HRP20000595A2 - Halogenated amidino amino acid derivatives useful as nitric oxide synthase inhibitors - Google Patents
Halogenated amidino amino acid derivatives useful as nitric oxide synthase inhibitors Download PDFInfo
- Publication number
- HRP20000595A2 HRP20000595A2 HR20000595A HRP20000595A HRP20000595A2 HR P20000595 A2 HRP20000595 A2 HR P20000595A2 HR 20000595 A HR20000595 A HR 20000595A HR P20000595 A HRP20000595 A HR P20000595A HR P20000595 A2 HRP20000595 A2 HR P20000595A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- dihydrochloride
- amino
- group
- iminoethyl
- Prior art date
Links
- -1 amidino amino Chemical class 0.000 title claims description 106
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 title description 6
- CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 77
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 62
- 229910052736 halogen Inorganic materials 0.000 claims description 56
- 150000002367 halogens Chemical class 0.000 claims description 56
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 31
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 30
- 125000001424 substituent group Chemical group 0.000 claims description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 23
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 19
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 12
- 125000005026 carboxyaryl group Chemical group 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- 150000003573 thiols Chemical class 0.000 claims description 12
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 7
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 6
- 239000004472 Lysine Substances 0.000 claims description 6
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 6
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 6
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- VUMGOHGZTFBGOB-UHFFFAOYSA-N 2-[2-aminoethyl-(2-fluoroethanimidoyl)amino]-4-sulfanylbutanoic acid dihydrochloride Chemical compound Cl.Cl.FCC(=N)N(C(CCS)C(=O)O)CCN VUMGOHGZTFBGOB-UHFFFAOYSA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- GVYDKMKZAPGDAA-SEPHDYHBSA-N (e)-2-amino-6-[(1-amino-2-fluoroethylidene)amino]hex-4-enoic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)C(N)C\C=C\CNC(=N)CF GVYDKMKZAPGDAA-SEPHDYHBSA-N 0.000 claims description 2
- QDUMYRNDUDEVMX-UHFFFAOYSA-N 2-[2-aminoethyl-(2,2-difluoroethanimidoyl)amino]-4-sulfanylbutanoic acid dihydrochloride Chemical compound Cl.Cl.FC(C(=N)N(C(CCS)C(=O)O)CCN)F QDUMYRNDUDEVMX-UHFFFAOYSA-N 0.000 claims description 2
- GAAQUMJEZCPNHH-UHFFFAOYSA-N 2-amino-6-(1-aminoethylideneamino)-5-fluorohexanoic acid;dihydrochloride Chemical compound Cl.Cl.CC(N)=NCC(F)CCC(N)C(O)=O GAAQUMJEZCPNHH-UHFFFAOYSA-N 0.000 claims description 2
- RCAYPJBOOYTTOS-UHFFFAOYSA-N 2-amino-6-[(1-amino-2-fluoroethylidene)amino]-5-cyclopropylhexanoic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)C(N)CCC(CNC(=N)CF)C1CC1 RCAYPJBOOYTTOS-UHFFFAOYSA-N 0.000 claims description 2
- ZOMRDHMTVRPEEI-UHFFFAOYSA-N 2-amino-6-[(1-amino-2-fluoroethylidene)amino]-5-methylhexanoic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)C(N)CCC(C)CNC(=N)CF ZOMRDHMTVRPEEI-UHFFFAOYSA-N 0.000 claims description 2
- 101100079984 Caenorhabditis elegans nhr-9 gene Chemical group 0.000 claims description 2
- GSEPWZMCCGDXBT-UHFFFAOYSA-N Cl.Cl.N=C(C)N(C(CCS)C(=O)O)C(CN)(F)F Chemical compound Cl.Cl.N=C(C)N(C(CCS)C(=O)O)C(CN)(F)F GSEPWZMCCGDXBT-UHFFFAOYSA-N 0.000 claims description 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 2
- 235000019766 L-Lysine Nutrition 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 6
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 6
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 6
- 125000006731 (C1-C8) thioalkoxy group Chemical group 0.000 claims 3
