof may be in a form suitable for administration by That form can comprise a suspension or solution of the active ingredient in water or in a suitable alcohol for administration as an by means of a conventional that can comprise a sion or solution of the active ingredient in a conventional liquefied propellant to be administered as an aerosol from a pressurized The forms for administration can comprise the solid active ingredient in a solid diluent for administration from a powder inhalation Other routes of oral or buccal rectal parenteral or i intravenous can also be The form for administration can also in tion to compound X other active bronchodilating those of the such as or prenaline or The forms for administration can contain to by weight of compound or a salt If salbutamol or or sulphate are they are suitably present in a concentration of to by Example 1 2 in chloroform and ethanol were cooled at and saturated with The precipitated solid was washed with ethanol and dried to as a cream C H N C H N Example 2 1 2 5 FORMATE 1 and toluenesulphonyl chloride in pyridine and dimethylformamide were heated under reflux at with stirring for 90 then poured into water and acidified with The brown precipitate which formed was and washed with hot ethanol to as a pink formate C H N C H N Example 1 2 1 formate sodium azide ammonium chloride and dimethylformamide cooling and filtering solid the solution was poured into water and acidified to pH 1 with dilute hydrochloric acid and heated for one hour at The suspension was filtered to give a yellow solid which after crystallization from cream prisms of 2 5 C H N C H N Example SODIUM 1 3 2 was dissolved with warming in a solution of sodium hydrogen carbonate in water The resulting solution was filtered and to give a pale peach This was solved in ethanol and on standing a solid was This was filtered and dried to yield sodium 2 as white C Η N C Η N Example 5 ACTIVITY Compounds described in above examples 3 and 4 were evaluated for activity in the rat by the passive cutaneous anaphylaxis test utilizing egg albumin as the PCA is an experimentally allergic reaction which develops in the skin of test animals after venous injection of an The intensity of such PCA reactions is assessed by measuring the diameters of wheals which develop in the skin of the test Details of the PCA test can be found in the following 465 113 In the following ID50 is the dose which reduced the diameter of the wheal by in ected intravenously together with the LD50 is the intravenous dose that caused death in of the test Therapeutic index is the The reference compounds utilized disodium chromoglycate and sodium TABLE CED COM insufficientOCRQuality
Claims (7)
1. A compound selected from the group consisting of 1- (4-cyano-phenoxy) -2-hydroxy-3- [2- (5-lff-tetrazolyl) - chromon-5-yloxy] -propane or a pharmacologically acceptable, non-toxic salt thereof.
2. The compound as in claim 1, 1- (4-cyano-phenoxy) - 2-hydroxy-3- [2- (5-l#-tetrazolyl) -chromon-5-yloxy] -propane.
3. The compound as in claim 1, sodium 1- (4-cyano-phenox) 2-hydroxy-3- [2- (5-li7-tetrazolyl) -chromon-5-yloxy) -propane .
4. A process for preparing 1- (4-cyano-phenoxy) -2- (hydroxy) -3- [2- (5-lff-tetrazolyl) -chromon-5-yloxy] -propane , which process comprises: reacting a compound having the formula wherein R is an alkyl · group of 1 to 4 carbon atoms, with . ammonia in a solvent selected from the group consisting of ethanol, chloroform, methanol, and a chloroform/methanol mixture to obtain an amide, 1- (4-cyano-phenoxy) -2-hydroxy-3- (2- carbamoyl-chromon-5-ylox )-propane, dehydrating the amide with a reagent selected'^rom the v group consisting of p-toluenesulfonyl chloride/pyridine , p-toluenesulfonyl chloride/lutidine , and p-toluenesulfonyl chloride/collidine in dimethylformamide, to obtain the corresponding nitrile formate, 1- (4-cyano-phenoxy) -2-formy- loxy) -3- (2-cyano-chromon-5-yloxy) -propane ; reacting the nitrile with sodium azide and ammonium chloride or lithium chloride in the presence of a second solvent selected from the group consisting of dimethylformamide, dimethylsulfoxide, and dimethylacetamide, to obtain a corresponding tetrazolyl salt selected from the group consisting of sodium, lithium, potassium, or ammonium 1- (4-cyano-phenoxy) - 2-hydroxy-3- [2- (5-l#-tetrazolyl) -chromon-5-yloxy] -propane formate; and acidifying the tetrazolyl salt with a dilute mineral acid to obtain the 1- (4-cyano-phenoxy) -2-hydroxy-3- [2- (5-lff-tetrazolyl) -chromon- 5-yloxy] -propane .
