UA62939C2 - Похідне 2-ціаноіміноімідазолу, фармацевтична композиція та спосіб одержання сполуки - Google Patents
Похідне 2-ціаноіміноімідазолу, фармацевтична композиція та спосіб одержання сполуки Download PDFInfo
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- UA62939C2 UA62939C2 UA99031702A UA99031702A UA62939C2 UA 62939 C2 UA62939 C2 UA 62939C2 UA 99031702 A UA99031702 A UA 99031702A UA 99031702 A UA99031702 A UA 99031702A UA 62939 C2 UA62939 C2 UA 62939C2
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- Prior art keywords
- alkyl
- substituted
- formula
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- compounds
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- UCPBYQVLXUIDCK-UHFFFAOYSA-N imidazol-2-ylidenecyanamide Chemical class N#CN=C1N=CC=N1 UCPBYQVLXUIDCK-UHFFFAOYSA-N 0.000 title abstract description 3
- 230000005764 inhibitory process Effects 0.000 title description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 143
- -1 6,7-dihydro-5H-cyclopentapyridinyl Chemical group 0.000 claims abstract description 68
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 22
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 21
- 125000003118 aryl group Chemical group 0.000 claims abstract description 20
- 229910052757 nitrogen Chemical group 0.000 claims abstract description 19
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 14
- 125000005843 halogen group Chemical group 0.000 claims abstract description 13
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 12
- 239000001301 oxygen Substances 0.000 claims abstract description 12
- 239000011593 sulfur Chemical group 0.000 claims abstract description 12
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 9
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims abstract description 9
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 8
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract 3
- 239000002253 acid Substances 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 150000007513 acids Chemical class 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000003277 amino group Chemical group 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 11
- 239000000654 additive Substances 0.000 claims description 9
- 125000002541 furyl group Chemical group 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 239000012442 inert solvent Substances 0.000 claims description 8
- 230000000996 additive effect Effects 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 206010003645 Atopy Diseases 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 230000009466 transformation Effects 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 229940126601 medicinal product Drugs 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- 238000010306 acid treatment Methods 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 abstract description 9
- 108090000695 Cytokines Proteins 0.000 abstract description 9
- 239000001257 hydrogen Substances 0.000 abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 9
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 2
- 150000002431 hydrogen Chemical group 0.000 abstract 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 abstract 1
- 125000000815 N-oxide group Chemical group 0.000 abstract 1
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 abstract 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
- 239000000543 intermediate Substances 0.000 description 88
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 239000000203 mixture Substances 0.000 description 56
- 239000002904 solvent Substances 0.000 description 50
- 239000000243 solution Substances 0.000 description 37
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 28
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 28
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000003480 eluent Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 13