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- 229940079593 drug Drugs 0.000 claims 2
- 125000006833 (C1-C5) alkylene group Chemical group 0.000 claims 1
- YYIDNHWNGPOANQ-UHFFFAOYSA-N 5-amino-2-[(1-amino-2-chloro-2,2-difluoroethylidene)amino]-3-(sulfanylmethyl)pentanoic acid;dihydrochloride Chemical compound Cl.Cl.NCCC(CS)C(C(O)=O)N=C(N)C(F)(F)Cl YYIDNHWNGPOANQ-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
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- 239000000243 solution Substances 0.000 description 31
- 239000000203 mixture Substances 0.000 description 29
- 125000004432 carbon atom Chemical group C* 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- 150000002431 hydrogen Chemical class 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
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- 150000004699 copper complex Chemical class 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- 239000002158 endotoxin Substances 0.000 description 8
- MULVVEXEENBHMQ-UHFFFAOYSA-N ethyl 2-fluoroethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)CF MULVVEXEENBHMQ-UHFFFAOYSA-N 0.000 description 8
- 125000003342 alkenyl group Chemical group 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
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- 235000014852 L-arginine Nutrition 0.000 description 6
- 229930064664 L-arginine Natural products 0.000 description 6
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 6
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 6
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 6
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 150000001409 amidines Chemical group 0.000 description 6
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- 229940088710 antibiotic agent Drugs 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- WGMHMVLZFAJNOT-UHFFFAOYSA-N 1-ethoxyethylideneazanium;chloride Chemical compound [Cl-].CCOC(C)=[NH2+] WGMHMVLZFAJNOT-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
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- 239000006185 dispersion Substances 0.000 description 4
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- HILHCIBEZCWKBD-AKGZTFGVSA-N (2s)-2,6-diamino-5-fluorohexanoic acid Chemical compound NCC(F)CC[C@H](N)C(O)=O HILHCIBEZCWKBD-AKGZTFGVSA-N 0.000 description 3
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Classifications
-
- 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
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/14—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3828498A | 1998-03-11 | 1998-03-11 | |
PCT/US1999/003728 WO1999046240A2 (en) | 1998-03-11 | 1999-03-04 | Halogenated amidino amino acid derivatives useful as nitric oxide synthase inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20000595A2 true HRP20000595A2 (en) | 2001-04-30 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20000595A HRP20000595A2 (en) | 1998-03-11 | 2000-09-08 | Halogenated amidino amino acid derivatives useful as nitric oxide synthase inhibitors |
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US (1) | US6344483B1 (zh) |
EP (2) | EP1062201B1 (zh) |
JP (1) | JP2002506056A (zh) |
KR (1) | KR20010034598A (zh) |
CN (1) | CN1171861C (zh) |
AP (1) | AP2000001900A0 (zh) |
AR (1) | AR018159A1 (zh) |
AT (1) | ATE277894T1 (zh) |
AU (1) | AU746235B2 (zh) |
BG (1) | BG104766A (zh) |
BR (1) | BR9908702A (zh) |
CA (1) | CA2322873A1 (zh) |
CU (1) | CU23047A3 (zh) |
DE (1) | DE69920670T2 (zh) |
EA (1) | EA200000826A1 (zh) |
EE (1) | EE200000519A (zh) |
ES (1) | ES2239839T3 (zh) |
GE (1) | GEP20043179B (zh) |
HR (1) | HRP20000595A2 (zh) |
HU (1) | HUP0101467A3 (zh) |
ID (1) | ID26208A (zh) |
IL (1) | IL137654A0 (zh) |
IS (1) | IS5583A (zh) |
NO (1) | NO20004531L (zh) |
NZ (1) | NZ506721A (zh) |
OA (1) | OA11901A (zh) |
PL (1) | PL343380A1 (zh) |
