SI9300616A - Enzyme inhibitors - Google Patents
Enzyme inhibitors Download PDFInfo
- Publication number
- SI9300616A SI9300616A SI9300616A SI9300616A SI9300616A SI 9300616 A SI9300616 A SI 9300616A SI 9300616 A SI9300616 A SI 9300616A SI 9300616 A SI9300616 A SI 9300616A SI 9300616 A SI9300616 A SI 9300616A
- Authority
- SI
- Slovenia
- Prior art keywords
- isothiourea
- ethyl
- methyl
- amino
- group
- Prior art date
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- 239000002532 enzyme inhibitor Substances 0.000 title description 2
- 238000002360 preparation method Methods 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 36
- 150000002541 isothioureas Chemical class 0.000 claims abstract description 31
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims abstract description 29
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims abstract description 29
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 6
- 230000008901 benefit Effects 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 69
- 229910052717 sulfur Inorganic materials 0.000 claims description 59
- -1 2-amino-4,5-dimethylthiazole S- (2- (1H-pyrrol-1-yl) ethyl) isothiourea S- (3-hydroxypropyl) isothiourea S- (2- (phenyl) ethyl) isothiourea Chemical compound 0.000 claims description 57
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 23
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 229910052698 phosphorus Inorganic materials 0.000 claims description 13
- 102000004127 Cytokines Human genes 0.000 claims description 12
- 108090000695 Cytokines Proteins 0.000 claims description 12
- 239000004201 L-cysteine Substances 0.000 claims description 12
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 12
- 125000001246 bromo group Chemical group Br* 0.000 claims description 12
- 229960002433 cysteine Drugs 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 8
- NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical compound N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- 208000001953 Hypotension Diseases 0.000 claims description 7
- 206010040070 Septic Shock Diseases 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 230000036543 hypotension Effects 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 230000036303 septic shock Effects 0.000 claims description 7
- 230000009885 systemic effect Effects 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- VFIZBHJTOHUOEK-UHFFFAOYSA-N s-ethylisothiourea Chemical compound CCSC(N)=N VFIZBHJTOHUOEK-UHFFFAOYSA-N 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 230000001939 inductive effect Effects 0.000 claims description 5
- 230000004968 inflammatory condition Effects 0.000 claims description 5
- 239000004615 ingredient Substances 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 5
- 206010062016 Immunosuppression Diseases 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 229960003767 alanine Drugs 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- GTRLQRHWPXEBLF-UHFFFAOYSA-N benzyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1 GTRLQRHWPXEBLF-UHFFFAOYSA-N 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 230000001506 immunosuppresive effect Effects 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- XSSNABKEYXKKMK-UHFFFAOYSA-N s-isopropyl-isothiourea Chemical compound CC(C)SC(N)=N XSSNABKEYXKKMK-UHFFFAOYSA-N 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- NKNLCJKCBKBJNG-UHFFFAOYSA-N 2-(4-ethoxy-3-methoxyphenyl)ethyl carbamimidothioate Chemical compound CCOC1=CC=C(CCSC(N)=N)C=C1OC NKNLCJKCBKBJNG-UHFFFAOYSA-N 0.000 claims description 3