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 208000012657 Atopic disease Diseases 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 208000027866 inflammatory disease Diseases 0.000 description 6
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- 150000003254 radicals Chemical class 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
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- 125000006239 protecting group Chemical group 0.000 description 5
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
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- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 3
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- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/48—Nitrogen atoms not forming part of a nitro radical with acyclic hydrocarbon or substituted acyclic hydrocarbon radicals, attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP96202749 | 1996-10-02 | ||
| PCT/EP1997/005322 WO1998014432A1 (en) | 1996-10-02 | 1997-09-24 | Pde iv inhibiting 2-cyanoiminoimidazole derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA62939C2 true UA62939C2 (uk) | 2004-01-15 |
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| UA99031702A UA62939C2 (uk) | 1996-10-02 | 1997-09-24 | Похідне 2-ціаноіміноімідазолу, фармацевтична композиція та спосіб одержання сполуки |
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| EP (1) | EP0934280B1 (de) |
| JP (1) | JP3068208B2 (de) |
| KR (1) | KR100520002B1 (de) |
| CN (1) | CN1106387C (de) |
| AR (1) | AR008875A1 (de) |
| AT (1) | ATE236884T1 (de) |
| AU (1) | AU719561B2 (de) |
| BG (1) | BG64278B1 (de) |
| BR (1) | BR9712256B1 (de) |
| CA (1) | CA2267322C (de) |
| CY (1) | CY2380B1 (de) |
| CZ (1) | CZ297474B6 (de) |
| DE (1) | DE69720757T2 (de) |
| DK (1) | DK0934280T3 (de) |
| EE (1) | EE03825B1 (de) |
| ES (1) | ES2196308T3 (de) |
| HK (1) | HK1020344A1 (de) |
| HU (1) | HU225158B1 (de) |
| IL (2) | IL129298A0 (de) |
| MY (1) | MY116980A (de) |
| NO (1) | NO312960B1 (de) |
| NZ (1) | NZ334971A (de) |
| PL (1) | PL194673B1 (de) |
| PT (1) | PT934280E (de) |
| RU (1) | RU2180902C2 (de) |
| SI (1) | SI0934280T1 (de) |
| SK (1) | SK285878B6 (de) |
| TR (1) | TR199900732T2 (de) |
| UA (1) | UA62939C2 (de) |
| WO (1) | WO1998014432A1 (de) |
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| NZ507022A (en) | 1998-04-01 | 2002-06-28 | Janssen Pharmaceutica Nv | PDE IV inhibiting pyridine derivatives |
| US6953774B2 (en) | 2000-08-11 | 2005-10-11 | Applied Research Systems Ars Holding N.V. | Methods of inducing ovulation |
| KR100749794B1 (ko) * | 2001-04-19 | 2007-08-17 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 2-이미노피롤리딘 유도체 |
| CA2447618A1 (en) | 2001-05-23 | 2002-11-28 | Tanabe Seiyaku Co., Ltd. | A composition for regenerative treatment of cartilage disease |
| CN100358514C (zh) * | 2001-07-11 | 2008-01-02 | 日研化学株式会社 | 过敏性眼疾病治疗剂 |
| TWI221838B (en) | 2001-08-09 | 2004-10-11 | Tanabe Seiyaku Co | Pyrazinoisoquinoline compound or naphthalene compound |
| KR101056916B1 (ko) | 2001-12-14 | 2011-08-12 | 라보라토리스 세로노 에스.에이. | 비폴리펩티드 고리에이엠피 레벨 모듈레이터를 이용한 배란유도 방법 |
| CN100439336C (zh) | 2003-02-19 | 2008-12-03 | 卫材R&D管理有限公司 | 制备环状苯甲脒衍生物的方法 |
| CA2620333A1 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| EP2258359A3 (de) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenese durch Modulation des Muscarinrezeptors mit Sabcomelin |
| EP2377530A3 (de) | 2005-10-21 | 2012-06-20 | Braincells, Inc. | Modulation von Neurogenese durch PDE-Hemmung |
| WO2007053596A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| JP2009536669A (ja) | 2006-05-09 | 2009-10-15 | ブレインセルス，インコーポレイティド | アンジオテンシン調節による神経新生 |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| US20150119399A1 (en) | 2012-01-10 | 2015-04-30 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| CA2985787A1 (en) * | 2012-06-07 | 2013-12-12 | Georgia State University Research Foundation, Inc. | Seca inhibitors and methods of making and using thereof |
| GB2533925A (en) * | 2014-12-31 | 2016-07-13 | Univ Bath | Antimicrobial compounds, compositions and methods |
