FI80707B - Foerfarande foer framstaellning av terapeutiskt anvaendbara homonojirimycinglykosider. - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara homonojirimycinglykosider. Download PDFInfo
- Publication number
- FI80707B FI80707B FI854944A FI854944A FI80707B FI 80707 B FI80707 B FI 80707B FI 854944 A FI854944 A FI 854944A FI 854944 A FI854944 A FI 854944A FI 80707 B FI80707 B FI 80707B
- Authority
- FI
- Finland
- Prior art keywords
- dideoxy
- imino
- glycero
- guloheptitol
- benzyl
- Prior art date
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- -1 Homonojirimycin glycosides Chemical class 0.000 claims abstract description 48
- 150000001875 compounds Chemical class 0.000 claims abstract description 39
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 13
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 125000003147 glycosyl group Chemical group 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 5
- 238000007127 saponification reaction Methods 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 claims description 2
- 125000000089 arabinosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O)CO1)* 0.000 claims description 2
- 125000002446 fucosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O)[C@@H](O1)C)* 0.000 claims description 2
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 claims description 2
- 150000002402 hexoses Chemical class 0.000 claims description 2
- 125000001805 pentosyl group Chemical group 0.000 claims description 2
- 125000000969 xylosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 claims description 2
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims 1
- 150000001720 carbohydrates Chemical class 0.000 abstract description 6
- 238000006243 chemical reaction Methods 0.000 abstract description 3
- 229930182470 glycoside Natural products 0.000 abstract description 3
- 125000006239 protecting group Chemical group 0.000 abstract description 3
- CLVUFWXGNIFGNC-QTSLKERKSA-N (2r,3s,5r,6r)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol Chemical compound OC[C@H]1N[C@H](CO)[C@H](O)C(O)[C@@H]1O CLVUFWXGNIFGNC-QTSLKERKSA-N 0.000 abstract description 2
- 239000003112 inhibitor Substances 0.000 abstract description 2
- 102000038379 digestive enzymes Human genes 0.000 abstract 1
- 108091007734 digestive enzymes Proteins 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 37
- 239000000203 mixture Substances 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 14
- 239000008103 glucose Substances 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000006188 syrup Substances 0.000 description 10
- 235000020357 syrup Nutrition 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
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- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
- 235000000346 sugar Nutrition 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 5
- 235000014633 carbohydrates Nutrition 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- NSNHWTBQMQIDCF-UHFFFAOYSA-N dihydrate;hydrochloride Chemical compound O.O.Cl NSNHWTBQMQIDCF-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 150000002923 oximes Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
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- 238000003818 flash chromatography Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 150000002730 mercury Chemical class 0.000 description 3
- 239000001103 potassium chloride Substances 0.000 description 3
- 235000011164 potassium chloride Nutrition 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- OGOMAWHSXRDAKZ-BKJHVTENSA-N (3r,4s,5r,6r)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-ol Chemical compound C([C@H]1OC([C@@H]([C@@H](OCC=2C=CC=CC=2)[C@@H]1OCC=1C=CC=CC=1)OCC=1C=CC=CC=1)O)OCC1=CC=CC=C1 OGOMAWHSXRDAKZ-BKJHVTENSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- WRYNUJYAXVDTCB-UHFFFAOYSA-M acetyloxymercury Chemical compound CC(=O)O[Hg] WRYNUJYAXVDTCB-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
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- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- XYDYWTJEGDZLTH-UHFFFAOYSA-N methylenetriphenylphosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=C)C1=CC=CC=C1 XYDYWTJEGDZLTH-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
- Luminescent Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (11)
1. Förfarande för framställning av en terapeutiskt användbar förening med formeln (a)
5 HO-il M- NH H v X HO 4-1 CH2-OR
10 OH väri R är en glykosyl- eller en acylerad glykosylradikal, vilken innehäller 1-3 hexos- eller pentosenheter och bindningen tili glykosylradikalen sker i 1-ställningen, och av dess farmaceutiskt godtagbara syraadditionssalter, 15 kännetecknat därav, att en förening med formeln (b) CBZ BnO —η | )-N H f& BnO ^ CH20H OBn väri Bn är bensyl och DBZ är bensyloxikarbonyl, bringas 25 att reagera med en glykosylbromid eller -klorid, vars hydroxigrupp skyddats med bensylgrupp eller alkanoylgrupp som innehäller upp till 6 kolatomer, varefter man vid behov hydrerar katalytiskt eller förtvälar för att avlägs-na bensyl- eller esterskyddsgrupperna. 30 2. Förfarande enligt patentkravet 1 för framställ ning av en förening med formeln (a) HO-il H / \/ (a) 35 A/H s/\ 7 HO 4-T CH2-OR OH 24 8 0 7 0 7 väri R är glukosyl, galaktosyl, fukosyl, ribosyl, cello-biosyl, maltotriosyl, cellotriosyl, arabinosyl eller xy-losyl, kännetecknat därav, att en förening med formeIn (b)
5 CBZ BnO-1 | )-N H /λΧ BnO -f CH20H
10 OBn väri Bn är bensyl och CBZ är bensyloxikarbonyl, bringas att reagera med en glykosylbromid eller -klorid, väri glykosylen är den samma som den ovan definierade gruppen 15 R, vilkens hydroxigrupper skyddats med bensylgrupper eller alkanoylgrupper som innehäller upp tili 6 kolatomer, var-efter man vid behov hydrerar katalytiskt eller förtvälar för att avlägsna bensyl- eller esterskyddsgrupperna.