PT (1) | PT1062201E (zh) |
SI (1) | SI1062201T1 (zh) |
SK (1) | SK13012000A3 (zh) |
TR (1) | TR200002605T2 (zh) |
UA (1) | UA67767C2 (zh) |
WO (1) | WO1999046240A2 (zh) |
YU (1) | YU52200A (zh) |
ZA (1) | ZA991894B (zh) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2001247745B2 (en) | 2000-03-24 | 2006-08-31 | Pharmacia Corporation | Amidino compounds useful as nitric oxide synthase inhibitors |
US6956131B2 (en) | 2000-04-13 | 2005-10-18 | Pharmacia Corporation | 2-amino-3, 4 heptenoic compounds useful as nitric oxide synthase inhibitors |
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 |
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 |
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 |
AR031129A1 (es) * | 2000-09-15 | 2003-09-10 | Pharmacia Corp | Derivados de los acidos 2-amino-2-alquil-4-hexenoico y -hexinoico utiles como inhibidores de oxido nitrico sintetasa |
AR035585A1 (es) * | 2000-09-15 | 2004-06-16 | Pharmacia Corp | Derivados del acido 2-amino-2-alquil-4-heptenoico, composicion farmaceutica y su uso en la fabricacion de medicamentos |
AR031608A1 (es) * | 2000-09-15 | 2003-09-24 | Pharmacia Corp | Derivados de los acidos 2-amino-2-alquil-3-hexenoico y -hexinoico utiles como inhibidores de oxido nitrico sintetasa |
AR031609A1 (es) * | 2000-09-15 | 2003-09-24 | Pharmacia Corp | Derivados de acido 2-amino-2-alquil-3 heptenoico y heptinoico utiles como inhibidores de oxido nitrico sintetasa |
GB0031179D0 (en) | 2000-12-21 | 2001-01-31 | Glaxo Group Ltd | Nitric oxide synthase inhibitors |
US6613280B2 (en) * | 2001-03-20 | 2003-09-02 | Therox, Inc. | Disposable cartridge for producing gas-enriched fluids |
US6582387B2 (en) * | 2001-03-20 | 2003-06-24 | Therox, Inc. | System for enriching a bodily fluid with a gas |
US7012098B2 (en) | 2001-03-23 | 2006-03-14 | Pharmacia Corporation | Inhibitors of inducible nitric oxide synthase for chemoprevention and treatment of cancers |
EP1505972A2 (en) * | 2002-05-16 | 2005-02-16 | Pharmacia Corporation | A selective inos inhibitor and a pde inhibitor in combination for the treatment of respiratory diseases |
MX2007007590A (es) | 2004-12-22 | 2007-12-10 | Ambrx Inc | Composiciones que contienen, metodos que involucran y usos de aminoacidos no naturales y polipeptidos. |
JP5384933B2 (ja) * | 2005-03-14 | 2014-01-08 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | オピオイド調節物質の製造方法 |
CN101400646A (zh) * | 2005-11-08 | 2009-04-01 | Ambrx公司 | 用于修饰非天然氨基酸和非天然氨基酸多肽的促进剂 |
CN105384807A (zh) * | 2005-12-14 | 2016-03-09 | Ambrx公司 | 含有非天然氨基酸和多肽的组合物、涉及非天然氨基酸和多肽的方法以及非天然氨基酸和多肽的用途 |
KR101103720B1 (ko) * | 2011-06-02 | 2012-01-11 | 한국건설기술연구원 | 자연환기에 의한 중공층의 온도제어가 가능한 일체형 다중유리 복합창짝 |
AU2014317884B2 (en) | 2013-09-09 | 2017-09-07 | Canimguide Therapeutics Ab | Immune system modulators |
ES2853582T3 (es) | 2015-03-06 | 2021-09-16 | Canimguide Therapeutics Ab | Moduladores del sistema inmune y composiciones |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9127376D0 (en) * | 1991-12-24 | 1992-02-19 | Wellcome Found | Amidino derivatives |
GB9312761D0 (en) * | 1993-06-21 | 1993-08-04 | Wellcome Found | Amino acid derivatives |
US5889056A (en) * | 1994-06-15 | 1999-03-30 | Glaxo Wellsome Inc. | Enzyme inhibitors |
GB9425701D0 (en) | 1994-12-20 | 1995-02-22 | Wellcome Found | Enzyme inhibitors |
US5981511A (en) * | 1996-03-06 | 1999-11-09 | G.D. Searle & Co. | Hydroxyamidino derivatives useful as nitric oxide synthase inhibitors |
US5945408A (en) | 1996-03-06 | 1999-08-31 | G.D. Searle & Co. | Hydroxyanidino derivatives useful as nitric oxide synthase inhibitors |
-
1999
- 1999-03-04 PT PT99908324T patent/PT1062201E/pt unknown
- 1999-03-04 TR TR2000/02605T patent/TR200002605T2/xx unknown
- 1999-03-04 PL PL99343380A patent/PL343380A1/xx unknown
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