IL32814A - Water soluble 16alpha-methyl-11beta,21-dihydroxy-pregna-1,4-diene-3,20-dione 21-esters - Google Patents
Water soluble 16alpha-methyl-11beta,21-dihydroxy-pregna-1,4-diene-3,20-dione 21-estersInfo
- Publication number
- IL32814A IL32814A IL32814A IL3281469A IL32814A IL 32814 A IL32814 A IL 32814A IL 32814 A IL32814 A IL 32814A IL 3281469 A IL3281469 A IL 3281469A IL 32814 A IL32814 A IL 32814A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- acid
- converted
- manufacture
- resulting
- Prior art date
Links
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 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 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 229910052708 sodium Inorganic materials 0.000 claims description 10
- 239000011734 sodium Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- -1 sulphuric acid ester Chemical class 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000001117 sulphuric acid Substances 0.000 claims 3
- 235000011149 sulphuric acid Nutrition 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 229910001511 metal iodide Inorganic materials 0.000 claims 1
- 239000000243 solution Substances 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 239000005662 Paraffin oil Substances 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000002304 perfume Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 206010040070 Septic Shock Diseases 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 150000002440 hydroxy compounds Chemical class 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- 229910021653 sulphate ion Inorganic materials 0.000 description 2
- 239000003871 white petrolatum Substances 0.000 description 2
- DRTQHJPVMGBUCF-UCVXFZOQSA-N 1-[(2s,3s,4s,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@H]1[C@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UCVXFZOQSA-N 0.000 description 1
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 1
- DFGKGUXTPFWHIX-UHFFFAOYSA-N 6-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]acetyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)C1=CC2=C(NC(O2)=O)C=C1 DFGKGUXTPFWHIX-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910001516 alkali metal iodide Inorganic materials 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/046—Aerosols; Foams
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0066—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by a carbon atom forming part of an amide group
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Dispersion Chemistry (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Water soluable The present 1s concerned with new and with their manufacture and The present Invention provides compounds of the general formula CH20Y or Inorganic represents 2 or and and each representing a lower alkyl group or and together the N to which they are attached representing a or a In Israeli patents 12 12 11 249 and 1n German Patent the preparation of salts of esters of cortlcold steroids which dissolve water are described however said patents do not teach or suggest the subject matter of the present In the endotoxin shock test the new compounds are superior to the known used as standard as as in the eosinophHene as 1B shown 1n the following a En t a n c e I Sodium meth 1000 2400 6ooo sulphate hemisulphate II 200 14o III 20 40 IV 14 25 chloride The activity on the endotoxin shock was determined by a modification of the experiment described by Brooke y page in the following each weighin 100 to 120 were adrenalectomized and on the following day given g of bodywelght of endotoxin intravenously under a light ether Immediately after the injection the cortlcoid was administered through the same and the dose was established after the administration of which the rats survived for 24 The eoslnophllene test according to Speirs and Meyer the modified was also carried out on adrenalectomized having determined the number for each it was given subcutaneously g of bodywelght of the solution under after the injection blood was taken from the tall vein and the eosinophilene number was and compared with the previously found starting The dos which lowered the eosinophilene numbe by results summarized the Table clearly shown that the activity on the endotoxin shock and the lowering effect upon eosinophilene very much more distinct with the oompounds II to IV of the present Invention than with the control substance A from 14 to of the new compounds achieved the same effect as 1000 to of the control The new active compounds can be administered in an aqueous solution parenterally or Aqueous solutions of the preparations are always preferred when is