- GDFAOVXKHJXLEI-VKHMYHEASA-N N-methyl-L-alanine Chemical compound C[NH2+][C@@H](C)C([O-])=O GDFAOVXKHJXLEI-VKHMYHEASA-N 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- JLTDDFXRNCSHEV-UHFFFAOYSA-N methyl N'-[[3-[[[amino(methylsulfanyl)methylidene]amino]methyl]phenyl]methyl]carbamimidothioate Chemical compound CSC(N)=NCC1=CC=CC(CN=C(N)SC)=C1 JLTDDFXRNCSHEV-UHFFFAOYSA-N 0.000 claims description 3
- JKHAGQZCIAFTOX-UHFFFAOYSA-N propyl carbamimidothioate Chemical compound CCCSC(N)=N JKHAGQZCIAFTOX-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- DVOOXRTYGGLORL-VKHMYHEASA-N (2r)-2-(methylamino)-3-sulfanylpropanoic acid Chemical compound CN[C@@H](CS)C(O)=O DVOOXRTYGGLORL-VKHMYHEASA-N 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- REGFWZVTTFGQOJ-UHFFFAOYSA-N 4,5-dihydro-1,3-thiazol-2-amine Chemical compound NC1=NCCS1 REGFWZVTTFGQOJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000004450 alkenylene group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004419 alkynylene group Chemical group 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- SDDKIZNHOCEXTF-UHFFFAOYSA-N methyl carbamimidothioate Chemical compound CSC(N)=N SDDKIZNHOCEXTF-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- XTSVKUJYTUPYRJ-HMLOAIDSSA-N S-(2-aminoethyl)isothiourea Chemical group O([C@]12CN(C3[C@@]4(O)[C@]5(O)[C@@]6(O)[C@@H](OC)[C@@H]([C@H](C5)OC)C[C@H]6[C@@]3([C@@H]1C4)[C@@H](OC)CC2)CC)C(=O)C1=CC=CC=C1NC(C)=O XTSVKUJYTUPYRJ-HMLOAIDSSA-N 0.000 claims 1
- AMNPXXIGUOKIPP-UHFFFAOYSA-N [4-(carbamothioylamino)phenyl]thiourea Chemical compound NC(=S)NC1=CC=C(NC(N)=S)C=C1 AMNPXXIGUOKIPP-UHFFFAOYSA-N 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- 239000000243 solution Substances 0.000 description 44
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 26
- 239000007787 solid Substances 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
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- 239000000872 buffer Substances 0.000 description 13
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- 238000000921 elemental analysis Methods 0.000 description 12
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- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole 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
- C07D277/18—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/18—Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Communicable Diseases (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929224948A GB9224948D0 (en) | 1992-11-27 | 1992-11-27 | Nitric oxide synthase inhibitors |
| GB939315159A GB9315159D0 (en) | 1993-07-22 | 1993-07-22 | Nitric oxide synthase inhibitors |
| GB939319663A GB9319663D0 (en) | 1993-09-23 | 1993-09-23 | Enzyme inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI9300616A true SI9300616A (en) | 1994-06-30 |
Family
ID=27266488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI9300616A SI9300616A (en) | 1992-11-27 | 1993-11-26 | Enzyme inhibitors |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0670720A1 (de) |
| JP (1) | JPH08503940A (de) |
| CN (1) | CN1095710A (de) |
| AU (1) | AU5533094A (de) |
| IL (1) | IL107771A0 (de) |
| SI (1) | SI9300616A (de) |
| WO (1) | WO1994012165A2 (de) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL180081B1 (pl) * | 1993-08-12 | 2000-12-29 | Astra Ab | Nowe pochodne amidyny i sposób ich wytwarzania PL PL PL PL PL PL PL |
| KR100342275B1 (ko) | 1993-10-21 | 2002-12-05 | 지.디. 썰 엘엘씨 | 산화질소신타제저해제로서유용한아미디노유도체 |
| CA2188680A1 (en) * | 1994-05-07 | 1996-01-25 | James Edwin Macdonald | Bicyclic amidine derivatives as inhibitors of nitric oxide synthetase |
| GB9418912D0 (en) * | 1994-09-20 | 1994-11-09 | Fisons Corp | Pharmaceutically active compounds |