5. A composition for the treatment of asthma comprising: from 0.1% to 10% by weight of 1- (4-cyanophenoxy) -2-hydroxy- 3- [2- (5-1H- etrazolyl) chromon-5-yloxy]propane or a pharmacologically acceptable salt thereof and from 0.1 to 5% by weight of salbutamol in a pharmaceutically acceptable vehicle.
6. A composition for the treatment of asthma comprising: from 0.1% to 10% by weight of 1- (4-cyanophenoxy) -2-hydroxy- 3- [2- (5-lH-tetrazolyl) chromon-5-yloxy]propane or a pharmacologically acceptable salt thereof and from 0.1% to 5% by weight of isoprenaline sulfate in a pharmaceutically acceptable vehicle.
7. A composition for the treatment of asthma comprisings from 0.1% to 10% by weight of 1- (4-cyanophenoxy)-2-hydroxy-3- 12- (5-lH-tetrazolyl) chromon-5-yloxy] ropane or a pharmacologically acceptable salt thereof and from 0.1% to 5% by weight of orciprenaline sulfate in a pharmaceutically acceptable vehicle.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB5611772A GB1457254A (en) | 1972-12-05 | 1972-12-05 | 1-phenoxy-2-hydroxy-3-chromonyloxy-propane derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL43761A0 IL43761A0 (en) | 1974-03-14 |
| IL43761A true IL43761A (en) | 1977-10-31 |
Family
ID=10475767
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL43761A IL43761A (en) | 1972-12-05 | 1973-12-05 | 1-(4-cyano-phenoxy)-2-hydroxy-3-(2-(5-1h-tetrazolyl)-chromon-5-yloxy)-propane and salts thereof their preparation and pharmaceutical compositions containing them |
Country Status (16)
| Country | Link |
|---|---|
| JP (2) | JPS533392B2 (en) |
| AR (1) | AR199426A1 (en) |
| AU (1) | AU460893B2 (en) |
| BE (1) | BE808190A (en) |
| CA (1) | CA1016178A (en) |
| CH (1) | CH585749A5 (en) |
| DE (1) | DE2360355C3 (en) |
| ES (1) | ES421133A1 (en) |
| FR (1) | FR2208674B1 (en) |
| GB (1) | GB1457254A (en) |
| HU (1) | HU166457B (en) |
| IL (1) | IL43761A (en) |
| NL (1) | NL179056C (en) |
| NO (1) | NO138661C (en) |
| SE (3) | SE404605B (en) |
| ZA (1) | ZA739197B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5834235U (en) * | 1981-08-28 | 1983-03-05 | カシオ計算機株式会社 | Movable contact piece of push button switch |
| US5659051A (en) * | 1993-07-13 | 1997-08-19 | Sumitomo Chemical Company, Limited | Process of producing 2-cyano-4-oxo-4H-benzopyran compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3965122A (en) * | 1970-12-30 | 1976-06-22 | Fujisawa Pharmaceutical Co., Ltd. | Chromone compounds and preparation thereof |
-
1972
- 1972-12-05 GB GB5611772A patent/GB1457254A/en not_active Expired
-
1973
- 1973-11-28 CA CA186,922A patent/CA1016178A/en not_active Expired
- 1973-12-03 AU AU63133/73A patent/AU460893B2/en not_active Expired
- 1973-12-04 NL NLAANVRAGE7316575,A patent/NL179056C/en not_active IP Right Cessation
- 1973-12-04 HU HUMI549A patent/HU166457B/hu unknown
- 1973-12-04 AR AR251355A patent/AR199426A1/en active
- 1973-12-04 DE DE2360355A patent/DE2360355C3/en not_active Expired
- 1973-12-04 NO NO4621/73A patent/NO138661C/en unknown
- 1973-12-04 SE SE7316374A patent/SE404605B/en unknown
- 1973-12-04 JP JP13645773A patent/JPS533392B2/ja not_active Expired
- 1973-12-04 BE BE138487A patent/BE808190A/en not_active IP Right Cessation
- 1973-12-04 ZA ZA739197A patent/ZA739197B/en unknown
- 1973-12-04 ES ES421133A patent/ES421133A1/en not_active Expired
- 1973-12-04 FR FR7343175A patent/FR2208674B1/fr not_active Expired
- 1973-12-04 CH CH1697673A patent/CH585749A5/xx not_active IP Right Cessation