necessary for the administered substance to as quickly and intensively as By virtue of their excellent pharmacological properties the followin Indications are suitable for parenteral Shock after an failure of blood circulation afte heart infarct lung for the treatment of serious and allergic Status trouble caused by contrast agents and the The active compounds can also be used with advantage Inflammation inhibitors aqueous nose and ear where the otherwise indispensable oily solution promoters often produce undesirable side the present Invention also provides pharmaceutica preparations comprise compounds of the general formula admixture conjunction with a pharmaceutically suitable The present invention provides also a process for the manufacture of the oompounds of the general formula wherein the corresponding compounds are a known maimer likewise a known the resulting esters are then converted into salts tolerable bases or To manufacture the metal salts compounds of the general formula in which represents an the corresponding compounds are converted in a known especially by reaction with a trloxide the acid sulphuric acid esters and the latter are the likewise in a known salts thereof with physiologically tolerable alkali As such physiologically tolerable there may mentioned the hydroxide butylate like of an alkali especially of The acid metal salts of the present Invention compounds of the general formula which Y represents a are likewise manufactured a known for the corresponding hydroxy compounds may be first converted with a preferably in pyridine into the heating the 21isulphonates with an alkali metal Iodide in acetone the compounds are obtained whic are then heated wit phosphoric acid in the of an organic base in an whereby the are The organic base used for the reaction with phosphoric acid may be an alkylated for example Suitable inert solvents a for example dimethyl sulphoxlde or For manufacture of the alkali metal salts the phosphoric acid monoesters are mixed with an alkali an alcoholic solutio until a of 11 been The ealt precipitated from the solution ether and isolated h be manufactured by known methods from the corresponding 2 hydroxy compounds for the corresponding compounds concerted with a derivative of a for example chloroacetic bromoacetyl bromide or in the presence of an organic for example into the It is advantageous to carry out the reaction in the presenoe of an inert for in at first while cooling and then it is completed at room The halogenoacylate then cted with an amine of the general formula to form the amine there is preferably for a secondary aliphatic o for example pipera or an or The reaction of with the amine carried out b simply mixing and heating the two excess amine serves as solvent during the In the reaction can also be performed in a dilute The thus obtained can be converted by known methods acids the corresponding acid addition salts The addition salts may be formed with those ally tolerables acids normally with organic nitrogen o acids for nicotinic acid The following Examples the 1 40 ml yridine were cooled to and 59 ml of freshly distilled sulphur trioxide were stirred in dropwlse at such a rate that the internal temperature did not rise above Then 20 g of were added to this solution while flushing ml of The reaction mixture was stirred for minutes at room diluted 400 ml f stirred for a further 30 minutes and adjusted to a of with ml of hydroxide The pyridine was removed by extraction with methylene The e of the aqueous solution was readjusted to 8 with sodium hydroxide and the solution was under vacuum at a bath residue was dissolved ml of the sodium dulphate was filtered off and the filtrate was evaporated under vacuum and to yield sodium melting at with Ultraviolet of the Example 2 A solution of g of 10 ml of pyridine was stirred with 0 g of adduot 12 hours at room The reaction solution was then mixed with ml of stirred for 2 hours and added dropwlse to 100 ml of The precipitate formed was filtered off washed with ether dissolved in 15 ml of absolute The solution was adjusted to with was filtered off The filtrate was concentrated with the precipitate formed was filtered off with suction and dried under vaccum at to yield pregnadl sulphate melting at with Example 3 A solution of 8 m in 10 ml of pyridine with g of adduct was stirred for 12 hours at room temperature under The reaction solution was then mixed ml of stirred for 2 hours and added dropwise to 100 ml of dry The precipitate formed was filtered off washed ether and dissolved in 15 ml of absolute The solution adjusted to a alue of with left to stand for 16 adjusted to a pH value of