| CN109438434B (zh) * | 2018-11-19 | 2021-05-04 | 华南农业大学 | 一种含噁唑环的2-氰基亚氨基噻唑烷类化合物及其制备方法和应用 |
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| JPH0784461B2 (ja) * | 1986-12-19 | 1995-09-13 | 日本バイエルアグロケム株式会社 | 殺虫性ニトロイミノ又はシアノイミノ化合物 |
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| WO1994002465A1 (en) * | 1992-07-28 | 1994-02-03 | Rhone-Poulenc Rorer Limited | INHIBITORS OF c-AMP PHOSPHODIESTERASE AND TNF |
| NZ257955A (en) * | 1992-12-02 | 1996-05-28 | Pfizer | Catechol diethers pharmaceutical compositions |
| GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| ZA945609B (en) * | 1993-07-28 | 1995-05-12 | Rhone Poulenc Rorer Ltd | [Di(ether or thioether)heteroaryl or fluoro substituted aryl] compounds |
| JPH09502170A (ja) * | 1993-08-19 | 1997-03-04 | スミスクライン・ビーチャム・コーポレイション | フェネチルアミン化合物 |
| GB9401460D0 (en) * | 1994-01-26 | 1994-03-23 | Rhone Poulenc Rorer Ltd | Compositions of matter |
| JP3056788B2 (ja) * | 1994-06-24 | 2000-06-26 | ユーロ−セルティーク，エス．エイ． | ホスホジエステラーゼｉｖの阻害化合物および阻害方法 |
| TW332201B (en) * | 1995-04-06 | 1998-05-21 | Janssen Pharmaceutica Nv | 1,3-Dihydro-1-(phenylalkyl)-2H-imidazol-2-one derivatives |
| TW375612B (en) * | 1995-04-06 | 1999-12-01 | Janssen Pharmaceutica Nv | 1,3-dihydro-2H-imidazol-2-one derivatives for the treatment of disease states related to an abnormal enzymatic or catalytic activity of phosphodiesterase type IV, preparation thereof and pharmaceutical composition containing the same |
| TW424087B (en) * | 1995-04-06 | 2001-03-01 | Janssen Pharmaceutica Nv | 1,3-dihydro-1-(phenylalkenyl)-2H-imidazol-2-one derivatives |
-
1997
- 1997-09-24 SI SI9730550T patent/SI0934280T1/xx unknown
- 1997-09-24 NZ NZ334971A patent/NZ334971A/xx not_active IP Right Cessation
- 1997-09-24 TR TR1999/00732T patent/TR199900732T2/xx unknown
- 1997-09-24 UA UA99031702A patent/UA62939C2/uk unknown
- 1997-09-24 CA CA002267322A patent/CA2267322C/en not_active Expired - Lifetime
- 1997-09-24 ES ES97910380T patent/ES2196308T3/es not_active Expired - Lifetime
- 1997-09-24 DE DE69720757T patent/DE69720757T2/de not_active Expired - Lifetime
- 1997-09-24 JP JP10516215A patent/JP3068208B2/ja not_active Expired - Lifetime
- 1997-09-24 HU HU9904063A patent/HU225158B1/hu unknown
- 1997-09-24 AU AU47792/97A patent/AU719561B2/en not_active Expired
- 1997-09-24 DK DK97910380T patent/DK0934280T3/da active
- 1997-09-24 SK SK344-99A patent/SK285878B6/sk not_active IP Right Cessation
- 1997-09-24 IL IL12929897A patent/IL129298A0/xx active IP Right Grant
- 1997-09-24 AT AT97910380T patent/ATE236884T1/de active
- 1997-09-24 RU RU99109032/04A patent/RU2180902C2/ru active
- 1997-09-24 CZ CZ0102899A patent/CZ297474B6/cs not_active IP Right Cessation
- 1997-09-24 EE EEP199900112A patent/EE03825B1/xx unknown
- 1997-09-24 PL PL97332573A patent/PL194673B1/pl unknown
- 1997-09-24 WO PCT/EP1997/005322 patent/WO1998014432A1/en active IP Right Grant
- 1997-09-24 KR KR10-1999-7001204A patent/KR100520002B1/ko not_active IP Right Cessation
- 1997-09-24 CN CN97198460A patent/CN1106387C/zh not_active Expired - Lifetime
- 1997-09-24 EP EP97910380A patent/EP0934280B1/de not_active Expired - Lifetime
- 1997-09-24 US US09/147,925 patent/US6051718A/en not_active Expired - Lifetime
- 1997-09-24 PT PT97910380T patent/PT934280E/pt unknown
- 1997-09-24 BR BRPI9712256-4A patent/BR9712256B1/pt not_active IP Right Cessation
- 1997-10-01 AR ARP970104528A patent/AR008875A1/es active IP Right Grant
- 1997-10-02 MY MYPI97004600A patent/MY116980A/en unknown
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1999
- 1999-03-01 BG BG103220A patent/BG64278B1/bg unknown
- 1999-03-30 NO NO19991560A patent/NO312960B1/no not_active IP Right Cessation
- 1999-03-31 IL IL129298A patent/IL129298A/en not_active IP Right Cessation
- 1999-11-27 HK HK99105520A patent/HK1020344A1/xx not_active IP Right Cessation
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2003
- 2003-11-04 CY CY0300074A patent/CY2380B1/xx unknown
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