3. Förfarande enligt patentkravet 1 för framställ-20 ning av en förening med formeln (a) H0—iL —NH H , x 25 3/vX HO 4-f CH2-OR OH väri R är glukosyl, L-fukosyl eller cellobiosyl, kännetecknat därav, att en förening med form-30 eln (b) CBZ BnO-1 | )-N H (b) L OBn Y
35 NZA BnO \ CH20H OBn 25 80707 väri Bn är bensyl och CBZ är bensyloxikarbonyl, bringas att reagera med en glykosylbromid eller -klorid, vari glykosylen är den sanuna som ovan definierade gruppen R, vilkens hydroxigrupper skyddats med bensylgrupper eller 5 alkanoylgrupper som innehäller upp till 6 kolatomer, var-efter man vid behov hydrerar katalytiskt eller förtvälar för att avlägsna bensyl- eller esterskyddsgrupperna.
4. Förfarande enligt patentkravet 1 för framställ-ning av 2,6-imino-2,6-dideoxi-7-0-(β-D-glukopyranosyl)-D-10 glycero-L-guloheptitol, kännetecknat därav, att 2,6-dideoxi-2,6-{[(fenylmetoxi)karbonyl]imino}- 1,3,4,5-tetrakis-0-( fenylmetyl )-D-glycero-L-guloheptitol bringas att reagera med 2,3,4,6-tetra-0-(fenylmetyl)a-D-glukopyranosylbromid och sedan hydreras katalytiskt. 15 5. Förfarande enligt patentkravet 1 för framställ- ning av 2,6-imino-2,6-dideoxi-7-0-(β-D-glukopyranosyl)-D-glycero-L-guloheptitol, kännetec knat därav, att 2,6-dideoxi-2,6 — {[(fenylmetoxi)karbonyl]imino}- 1,3,4, 5-tetrakis-O- ( fenylmetyl)-D-glycero-L-guloheptitol 20 bringas att reagera med 2,3,4,6-tetraacetyl-a-D-glukopyra- nosylbromid och sedan med natriummetoxid i metanol och sedan hydreras katalytiskt.
6. Förfarande enligt patentkravet 1 för framställ-ning av 2,6-imino-2,6-dideoxi-7-0-(6-deoxi-3~D-gaalktopy- 25 ranosyl)-D-glycero-L-guloheptitol, känneteck nat därav, att 2,6-dideoxi-2,6-{[(fenylmetoxi)karbo-nyl]imino}-l,3,4,5-tetrakis-0-(fenylmetyl)-D-glycero-L-guloheptitol bringas att reagera med 2,3,4-triacetyl-6-deoxi-a-D-galaktopyranosylklorid och sedan med natrium-30 metoxid i metanol och sedan hydreras katalytiskt.
7. Förfarande enligt patentkravet 1 för framställ-ning av 2,6-imino-2,6-dideoxi-7-0-(6-deoxi-p-L-galaktopy-ranosyl)-D-glycero-L-guloheptitol, kännetecknat därav, att 2,6-dideoxi-2,6-{[(fenylmetoxi)karbo- 35 nyl]irnino}-!,3,4,5-tetrakis-0-(fenylmetyl)-D-glycero-L- 26 80707 guloheptitol bringas att reagera med 2,3,4-triacetyl-6-deoxi-a-L-galaktopyranosylklorid och sedan med natrium-metoxid i metanol och sedan hydreras katalytiskt.