and the precipitated sodium sulphate was filtered off with The filtrate was concentrated and mixed precipitate formed was filtered off with suction and The resulting sodium melted at with of the theoretical Example 4 20 ml of thane sulphonyl chloride was stirred dropwise into a cooled solution 20 g of 200 ml of After a reaction time of 30 minutes the reaction solution was poured into and the precipitated was filtered Grams of the resulting were dissolved in 500 ml of g of sodium iodide in 400 ml of acetone were added and the whole was heated for 15 minutes at the The filtered reaction solution was evaporated under residue was stirred with diluted sodium thiosulphate filtered with washed with dissolved 300 ml of acetone and while being heated precipitated wi th 120 of After g of thy decomposed at 157 160 were Grams of the compound were dissolved in ml of acetonltrlle and refluxed for 3 hours with 1 ml of orthophosphorlc acid and 42 ml of trie thy The reaction solution then concentrated under the residue taken up i methanol and the solution was adjusted to alue of 11 with sodium hydroxide The was filtered the filtrate evaporated under vacGum the residue was taken up in 70 ml of and the salt was precipitated by adding The dlsodium jsalt can be purified by repreclpitation from methanol with g of dlsodium Ultraviolet χ Example 5 3 Grams of f were reacted and worked up as described Example to g of dlsodium c 1 in Example 6 then coo ed to room diluted with ch oroform evaporated under The residue was taken up chloroform and washed with dilute bicarbonate solution and The solution was dried over sodium sulphate and evaporated under to yield g of as a viscid oil was taken up in 300 ml of clarified by through and ethereal hydrochloric acid was added until an acid reaction to Congo red had been of After purification b reprecipitation from a methanolic solution with ether the pure hydrochloride melted at 227 Example A 1 of as described in Example in 20 ml of dioxan was mixed with a solution of ml of plperldlne in 2 of dioxan and the whole was stirred for 24 hours at The residue was filtered off with suction he filtrate was evaporated under The residue was stirred for about 15 minutes with 50 ml of the filtered off suction and washed with to yield g of after from melted at 232 with Gram of the above compound w suspended in ml of methanol ethereal hydrochloric acid was to yield g of hydrochloride melting at 242 with Example 9 Gram of Exampli was reacted with ml of morphollne and worked up as described in Example to yield g of converted into the as described in Example Melting point 211 c with E of at 132 When 4 g of the above compound were treated with ethereal acid as described Example there w re obtained g of hydrochloride melting at 221 Example 12 A solution of g of in 50 ml of absolute dloxan was mixed with ml of pyridine then a solution Of g of in 25 ml fo abso lute ether was added dropwise the whole was stirred for 24 hours room then diluted with and the organic phase was repeatedly Washed with water dried over sodium sulphate and After recrystallizatlon from ethyl acetate hexane there Composition of eyedrops g of sodium f of sodium mercurlthloaalicylate g of g of sodium hydroxide and of sodium chloride were dissolved in of distilled water filtered und er sterile and bottled under aseptiiS conditions 14 Composition of eyedrop of sodium f 3 benzoic methyl g of propyl ester g of citric g of sodium hydroxide and g of sodium chloride were dissolved in g of disti lled water fi ltered under sterile conditions and bottled under conditions Example 15 Composition of a sprayj g of sodium 6 16 of an aliphatic polyglycol g of paraffin oil of g of stearyl alcohol g of c acid methyl of acid propyl g of perfume oil g of water grama The spray was manufactured in the usual Example 16 Composition of an i g of sodium meth g of white petroleum jelly g of paraffin oil g of white of a mixed ester of high molecular from ra materials close to natual products g of perfume oil g of paraffin oil white petroleum g of glycerin and g of stea l g of hydro acid methyl g of acid propyl g of perfume g of of paraffin oil g of white petroleum Jelly g of glycerin and g of a old methyl of b acid propyl of perfume g of water grams insufficientOCRQuality
Claims (1)