| AU4149696A (en) * | 1994-11-15 | 1996-06-06 | Merck & Co., Inc. | Substituted heterocycles as inhibitors of nitric oxide synthase |
| AU4515896A (en) * | 1994-12-12 | 1996-07-03 | Merck & Co., Inc. | Substituted 2-acylamino-pyridines as inhibitors of nitric oxide synthase |
| JPH08333258A (ja) | 1994-12-14 | 1996-12-17 | Japan Tobacco Inc | チアジン又はチアゼピン誘導体及びそれら化合物を含有してなる一酸化窒素合成酵素阻害剤 |
| FR2728261A1 (fr) * | 1994-12-14 | 1996-06-21 | Japan Tobacco Inc | Derives de thiazine ou de thiazepine utiles comme inhibiteurs de la no-synthetase |
| DE4444930A1 (de) * | 1994-12-16 | 1996-06-27 | Cassella Ag | 2-Amino-1,3-thiazepine und deren Verwendung als Hemmstoffe der Stickstoffmonoxid-Synthase |
| WO1996021445A1 (en) * | 1995-01-13 | 1996-07-18 | The General Hospital Corporation | Methods of inhibiting neurodegenerative diseases |
| TW397812B (en) * | 1995-02-11 | 2000-07-11 | Astra Ab | Bicyclic isothiourea derivatives useful in therapy |
| FR2730733B1 (fr) * | 1995-02-17 | 1997-07-04 | Hoechst Lab | Nouveaux derives nitro-ethyleniques soufres et leurs applications en tant qu'inhibiteurs de no-synthase |
| US5674907A (en) * | 1995-03-24 | 1997-10-07 | Children's Hospital Medical Center | Mercapto derivatives as inhibitors of nitric oxide synthase |
| US5929063A (en) * | 1995-03-24 | 1999-07-27 | Children's Hospital Medical Center | Mercapto and seleno derivatives as inhibitors of nitric oxide synthase |
| GB9506188D0 (en) * | 1995-03-27 | 1995-05-17 | Fujisawa Pharmaceutical Co | Amidine derivatives |
| DE69629364T2 (de) * | 1995-04-20 | 2004-06-09 | G.D. Searle & Co., Chicago | Zyclische amidino mittel als stickstoffoxid-synthase inhibitoren |
| US5908842A (en) * | 1995-12-08 | 1999-06-01 | Merck & Co., Inc. | Substituted 2-acylamino-pyridines as inhibitors of nitric oxide synthase |
| US5945408A (en) * | 1996-03-06 | 1999-08-31 | G.D. Searle & Co. | Hydroxyanidino derivatives useful as nitric oxide synthase inhibitors |
| US6160000A (en) * | 1996-12-23 | 2000-12-12 | Merck & Co., Inc. | Antidiabetic agents based on aryl and heteroarylacetic acids |
| US6090839A (en) * | 1996-12-23 | 2000-07-18 | Merck & Co., Inc. | Antidiabetic agents |
| US5981556A (en) * | 1997-07-22 | 1999-11-09 | G.D. Searle & Co. | 1,3-diazolino and 1,3-diazolidino heterocycles as useful nitric oxide synthase inhibitors |
| JP2002509555A (ja) * | 1998-04-06 | 2002-03-26 | 藤沢薬品工業株式会社 | 新規用途 |
| US6552052B2 (en) | 1998-06-10 | 2003-04-22 | Monsanto/G.D. Searle | Pyrrolo[2,1-c][1,2,4] thiadiazoles and Pyrollo[2,1-c][1,12,4]oxadiazoles useful as nitric oxide synthase inhibitors |
| CA2333691A1 (en) | 1998-06-10 | 1999-12-16 | G.D. Searle & Co. | Heterobicyclic and tricyclic nitric oxide synthase inhibitors |
| GB9903404D0 (en) | 1999-02-16 | 1999-04-07 | Angiogene Pharm Ltd | Methods of treatment and compositions useful for the treatment of diseases involving angiogenesis |
| ES2449194T3 (es) * | 2000-01-19 | 2014-03-18 | Cadila Healthcare Limited | Compuestos que tienen actividades hipolipidémica e hipocolesterolémica, procedimiento para su preparación y composiciones farmacéuticas que los contienen |
| GEP20094625B (en) | 2000-03-24 | 2009-03-10 | Pharmacia Corp | Amidino compound and salts thereof useful as nitric oxide synthase inhibitors |
| ATE296627T1 (de) | 2000-03-31 | 2005-06-15 | Univ Medisch Centrum Utrecht | Verwendung von 2-iminobiotin zur herstellung eines arzneimittels zur prävention und / oder therapie von komplikationen bei neugeborenen, die während der geburt entstanden sind |
| US7087633B2 (en) | 2000-03-31 | 2006-08-08 | Universitair Medisch Centrum | Method for treating perinatal asphyxia in a human or animal neonate |