8. Förfarande enligt patentkravet 1 för framställ-5 ning av 0-p-D-glukopyranosyl-( 1 >4)-0-p-D-glukopyranosyl-(1 >7)-2,6-dideox±-2,6-imino-D-glycero-L-guloheptitol, kännetecknat därav, att 2,6-dideoxi-2,6-{[(fe-nylmetoxi) karbonyl ] imino} -1,3,4,5-tetrakis-O- (f enylmetyl) -D-glycero-L-guloheptitol bringas att reagera med 4-0-10 (2,3,4,6-tetra-O-acetyl-p-D-glukopyranosyl-a-D-glukopyra- nosylbromidtriacetat och sedan med natriummetoxid i metanol och sedan hydreras katalytiskt.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US68312784 | 1984-12-18 | ||
| US06/683,127 US4634765A (en) | 1984-12-18 | 1984-12-18 | Homodisaccharide hypoglycemic agents |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI854944A0 FI854944A0 (fi) | 1985-12-13 |
| FI854944L FI854944L (fi) | 1986-06-19 |
| FI80707B true FI80707B (fi) | 1990-03-30 |
| FI80707C FI80707C (sv) | 1990-07-10 |
Family
ID=24742682
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI854944A FI80707C (sv) | 1984-12-18 | 1985-12-13 | Förfarande för framställning av terapeutiskt användbara homonojirimyci nglykosider |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4634765A (sv) |
| EP (1) | EP0186103B1 (sv) |
| JP (1) | JPS61158994A (sv) |
| KR (1) | KR900005607B1 (sv) |
| CN (1) | CN1016784B (sv) |
| AT (1) | ATE62249T1 (sv) |
| AU (1) | AU574246B2 (sv) |
| CA (1) | CA1240989A (sv) |
| DE (1) | DE3582420D1 (sv) |
| DK (1) | DK587085A (sv) |
| ES (1) | ES8706164A1 (sv) |
| FI (1) | FI80707C (sv) |
| GR (1) | GR853032B (sv) |
| HU (1) | HU194263B (sv) |
| IE (1) | IE58186B1 (sv) |
| NO (1) | NO162387B (sv) |
| NZ (1) | NZ214570A (sv) |
| PH (1) | PH23660A (sv) |
| PT (1) | PT81689B (sv) |
| ZA (1) | ZA859573B (sv) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2181729B (en) * | 1985-10-12 | 1990-04-04 | Nippon Shinyaku Co Ltd | Glucosylmoranoline derivatives and production thereof |
| JPS62242692A (ja) * | 1986-04-15 | 1987-10-23 | Nippon Shinyaku Co Ltd | モラノリン誘導体の製造法 |
| EP0345104B1 (en) * | 1988-06-02 | 1995-11-02 | Merrell Dow Pharmaceuticals Inc. | Novel Alpha-glucosidase inhibitors |
| EP0344383A1 (en) * | 1988-06-02 | 1989-12-06 | Merrell Dow Pharmaceuticals Inc. | Novel alpha-Glucosidase inhibitors |
| US4880917A (en) * | 1988-07-01 | 1989-11-14 | Merrell Dow Pharmaceuticals Inc. | Process for hydrolyzing 2,6-dideoxy-2,6-iminoheptononitrile derivatives using trifluoroacetic acid and dinitrogen tetroxide |
| US4908439A (en) * | 1988-09-16 | 1990-03-13 | Merrell Dow Pharmaceuticals Inc. | Synthesis of intermediate useful in the preparation of nojirimycin and related compounds |
| US5227479A (en) * | 1989-12-20 | 1993-07-13 | Merrell Dow Pharmaceuticals Inc. | Process for the preparation of nojirimycin and related compounds |
| US5504078A (en) * | 1990-06-08 | 1996-04-02 | Merrell Dow Pharmaceuticals Inc. | α-glucosidase inhibitors |
| CN101239089A (zh) * | 1997-04-15 | 2008-08-13 | Csir公司 | 具有食欲抑制剂活性的药物组合物 |
| GB2396815B (en) * | 1999-10-27 | 2004-09-08 | Phytopharm Plc | A composition comprising a pregnenone derivative and an NSAID |
| US6462197B2 (en) | 2000-03-31 | 2002-10-08 | Board Of Trustees Of Michigan State University | Process for the preparation of 1,5-dideoxy-1,5-imino hexitols from oximes or imines |
| GB2363985B (en) | 2000-06-30 | 2004-09-29 | Phytopharm Plc | Extracts,compounds & pharmaceutical compositions having anti-diabetic activity and their use |