- 1973-12-05 IL IL43761A patent/IL43761A/en unknown
-
1974
- 1974-04-01 JP JP3572274A patent/JPS5336016B2/ja not_active Expired
-
1977
- 1977-01-21 SE SE7700663A patent/SE408420B/en unknown
- 1977-01-21 SE SE7700664A patent/SE408421B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE2360355A1 (en) | 1974-06-20 |
| SE408421B (en) | 1979-06-11 |
| JPS5336016B2 (en) | 1978-09-30 |
| NO138661C (en) | 1978-10-18 |
| NL7316575A (en) | 1974-06-07 |
| SE7700663L (en) | 1977-01-21 |
| SE404605B (en) | 1978-10-16 |
| ZA739197B (en) | 1974-10-30 |
| SE408420B (en) | 1979-06-11 |
| FR2208674A1 (en) | 1974-06-28 |
| BE808190A (en) | 1974-03-29 |
| JPS533392B2 (en) | 1978-02-06 |
| IL43761A0 (en) | 1974-03-14 |
| SE7700664L (en) | 1977-01-21 |
| AU6313373A (en) | 1975-05-08 |
| NL179056B (en) | 1986-02-03 |
| DE2360355C3 (en) | 1979-06-07 |
| CH585749A5 (en) | 1977-03-15 |
| DE2360355B2 (en) | 1978-10-12 |
| AR199426A1 (en) | 1974-08-30 |
| FR2208674B1 (en) | 1977-01-28 |
| JPS50111219A (en) | 1975-09-01 |
| NO138661B (en) | 1978-07-10 |
| CA1016178A (en) | 1977-08-23 |
| HU166457B (en) | 1975-03-28 |
| GB1457254A (en) | 1976-12-01 |
| ES421133A1 (en) | 1976-04-16 |
| JPS4993367A (en) | 1974-09-05 |
| AU460893B2 (en) | 1975-05-08 |
| NL179056C (en) | 1986-07-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4093734A (en) | Amino-benzoic acid amides | |
| JPH05155858A (en) | Novel benzimidazole and azabenzimidazole derivatives that are thromboxane acceptor antagonists, preparation thereof, and synthetic intermediate and medicinal composition containing same | |
| JPS5820954B2 (en) | Phenylsulfinyl composition | |
| JPH02117664A (en) | 4-pyridone-3-carboxylic acid and its derivative | |
| JPS5919090B2 (en) | Process for producing alkanolamine derivatives and acid addition salts thereof | |
| DE3419009A1 (en) | NEW SUBSTITUTED TO (4-AMINOPHENYL) SULPHONES, THEIR PRODUCTION AND THEIR USE AS MEDICINAL PRODUCTS | |
| PT87578B (en) | METHOD FOR PREPARING NEW ALKANO-SULFONANILIDA DERIVATIVES AND A PHARMACEUTICAL COMPOSITION THAT CONTAINS THEM | |
| GB2206347A (en) | Thiourea derivatives | |
| JPS62181246A (en) | Novel oxidated alkyl derivatives of glutamic acids and aspartic acids having antagonistic activity against bioactive polypeptides and manufacture | |
| US4238495A (en) | 1-(4-Cyano-phenoxy)-2-hydroxy-3-[2-(5-1H-tetrazolyl)-chromon-5-yloxy]-propane and salts thereof | |
| US3531493A (en) | Diphenylamine derivatives | |
| JPH0153266B2 (en) | ||
| JPS5846089A (en) | Heterocyclic compound | |
| IL43761A (en) | 1-(4-cyano-phenoxy)-2-hydroxy-3-(2-(5-1h-tetrazolyl)-chromon-5-yloxy)-propane and salts thereof their preparation and pharmaceutical compositions containing them | |
| GB1561731A (en) | Process for the preparation of benzopyrane derivatives | |
| US4350685A (en) | Antiallergic imidodisulfamides | |
| US4220645A (en) | Chromone derivatives | |
| EP0105131A1 (en) | 2-(Omega-alkylaminoalkyl)- and 2-(omega-dialkylaminoalkyl)-3-(4-X-benzylidene)-phthalimidines | |
| PL97347B1 (en) | METHOD OF MAKING NEW 2-PHENYLHYDRAZINE-THIAZOLINE OR-THIAZINE | |
| US3903159A (en) | Methanesulfonamidophenyl guanidine compounds | |
| US4313956A (en) | Novel sypathomimetic amine prodrugs | |
| US3697505A (en) | Aromatic substituted amidines | |
| US3875176A (en) | 2-benzoyl -3-amino-pyridines | |
| US5021429A (en) | Pharmacologically active aminoalkylphenyl compounds and their use | |
| JPS6056130B2 (en) | Novel salicylic acid derivatives |