| US6956131B2 (en) | 2000-04-13 | 2005-10-18 | Pharmacia Corporation | 2-amino-3, 4 heptenoic compounds useful as nitric oxide synthase inhibitors |
| AR032318A1 (es) | 2000-04-13 | 2003-11-05 | Pharmacia Corp | Compuesto derivado halogenado del acido 2-amino-5,6 heptenoico; composicion farmaceutica que lo comprende y su uso en la fabricacion de un medicamento util como inhibidor de la oxido nitrico sintetasa |
| AR034120A1 (es) | 2000-04-13 | 2004-02-04 | Pharmacia Corp | Compuesto derivado halogenado del acido 2-amino-4,5 heptenoico, composicion farmaceutica que lo comprende y el uso de dicho compuesto y dicha composicion en la fabricacion de un medicamento para inhibir o modular la sintesis de acido nitrico |
| US6545170B2 (en) | 2000-04-13 | 2003-04-08 | Pharmacia Corporation | 2-amino-5, 6 heptenoic acid derivatives useful as nitric oxide synthase inhibitors |
| AR030416A1 (es) | 2000-04-13 | 2003-08-20 | Pharmacia Corp | COMPUESTO DERIVADO HALOGENADO DEL ACIDO 2-AMINO-3,4 HEPTENOICO, COMPOSICION FARMACEUTICA QUE LO COMPRENDE Y SU USO EN LA FABRICACION DE UN MEDICAMENTO uTIL COMO INHIBIDOR DE LA OXIDO NITRICO SINTETASA |
| US6787668B2 (en) | 2000-04-13 | 2004-09-07 | Pharmacia Corporation | 2-amino-4,5 heptenoic acid derivatives useful as nitric oxide synthase inhibitors |
| FR2832152A1 (fr) * | 2001-11-09 | 2003-05-16 | Aventis Pharma Sa | Utilisation de derives de 2-amino-thiazoline comme inhibiteurs de no-synthase inductible |
| FR2810037B1 (fr) * | 2000-06-09 | 2004-04-23 | Aventis Pharma Sa | Utilisation de derives de 2-aminothiazoline comme inhibiteurs de no-synthase inductible |
| US6420566B2 (en) | 2000-06-09 | 2002-07-16 | Aventis Pharma S.A. | Pharmaceutical compositions containing a 4, 5-dihydro-1, 3-thiazol-2-ylamine derivative, novel derivatives and preparation thereof |
| US6451821B1 (en) | 2000-06-09 | 2002-09-17 | Aventis Pharma S.A. | Use of 2-aminothiazoline derivatives as inhibitors of inducible no-synthase |
| FR2810036B1 (fr) * | 2000-06-09 | 2004-04-23 | Aventis Pharma Sa | Derives de 4,5-dihydro-1,3-thiazol-2-ylamine, leur preparation et les compositions phamarceutiques les contenant |
| US6344473B1 (en) | 2000-08-07 | 2002-02-05 | G.D. Searle & Co. | Imidazoles useful as nitric oxide synthase inhibitors |
| US7012098B2 (en) | 2001-03-23 | 2006-03-14 | Pharmacia Corporation | Inhibitors of inducible nitric oxide synthase for chemoprevention and treatment of cancers |
| PT1446393E (pt) | 2001-11-09 | 2006-05-31 | Aventis Pharma Sa | Derivados de 2-amino-tiazolina e sua utilizacao como inibidores da sintase de no indutivel |
| FR2832150B1 (fr) * | 2001-11-09 | 2004-07-16 | Aventis Pharma Sa | Utilisation de derives de 2-amino-4-pyridylmethyl-thiazoline comme inhibiteurs de no-synthase inductible |
| FR2832151B1 (fr) * | 2001-11-09 | 2004-12-17 | Aventis Pharma Sa | Utilisation de derives de 2-amino-4-heteroarylethyl-thiazoline comme inhibiteurs de no-synthase inductible |
| JP4342309B2 (ja) | 2001-11-09 | 2009-10-14 | アベンティス・ファーマ・ソシエテ・アノニム | 誘導型no−シンターゼ阻害剤としての2−アミノ−4−ピリジルメチル−チアゾリン誘導体の使用 |
| ES2250731T3 (es) | 2001-11-09 | 2006-04-16 | Aventis Pharma S.A. | Derivados de 2-amino-4-heteroariletil tiazolina y su utilizacion como inhibidores de no-sintasa inductible. |
| CA2628074C (en) | 2005-10-25 | 2014-01-14 | Shionogi & Co., Ltd. | Aminodihydrothiazine derivative |
| US20090186854A1 (en) * | 2006-03-23 | 2009-07-23 | Meditor Pharmaceuticals Ltd. | S-alkylisothiouronium derivatives for the treatment of inflammatory diseases |
| JP5383484B2 (ja) | 2007-04-24 | 2014-01-08 | 塩野義製薬株式会社 | 環式基で置換されたアミノジヒドロチアジン誘導体 |