| US7262318B2 (en) * | 2004-03-10 | 2007-08-28 | Pfizer, Inc. | Substituted heteroaryl- and phenylsulfamoyl compounds |
| US20050288340A1 (en) * | 2004-06-29 | 2005-12-29 | Pfizer Inc | Substituted heteroaryl- and phenylsulfamoyl compounds |
| MX2007005137A (es) * | 2004-11-23 | 2007-06-22 | Warner Lambert Co | Derivados del acido 7-(2h-pyrazol-3-il)-3, 5-dihidroxi-heptanoico como inhibidores de hmg co-a reductasa para el tratamiento de lipidemia. |
| US20060293250A1 (en) * | 2005-06-08 | 2006-12-28 | Michael Major | Crystalline sugar compositions and method of making |
| JP2008545800A (ja) * | 2005-06-08 | 2008-12-18 | アミカス セラピューティックス インコーポレイテッド | トリフラート化化合物の安定化 |
| PT2027137E (pt) * | 2005-06-08 | 2015-06-09 | Amicus Therapeutics Inc | Purificação de imino e amino-açúcares |
| US7741317B2 (en) | 2005-10-21 | 2010-06-22 | Bristol-Myers Squibb Company | LXR modulators |
| US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
| WO2008070496A2 (en) | 2006-12-01 | 2008-06-12 | Bristol-Myers Squibb Company | N- ( (3-benzyl) -2, 2- (bis-phenyl) -propan-1-amine derivatives as cetp inhibitors for the treatment of atherosclerosis and cardiovascular diseases |
| ATE518544T1 (de) | 2007-03-12 | 2011-08-15 | Zadec Aps | Rotbusch-extrakt gegen diabetes |
| EP2170930B3 (en) | 2007-06-04 | 2013-10-02 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| JP2011522828A (ja) | 2008-06-04 | 2011-08-04 | シナジー ファーマシューティカルズ インコーポレイテッド | 胃腸障害、炎症、癌、およびその他の障害の治療のために有用なグアニル酸シクラーゼのアゴニスト |
| EP2321341B1 (en) | 2008-07-16 | 2017-02-22 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| JP2013528172A (ja) | 2010-05-21 | 2013-07-08 | ファイザー・インク | ２−フェニルベンゾイルアミド |
| US20130156720A1 (en) | 2010-08-27 | 2013-06-20 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| CN102462726B (zh) * | 2010-11-04 | 2016-03-09 | 中国医学科学院药物研究所 | 白树总生物碱及多羟基生物碱化合物的提取、分离及用途 |
| US20130345392A1 (en) | 2011-03-04 | 2013-12-26 | Pfizer Inc | Edn3-like peptides and uses thereof |
| CN103703012A (zh) * | 2011-05-13 | 2014-04-02 | 格礼卡姆股份公司 | 乳糖-n-四糖的制造 |
| WO2013133685A1 (en) | 2012-03-09 | 2013-09-12 | Biotropics Malaysia Berhad | Extract formulations of rhodamnia cinerea and uses thereof |
| US9708367B2 (en) | 2013-03-15 | 2017-07-18 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase and their uses |
| CA2905435A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| BR112015026513A2 (pt) | 2013-04-17 | 2017-07-25 | Pfizer | derivados de n-piperidin-3-ilbenzamida para tratar as doenças cardiovasculares |
| RS65632B1 (sr) | 2013-06-05 | 2024-07-31 | Bausch Health Ireland Ltd | Ultra-prečišćeni agonisti guanilat-ciklaze c, postupak njihove pripreme i upotrebe |
| CN113121450A (zh) | 2014-08-29 | 2021-07-16 | Tes制药有限责任公司 | α-氨基-β-羧基粘康酸半醛脱羧酶抑制剂 |
| WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
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| IT201700078102A1 (it) | 2017-07-11 | 2019-01-11 | Dipharma Francis Srl | Sintesi di un azazucchero e suoi intermedi |
| CN108828121B (zh) * | 2018-06-14 | 2020-06-05 | 华润三九医药股份有限公司 | 一种白树药材中α-高野尻霉素的含量检测方法 |
| IL283182B2 (en) | 2018-11-20 | 2025-10-01 | Tes Pharma S R L | Alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase inhibitors |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4065562A (en) * | 1975-12-29 | 1977-12-27 | Nippon Shinyaku Co., Ltd. | Method and composition for reducing blood glucose levels |
