WO1997032847A1 - Derives de pyrrolidone - Google Patents
Derives de pyrrolidone Download PDFInfo
- Publication number
- WO1997032847A1 WO1997032847A1 PCT/JP1997/000627 JP9700627W WO9732847A1 WO 1997032847 A1 WO1997032847 A1 WO 1997032847A1 JP 9700627 W JP9700627 W JP 9700627W WO 9732847 A1 WO9732847 A1 WO 9732847A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- protein phosphatase
- formula
- acid
- protein
- Prior art date
Links
- 150000004040 pyrrolidinones Chemical class 0.000 title claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 201000010099 disease Diseases 0.000 claims abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 claims description 14
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229940116193 Protein phosphatase inhibitor Drugs 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 239000003934 phosphoprotein phosphatase inhibitor Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract description 4
- 239000003018 immunosuppressive agent Substances 0.000 abstract description 3
- 108090000623 proteins and genes Proteins 0.000 abstract description 3
- 102000004169 proteins and genes Human genes 0.000 abstract description 3
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- 229940125721 immunosuppressive agent Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000243 solution Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 230000030609 dephosphorylation Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- -1 3-cyano 5-hydroxy-4,5-dimethyl-2-pyrrolidone Chemical compound 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- BWCBVSHEZSMRCU-UHFFFAOYSA-N CCCCCCCCCCCCCCCC[NH+]([CH-]C(C(C)=O)=C1C)C1=C=C Chemical compound CCCCCCCCCCCCCCCC[NH+]([CH-]C(C(C)=O)=C1C)C1=C=C BWCBVSHEZSMRCU-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000011609 ammonium molybdate Substances 0.000 description 1
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 1
- 235000018660 ammonium molybdate Nutrition 0.000 description 1
- 229940010552 ammonium molybdate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- VLAPMBHFAWRUQP-UHFFFAOYSA-L molybdic acid Chemical compound O[Mo](O)(=O)=O VLAPMBHFAWRUQP-UHFFFAOYSA-L 0.000 description 1
- NDSQLYUWCXRSCB-UHFFFAOYSA-N n-hexadecyl-3-oxobutanamide Chemical compound CCCCCCCCCCCCCCCCNC(=O)CC(C)=O NDSQLYUWCXRSCB-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/44—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members
Definitions
- the present invention relates to a pyridone derivative, and more particularly to a pyrrolidone derivative having a protein phosphatase inhibitory action.
- Phosphorylation and dephosphorylation of proteins are one of the basic regulatory mechanisms of biological functions. Among them, many agents that inhibit protein kinases have been reported as antitumor agents. However, little has been reported on inhibitors of protein phosphatase, which also plays an essential role in cell growth. Protein dephosphorylation, like phosphorylation, plays a so-called “switch” role in protein activity, and it has recently been clearly shown that protein dephosphorylation controls the activity and inactivity of proteins in vivo. It is becoming.
- the present invention provides a compound represented by the formula (I):
- R 1 represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms
- R 2 represents a cyano group or an acetyl group
- an alkyl group having 1 to 20 carbon atoms is a linear or branched alkyl group having 1 to 20 carbon atoms, such as a methyl group, an ethyl group, and a propyl group. And isopropyl, butyl, hexyl, hexadecyl, and octadecyl.
- the compound of the present invention represented by the formula (I) can be synthesized by the following method. That is, according to the method described in Journal of the American's Chemical Society [J. Am. Chem. Soc. Vol. 81, p. 4355 (1959)], 2,3-dioxobutane And expression
- the compound can be synthesized by treating a compound obtained by condensing the compound represented by the formula with an acid.
- the acid used at this time include mineral acids such as hydrochloric acid, hydrobromic acid, nitric acid, and sulfuric acid, and sulfonic acids such as 10-camphorsulfonic acid, p-toluenesulfonic acid, and methanesulfonic acid. it can.
- the acid treatment may be performed in a solvent, and a solvent such as dioxane, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, methylene chloride, chloroform, acetone, toluene, benzene and the like can be used as the solvent.
- a solvent such as dioxane, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, methylene chloride, chloroform, acetone, toluene, benzene and the like can be used as the solvent.
- tablets, pills, capsules, granules, solutions, emulsions, and suspensions can be prepared by using the compound as it is or by formulating it according to a conventional method. It can be prepared as an injection or the like and administered orally or parenterally.
- Dosage should be administered to adult patients in the range of l to 1000 mg for oral administration and 0.01 to 10 Omg for parenteral administration once to several times a day. Can be. This dosage can be appropriately increased or decreased depending on the type of the disease, the age, weight, and symptoms of the patient.
- the compound was prepared by dissolving in dimethyl sulfoxide.
- Human cell-derived protein phosphatase was prepared using Escherichia coli transfected with VHR gene.
- the protein tyrosine phosphatase CD45 was prepared from the cell membrane of the cultured cell Ba11-1.
- the compound of the present invention inhibits protein phosphatase Since it has an action, it is useful as a therapeutic agent for diseases caused by protein phosphatase, such as an antitumor agent, an immunosuppressant, and a therapeutic agent for diabetes.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Dérivés de pyrrolidone représentés par la formule générale (I), dans laquelle R1 représente hydrogène ou alkyle C¿1-20 et R?2 représente cyano ou acétyle. Ils sont efficaces en tant que remèdes contre les maladies induites par la protéine déphosphorylase, à titre d'agent antitumoral, agent immunodépresseurs et médicament contre le diabète.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU18128/97A AU1812897A (en) | 1996-03-04 | 1997-03-03 | Pyrrolidone derivatives |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP4526296 | 1996-03-04 | ||
JP8/45262 | 1996-03-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1997032847A1 true WO1997032847A1 (fr) | 1997-09-12 |
Family
ID=12714386
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1997/000627 WO1997032847A1 (fr) | 1996-03-04 | 1997-03-03 | Derives de pyrrolidone |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU1812897A (fr) |
WO (1) | WO1997032847A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2583678A2 (fr) | 2004-06-24 | 2013-04-24 | Novartis Vaccines and Diagnostics, Inc. | Immunopotentiateurs de petites molécules et dosages pour leur détection |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0317057A (ja) * | 1989-06-15 | 1991-01-25 | Fujisawa Pharmaceut Co Ltd | 新規5員環複素環化合物 |
-
1997
- 1997-03-03 AU AU18128/97A patent/AU1812897A/en not_active Abandoned
- 1997-03-03 WO PCT/JP1997/000627 patent/WO1997032847A1/fr active Application Filing
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0317057A (ja) * | 1989-06-15 | 1991-01-25 | Fujisawa Pharmaceut Co Ltd | 新規5員環複素環化合物 |
Non-Patent Citations (1)
Title |
---|
CHEM. BER., Vol. 108, No. 10, (1975), ROEBER, HUBERT et al., "Kondensation von 1,2-Diketonen mit 2-Cyanacetamid", p. 3262-3270. * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2583678A2 (fr) | 2004-06-24 | 2013-04-24 | Novartis Vaccines and Diagnostics, Inc. | Immunopotentiateurs de petites molécules et dosages pour leur détection |
Also Published As
Publication number | Publication date |
---|---|
AU1812897A (en) | 1997-09-22 |
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