NO317303B1 - Pyrazolo[1,5-a]pyrimidin-derivater - Google Patents
Pyrazolo[1,5-a]pyrimidin-derivater Download PDFInfo
- Publication number
- NO317303B1 NO317303B1 NO20005820A NO20005820A NO317303B1 NO 317303 B1 NO317303 B1 NO 317303B1 NO 20005820 A NO20005820 A NO 20005820A NO 20005820 A NO20005820 A NO 20005820A NO 317303 B1 NO317303 B1 NO 317303B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- hydrogen
- compound
- group
- halogen
- Prior art date
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- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 title claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 55
- 239000001257 hydrogen Substances 0.000 claims abstract description 45
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 19
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 230000000202 analgesic effect Effects 0.000 claims abstract description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
- -1 phenylethynyl Chemical group 0.000 claims description 255
- 150000001875 compounds Chemical class 0.000 claims description 195
- 125000001424 substituent group Chemical group 0.000 claims description 59
- 229910052736 halogen Inorganic materials 0.000 claims description 35
- 150000002367 halogens Chemical class 0.000 claims description 35
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 27
- 238000002360 preparation method Methods 0.000 claims description 24
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 10
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000005504 styryl group Chemical group 0.000 claims description 4
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 150000003230 pyrimidines Chemical class 0.000 claims description 3
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 206010040047 Sepsis Diseases 0.000 abstract description 2
- 206010040070 Septic Shock Diseases 0.000 abstract description 2
- 230000001684 chronic effect Effects 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 230000000069 prophylactic effect Effects 0.000 abstract description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 abstract description 2
- 208000013223 septicemia Diseases 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 102000003960 Ligases Human genes 0.000 abstract 1
- 108090000364 Ligases Proteins 0.000 abstract 1
- 229940035676 analgesics Drugs 0.000 abstract 1
- 239000000730 antalgic agent Substances 0.000 abstract 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 73
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000012442 inert solvent Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 239000013078 crystal Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 238000000034 method Methods 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 238000002844 melting Methods 0.000 description 14
- 230000008018 melting Effects 0.000 description 14
- 239000003826 tablet Substances 0.000 description 13
- 239000003513 alkali Substances 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 239000011630 iodine Substances 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- OPHQOIGEOHXOGX-UHFFFAOYSA-N 3,4,5-trimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1OC OPHQOIGEOHXOGX-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N DBU Substances C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 208000000114 Pain Threshold Diseases 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 239000012024 dehydrating agents Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- SIGOIUCRXKUEIG-UHFFFAOYSA-N methyl 2-dimethoxyphosphorylacetate Chemical compound COC(=O)CP(=O)(OC)OC SIGOIUCRXKUEIG-UHFFFAOYSA-N 0.000 description 4
- 230000037040 pain threshold Effects 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- PFCWPLNWVMUWHZ-UHFFFAOYSA-N 5-butyl-7-(diethoxyphosphorylmethyl)pyrazolo[1,5-a]pyrimidine Chemical compound N1=C(CCCC)C=C(CP(=O)(OCC)OCC)N2N=CC=C21 PFCWPLNWVMUWHZ-UHFFFAOYSA-N 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 239000005995 Aluminium silicate Substances 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 235000012211 aluminium silicate Nutrition 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 229940110456 cocoa butter Drugs 0.000 description 3
- 235000019868 cocoa butter Nutrition 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 210000000548 hind-foot Anatomy 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