| NO154918C (no) * | 1977-08-27 | 1987-01-14 | Bayer Ag | Analogifremgangsmaate til fremstilling av terapeutisk aktive derivater av 3,4,5-trihydroksypiperidin. |
| DE2848117A1 (de) * | 1978-11-06 | 1980-05-14 | Bayer Ag | Derivate des 2-hydroxymethyl-3,4,5- trihydroxy-piperidins, ihre herstellung und verwendung zur beeinflussung des kohlenhydrat- und fettstoffwechsels |
| DE2942365A1 (de) * | 1979-10-19 | 1981-05-14 | Bayer Ag, 5090 Leverkusen | 2-hydroxyalkyl-3,4,5-trihydroxy-(pi)-peridine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| GB2064527B (en) * | 1979-12-08 | 1984-05-02 | Nippon Shinyaku Co Ltd | Moranoline derivatives and process for preparation thereof |
| IT1210476B (it) * | 1981-05-28 | 1989-09-14 | Erba Farmitalia | Antracicline. |
-
1984
- 1984-12-18 US US06/683,127 patent/US4634765A/en not_active Expired - Lifetime
-
1985
- 1985-12-05 AU AU50810/85A patent/AU574246B2/en not_active Ceased
- 1985-12-13 FI FI854944A patent/FI80707C/sv not_active IP Right Cessation
- 1985-12-13 CA CA000497607A patent/CA1240989A/en not_active Expired
- 1985-12-13 ZA ZA859573A patent/ZA859573B/xx unknown
- 1985-12-16 HU HU854804A patent/HU194263B/hu not_active IP Right Cessation
- 1985-12-16 IE IE317985A patent/IE58186B1/en not_active IP Right Cessation
- 1985-12-16 PT PT81689A patent/PT81689B/pt not_active IP Right Cessation
- 1985-12-16 NZ NZ214570A patent/NZ214570A/en unknown
- 1985-12-17 JP JP60282167A patent/JPS61158994A/ja active Granted
- 1985-12-17 EP EP85116117A patent/EP0186103B1/en not_active Expired - Lifetime
- 1985-12-17 CN CN85109548A patent/CN1016784B/zh not_active Expired
- 1985-12-17 GR GR853032A patent/GR853032B/el unknown
- 1985-12-17 DE DE8585116117T patent/DE3582420D1/de not_active Expired - Fee Related
- 1985-12-17 NO NO855087A patent/NO162387B/no unknown
- 1985-12-17 DK DK587085A patent/DK587085A/da not_active Application Discontinuation
- 1985-12-17 AT AT85116117T patent/ATE62249T1/de not_active IP Right Cessation
- 1985-12-17 ES ES550060A patent/ES8706164A1/es not_active Expired
- 1985-12-18 KR KR1019850009529A patent/KR900005607B1/ko not_active Expired
- 1985-12-18 PH PH33204A patent/PH23660A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT81689A (en) | 1986-01-01 |
| IE58186B1 (en) | 1993-07-28 |
| NO162387B (no) | 1989-09-11 |
| AU5081085A (en) | 1986-06-26 |
| CN1016784B (zh) | 1992-05-27 |
| FI854944A0 (fi) | 1985-12-13 |
| EP0186103B1 (en) | 1991-04-03 |
| JPS61158994A (ja) | 1986-07-18 |
| ES8706164A1 (es) | 1987-06-01 |
| IE853179L (en) | 1986-06-18 |
| KR900005607B1 (ko) | 1990-07-31 |
| US4634765A (en) | 1987-01-06 |
| ES550060A0 (es) | 1987-06-01 |
| HU194263B (en) | 1988-01-28 |
| FI854944L (fi) | 1986-06-19 |
| CN85109548A (zh) | 1986-07-09 |
| EP0186103A3 (en) | 1988-02-03 |
| DK587085A (da) | 1986-06-19 |
| KR860004921A (ko) | 1986-07-16 |
| FI80707C (sv) | 1990-07-10 |
| ZA859573B (en) | 1986-08-27 |
| CA1240989A (en) | 1988-08-23 |
| HUT40137A (en) | 1986-11-28 |
| PT81689B (pt) | 1987-11-30 |
| JPH0565519B2 (sv) | 1993-09-17 |
| PH23660A (en) | 1989-09-27 |
| GR853032B (sv) | 1986-04-18 |
| NO855087L (no) | 1986-06-19 |
| NZ214570A (en) | 1988-03-30 |
| DE3582420D1 (de) | 1991-05-08 |
| AU574246B2 (en) | 1988-06-30 |
| EP0186103A2 (en) | 1986-07-02 |
| ATE62249T1 (de) | 1991-04-15 |
| DK587085D0 (da) | 1985-12-17 |
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