1. What we claim A compound of the general formula representing a physiologically tolerable organic or rerpesenting 2 or and and each representing a lower alkyl group or and together with the N to which they are attached representing a or a A compound as claimed in claim wherein represents Sodium phate 1 thy pharmaceu ical y su tab e A pharmaceutical preparation which comprises the compound claimed any of claims 3 to admixture or conjunction with a pharmaceutically suitable A pharmaceutical preparation a Bubstantially as described in any of Examples 13 to A process for the manufacture a as claimed in tolerable process for the of a compound as claimed in claim 1 in which Y represents an wherein the corresponding converted into an acid sulphuric acid and the acid sulphuric acid ester is then converted into a thereof a physiologically alkali A process as claimed in claim wherein the conversion of th into the acid sulphuric acid ester is carried out by treatmen ith a A process for the manufacture of a compound as claimed claim 1 in which Y represents a wherein correspondlns compound is in the with the resulting converted the corresponding compound with an metal iodide in the resulting iodo compound is reacted with phosphoric acid the presence of an organic base and the resulting phosphoric acid monoester converted into a alkall metal salt thereof by means of A process for the manufacture of a compound as claimed represents a or wherein the correspondi g compound a derivative of a acid presence of an organic the resulting a addition salt thereof a physiologically tolerable A process claimed wherei the organic base is process for the manufacture of a compound as claimed conducted substantially as described i any one of Examples 1 to 12 Bregman and insufficientOCRQuality
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19681793218 DE1793218C3 (en) | 1968-08-17 | 1968-08-17 | Water-soluble 21-hemisulfate alkali metal compounds of 6 a-fluoro-11 ß, 21-dihydroxy-16 a-methyl-3,20-dioxo-1,4-pregnadienes, processes for their preparation and pharmaceuticals containing them |
DE1902651A DE1902651C3 (en) | 1969-01-15 | 1969-01-15 | New corticosteroid-21-monophosphates, processes for their preparation and medicinal products containing them |
DE19691920634 DE1920634C3 (en) | 1969-04-19 | 1969-04-19 | Water-soluble corticosteroid-21-aminoacylates, processes for their preparation and pharmaceuticals containing them |
Publications (2)
Publication Number | Publication Date |
---|---|
IL32814A0 IL32814A0 (en) | 1969-11-12 |
IL32814A true IL32814A (en) | 1973-06-29 |
Family
ID=27181456
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL32814A IL32814A (en) | 1968-08-17 | 1969-08-11 | Water soluble 16alpha-methyl-11beta,21-dihydroxy-pregna-1,4-diene-3,20-dione 21-esters |
Country Status (11)
Country | Link |
---|---|
BE (1) | BE737501A (en) |
BR (1) | BR6911575D0 (en) |
CH (1) | CH527177A (en) |
ES (1) | ES370164A1 (en) |
FR (1) | FR2015858A1 (en) |
GB (1) | GB1286093A (en) |
IL (1) | IL32814A (en) |
NL (1) | NL6912571A (en) |
NO (1) | NO131427C (en) |
SE (1) | SE352348B (en) |
YU (1) | YU34304B (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2715853A1 (en) * | 1977-04-06 | 1978-10-19 | Schering Ag | WATER-SOLUBLE CORTICOIDS |
DE2920726A1 (en) * | 1979-05-18 | 1980-11-27 | Schering Ag | NEW CORTICOIDS, THEIR PRODUCTION AND USE |
US4456602A (en) * | 1982-08-23 | 1984-06-26 | The Upjohn Company | Amine containing ester prodrugs of corticosteroids |
US4443440A (en) * | 1982-08-30 | 1984-04-17 | The Upjohn Company | Amine containing ester prodrugs of corticosteroids |
JP6090514B1 (en) * | 2016-05-18 | 2017-03-08 | 日本ゼオン株式会社 | Method for producing polymerizable compound |
CN110800738A (en) * | 2019-11-11 | 2020-02-18 | 福州科理技术开发有限公司 | Deodorizing and pest killing spray liquid for kitchen garbage and its prepn |
-
1969
- 1969-07-21 YU YU1889/69A patent/YU34304B/en unknown
- 1969-07-23 CH CH1128069A patent/CH527177A/en not_active IP Right Cessation
- 1969-08-01 ES ES370164A patent/ES370164A1/en not_active Expired
- 1969-08-11 IL IL32814A patent/IL32814A/en unknown
- 1969-08-14 BE BE737501D patent/BE737501A/xx unknown
- 1969-08-15 NO NO3303/69A patent/NO131427C/no unknown
- 1969-08-15 BR BR211575/69A patent/BR6911575D0/en unknown
- 1969-08-15 SE SE11408/69A patent/SE352348B/xx unknown
- 1969-08-18 GB GB41152/69A patent/GB1286093A/en not_active Expired
- 1969-08-18 FR FR6928228A patent/FR2015858A1/fr not_active Withdrawn
- 1969-08-18 NL NL6912571A patent/NL6912571A/xx not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
NO131427C (en) | 1975-05-28 |
NO131427B (en) | 1975-02-17 |
BE737501A (en) | 1970-02-16 |
SE352348B (en) | 1972-12-27 |
FR2015858A1 (en) | 1970-04-30 |
NL6912571A (en) | 1970-02-19 |
YU34304B (en) | 1979-04-30 |
CH527177A (en) | 1972-08-31 |
YU188969A (en) | 1978-10-31 |
ES370164A1 (en) | 1971-04-01 |
GB1286093A (en) | 1972-08-16 |
BR6911575D0 (en) | 1973-02-13 |
IL32814A0 (en) | 1969-11-12 |
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