| US8653067B2 (en) | 2007-04-24 | 2014-02-18 | Shionogi & Co., Ltd. | Pharmaceutical composition for treating Alzheimer's disease |
| KR101324426B1 (ko) | 2008-06-13 | 2013-10-31 | 시오노기세야쿠 가부시키가이샤 | β 세크레타제 저해 작용을 갖는 황 함유 복소환 유도체 |
| CN101372471B (zh) * | 2008-10-08 | 2010-12-22 | 中国科学院化学研究所 | 烷基异脲类化合物及其类似物的新用途 |
| CN102186841A (zh) | 2008-10-22 | 2011-09-14 | 盐野义制药株式会社 | 具有bace1抑制活性的2-氨基嘧啶-4-酮及2-氨基吡啶衍生物 |
| EP2415756A4 (de) | 2009-03-31 | 2012-08-29 | Shionogi & Co | Isothioharnstoffderivate oder isoharnstoffderivate mit bace1-hemmender wirkung |
| MX2012006491A (es) | 2009-12-11 | 2012-07-03 | Shionogi & Co | Derivados de oxazina. |
| EP2634188A4 (de) | 2010-10-29 | 2014-05-07 | Shionogi & Co | Kondensiertes aminodihydropyrimidinderivat |
| JP5816630B2 (ja) | 2010-10-29 | 2015-11-18 | 塩野義製薬株式会社 | ナフチリジン誘導体 |
| US8883779B2 (en) | 2011-04-26 | 2014-11-11 | Shinogi & Co., Ltd. | Oxazine derivatives and a pharmaceutical composition for inhibiting BACE1 containing them |
| EP2912035A4 (de) | 2012-10-24 | 2016-06-15 | Shionogi & Co | Dihydrooxazin- oder oxazepinderivate mit bace1-hemmender wirkung |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1178242A (en) * | 1966-02-05 | 1970-01-21 | Wellcome Found | Novel Biologically Active Bis-Isothioureas |
| US3790600A (en) * | 1972-04-06 | 1974-02-05 | Uniroyal Inc | 2-(3-benzo(b)thenyl)-2-thiopseudourea and its pharmaceutically acceptable salts |
| US3954982A (en) * | 1972-04-20 | 1976-05-04 | Smith Kline & French Laboratories Limited | Pharmaceutical compositions and method of inhibiting H-1 and H-2 histamine receptors |
| ZA771408B (en) * | 1976-03-29 | 1978-04-26 | Smith Kline French Lab | Pharmaceutical compositions |
| US4208430A (en) * | 1979-03-15 | 1980-06-17 | Smithkline Corporation | Pharmaceutical compositions and method of inhibiting phenylethanolamine N-methyltransferase |
| US4262125A (en) * | 1979-07-23 | 1981-04-14 | American Home Products Corporation | (1H-Imidazol-5-ylmethyl)isothioureas |
| EP0245669B1 (de) * | 1986-05-14 | 1993-12-01 | Medopharm Arzneimittelwerk Dr. Zillich GmbH & Co. | Pharmazeutisches Präparat zur Verhütung der Schädigung lebender Zellen durch freie Radikale, beziehungsweise zur Erhöhung der Wirksamkeit von organischen Schwefelverbindungen und Verfahren zur Erhöhung der Lebensdauer isolierter Organe |
| GB8916947D0 (en) * | 1989-07-25 | 1989-09-13 | Smith Kline French Lab | Medicaments |
| CA2066728C (en) * | 1989-09-19 | 2001-12-25 | Jan K. Hellstrand | Anti-tumor preparation comprising interleukin-2 and histamine, analogs thereof or h2-receptor agonists |
| ATE191847T1 (de) * | 1991-12-16 | 2000-05-15 | Univ Washington | Verwendung von aminoguamidin zur herstellung eines arzneimittels zur unterdrückung der stickoxidbildung |
| KR100892685B1 (ko) * | 2007-11-09 | 2009-04-15 | 주식회사 하이닉스반도체 | Eaic 시스템 |
-
1993
- 1993-11-26 EP EP94900266A patent/EP0670720A1/de not_active Withdrawn
- 1993-11-26 JP JP6512923A patent/JPH08503940A/ja active Pending
- 1993-11-26 CN CN93121643A patent/CN1095710A/zh active Pending
- 1993-11-26 AU AU55330/94A patent/AU5533094A/en not_active Abandoned
- 1993-11-26 SI SI9300616A patent/SI9300616A/sl unknown
- 1993-11-26 IL IL10777193A patent/IL107771A0/xx unknown
- 1993-11-26 WO PCT/GB1993/002437 patent/WO1994012165A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| IL107771A0 (en) | 1994-02-27 |
| WO1994012165A2 (en) | 1994-06-09 |
| AU5533094A (en) | 1994-06-22 |
| JPH08503940A (ja) | 1996-04-30 |
| CN1095710A (zh) | 1994-11-30 |
| WO1994012165A3 (en) | 1994-12-08 |
| EP0670720A1 (de) | 1995-09-13 |
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