- 229910000105 potassium hydride Inorganic materials 0.000 description 3
- 239000002516 radical scavenger Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 2
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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]
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13696098 | 1998-05-19 | ||
| PCT/JP1999/002572 WO1999059998A1 (fr) | 1998-05-19 | 1999-05-17 | DERIVES DE PYRAZOLO[1,5-a]PYRIMIDINE |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20005820L NO20005820L (no) | 2000-11-17 |
| NO20005820D0 NO20005820D0 (no) | 2000-11-17 |
| NO317303B1 true NO317303B1 (no) | 2004-10-04 |
Family
ID=15187527
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20005820A NO317303B1 (no) | 1998-05-19 | 2000-11-17 | Pyrazolo[1,5-a]pyrimidin-derivater |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6372749B1 (fr) |
| EP (1) | EP1081149B1 (fr) |
| JP (1) | JP4058587B2 (fr) |
| KR (1) | KR100391398B1 (fr) |
| CN (1) | CN1117093C (fr) |
| AT (1) | ATE236166T1 (fr) |
| AU (1) | AU751337B2 (fr) |
| CA (1) | CA2331468C (fr) |
| DE (1) | DE69906511T2 (fr) |
| NO (1) | NO317303B1 (fr) |
| WO (1) | WO1999059998A1 (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1368306B1 (fr) * | 2001-01-18 | 2013-01-16 | Welichem Biotech Inc. | Nouveaux derives de 1,2-diphenylethene pour le traitement de maladies immunes |
| HUP0400891A2 (en) * | 2004-04-29 | 2006-04-28 | Janos Szolcsanyi | 7h-pyrrolo[2,3-d]pyrimidine derivatives, their pharmaceutically acceptable salts, pharmaceutical compositions containing them and process for the production of the compounds |
| WO2013026942A1 (fr) * | 2011-08-25 | 2013-02-28 | The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin | Agents de liaison à la tubuline |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2585462B2 (ja) | 1989-10-25 | 1997-02-26 | 株式会社大塚製薬工場 | ピラゾロ［１，５―ａ］ピリミジン誘導体 |
| JPH07309872A (ja) | 1994-03-24 | 1995-11-28 | Otsuka Pharmaceut Factory Inc | 縮環ピリミジン誘導体及び鎮痛剤 |
| JP3252189B2 (ja) | 1994-06-21 | 2002-01-28 | 株式会社大塚製薬工場 | ピラゾロ〔１，５−ａ〕ピリミジン誘導体 |
| JP3163413B2 (ja) | 1994-06-21 | 2001-05-08 | 株式会社大塚製薬工場 | 鎮痛剤 |
| JP3163412B2 (ja) | 1994-06-21 | 2001-05-08 | 株式会社大塚製薬工場 | ピラゾロ〔１，５−ａ〕ピリミジン誘導体 |
| DE69614102T2 (de) | 1995-04-10 | 2002-03-21 | Otsuka Pharma Co Ltd | Pyrazol[1,5-a]pyrimidin derivate |
| JP3204877B2 (ja) | 1995-06-08 | 2001-09-04 | 株式会社エルモ社 | 資料提示装置 |
| CA2206080A1 (fr) | 1995-09-28 | 1997-04-03 | Otsuka Pharmaceutical Factory, Inc. | Analgesiques |
| JPH10101671A (ja) * | 1996-08-08 | 1998-04-21 | Otsuka Pharmaceut Factory Inc | 一酸化窒素合成酵素阻害剤 |
| JPH10114774A (ja) | 1996-08-20 | 1998-05-06 | Otsuka Pharmaceut Factory Inc | 一酸化窒素合成酵素阻害剤 |
-
1999
- 1999-05-17 AT AT99919634T patent/ATE236166T1/de not_active IP Right Cessation
- 1999-05-17 WO PCT/JP1999/002572 patent/WO1999059998A1/fr active IP Right Grant
- 1999-05-17 CA CA002331468A patent/CA2331468C/fr not_active Expired - Fee Related
- 1999-05-17 US US09/700,764 patent/US6372749B1/en not_active Expired - Fee Related
- 1999-05-17 JP JP2000549616A patent/JP4058587B2/ja not_active Expired - Fee Related
- 1999-05-17 AU AU37320/99A patent/AU751337B2/en not_active Ceased
- 1999-05-17 CN CN99805673A patent/CN1117093C/zh not_active Expired - Fee Related
- 1999-05-17 DE DE69906511T patent/DE69906511T2/de not_active Expired - Fee Related
- 1999-05-17 EP EP99919634A patent/EP1081149B1/fr not_active Expired - Lifetime
- 1999-05-17 KR KR10-2000-7012981A patent/KR100391398B1/ko not_active IP Right Cessation
-
2000
- 2000-11-17 NO NO20005820A patent/NO317303B1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO20005820L (no) | 2000-11-17 |
| CN1117093C (zh) | 2003-08-06 |
| US6372749B1 (en) | 2002-04-16 |
| CA2331468C (fr) | 2005-06-28 |
| CN1299362A (zh) | 2001-06-13 |
| KR100391398B1 (ko) | 2003-07-12 |
| EP1081149A1 (fr) | 2001-03-07 |
| JP4058587B2 (ja) | 2008-03-12 |
| DE69906511T2 (de) | 2004-01-29 |
| KR20010034871A (ko) | 2001-04-25 |
| DE69906511D1 (de) | 2003-05-08 |
| AU751337B2 (en) | 2002-08-15 |
| EP1081149A4 (fr) | 2001-12-19 |
| NO20005820D0 (no) | 2000-11-17 |
| AU3732099A (en) | 1999-12-06 |
| EP1081149B1 (fr) | 2003-04-02 |
| CA2331468A1 (fr) | 1999-11-25 |
| WO1999059998A1 (fr) | 1999-11-25 |
| ATE236166T1 (de) | 2003-04-15 |
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