OA11901A - 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
- OA11901A OA11901A OA1200000239A OA1200000239A OA11901A OA 11901 A OA11901 A OA 11901A OA 1200000239 A OA1200000239 A OA 1200000239A OA 1200000239 A OA1200000239 A OA 1200000239A OA 11901 A OA11901 A OA 11901A
- Authority
- OA
- OAPI
- Prior art keywords
- alkyl
- dihydrochloride
- alkynyl
- group
- amino
- Prior art date
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- -1 amidino amino Chemical class 0.000 title claims abstract description 73
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 title description 3
- CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 74
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 57
- 150000002367 halogens Chemical class 0.000 claims abstract description 57
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 56
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 54
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 35
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 27
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 19
- 125000003118 aryl group Chemical group 0.000 claims abstract description 16
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 16
- 125000005026 carboxyaryl group Chemical group 0.000 claims abstract description 13
- 125000005309 thioalkoxy group Chemical group 0.000 claims abstract description 13
- 125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 11
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 10
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 8
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 8
- 125000004419 alkynylene group Chemical group 0.000 claims abstract description 8
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims abstract description 7
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims abstract description 6
- 125000004385 trihaloalkyl group Chemical group 0.000 claims abstract description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 94
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 63
- 150000001875 compounds Chemical class 0.000 claims description 54
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 23
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 16
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 14
- 150000002431 hydrogen Chemical group 0.000 claims description 12
- 150000003573 thiols Chemical class 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 5
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical compound NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004982 dihaloalkyl group Chemical group 0.000 claims description 4
- 230000005764 inhibitory process Effects 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
- 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
- FSKNKXHSHHUMES-UHFFFAOYSA-N 2-[3-aminopropyl-(2-fluoroethanimidoyl)amino]-4-sulfanylbutanoic acid dihydrochloride Chemical compound Cl.Cl.FCC(=N)N(C(CCS)C(=O)O)CCCN FSKNKXHSHHUMES-UHFFFAOYSA-N 0.000 claims description 2
- BWFRGRNMMMKRQZ-UHFFFAOYSA-N 2-amino-6-[(1-amino-2-fluoroethylidene)amino]hex-4-ynoic acid;hydrochloride Chemical compound Cl.OC(=O)C(N)CC#CCNC(=N)CF BWFRGRNMMMKRQZ-UHFFFAOYSA-N 0.000 claims description 2
- RQBNXPJPWKUTOG-UHFFFAOYSA-N Azabon Chemical compound C1=CC(N)=CC=C1S(=O)(=O)N1CC(CC2)CCC2C1 RQBNXPJPWKUTOG-UHFFFAOYSA-N 0.000 claims description 2
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 2
- 101150020251 NR13 gene Proteins 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 claims 1
- 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 1
- 239000003112 inhibitor Substances 0.000 abstract description 11
- 150000003839 salts Chemical class 0.000 abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 206010020772 Hypertension Diseases 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 7
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 4
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 abstract 2
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 abstract 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 2
- 102220568291 Histone PARylation factor 1_R12H_mutation Human genes 0.000 abstract 1
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- 150000003862 amino acid derivatives Chemical class 0.000 abstract 1
- 230000000202 analgesic effect Effects 0.000 abstract 1
- 230000001093 anti-cancer Effects 0.000 abstract 1
- 230000003178 anti-diabetic effect Effects 0.000 abstract 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract 1
- 239000003472 antidiabetic agent Substances 0.000 abstract 1
- 230000003182 bronchodilatating effect Effects 0.000 abstract 1
- 230000002526 effect on cardiovascular system Effects 0.000 abstract 1
- 230000002496 gastric effect Effects 0.000 abstract 1
- 230000001631 hypertensive effect Effects 0.000 abstract 1
- 230000002519 immonomodulatory effect Effects 0.000 abstract 1
- 230000010534 mechanism of action Effects 0.000 abstract 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- 239000000243 solution Substances 0.000 description 27
- 239000003921 oil Substances 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 125000004432 carbon atom Chemical group C* 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
- 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
- 238000009472 formulation Methods 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
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- 238000004587 chromatography analysis Methods 0.000 description 9
- 150000004699 copper complex Chemical class 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 7
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 7
- 229960003753 nitric oxide Drugs 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 206010040070 Septic Shock Diseases 0.000 description 6
- 150000001409 amidines Chemical group 0.000 description 6
- 239000003242 anti bacterial agent Substances 0.000 description 6
- 229940088710 antibiotic agent Drugs 0.000 description 6
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- MULVVEXEENBHMQ-UHFFFAOYSA-N ethyl 2-fluoroethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)CF MULVVEXEENBHMQ-UHFFFAOYSA-N 0.000 description 5
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- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 4
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 238000010907 mechanical stirring Methods 0.000 description 1
- OGBINJLTBZWRRB-UHFFFAOYSA-N methyl 2,2,2-trichloroethanimidate Chemical compound COC(=N)C(Cl)(Cl)Cl OGBINJLTBZWRRB-UHFFFAOYSA-N 0.000 description 1
- SMWNFFKPVLVOQQ-UHFFFAOYSA-N methyl 2-acetamidoprop-2-enoate Chemical compound COC(=O)C(=C)NC(C)=O SMWNFFKPVLVOQQ-UHFFFAOYSA-N 0.000 description 1
- DYMKGQRODFWYQX-UHFFFAOYSA-N methyl 2-aminoprop-2-enoate Chemical compound COC(=O)C(N)=C DYMKGQRODFWYQX-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
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- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
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- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 125000002347 octyl 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])[H] 0.000 description 1
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- 230000008052 pain pathway Effects 0.000 description 1
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- 235000010603 pastilles Nutrition 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000005470 propylenyl group Chemical group 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 201000004700 rosacea Diseases 0.000 description 1
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 1
- 229960004617 sapropterin Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
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- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
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- 239000000126 substance Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
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- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- ZQZKMHODQLBJTD-UHFFFAOYSA-N tert-butyl 3-amino-3-sulfanylpropanoate Chemical compound CC(C)(C)OC(=O)CC(N)S ZQZKMHODQLBJTD-UHFFFAOYSA-N 0.000 description 1
- FVQYBAASQSUZOP-UHFFFAOYSA-N tert-butyl n-(4-chlorobut-2-ynyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC#CCCl FVQYBAASQSUZOP-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
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- 210000001519 tissue Anatomy 0.000 description 1
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- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- 238000010792 warming Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3828498A | 1998-03-11 | 1998-03-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA11901A true OA11901A (en) | 2006-04-10 |
Family
ID=21899068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA1200000239A OA11901A (en) | 1998-03-11 | 1999-03-04 | Halogenated amidino amino acid derivatives useful as nitric oxide synthase inhibitors. |
Country Status (35)
| Country | Link |
|---|---|
| US (1) | US6344483B1 (et) |
| EP (2) | EP1062201B1 (et) |
| JP (1) | JP2002506056A (et) |
| KR (1) | KR20010034598A (et) |
| CN (1) | CN1171861C (et) |
| AP (1) | AP2000001900A0 (et) |
| AR (1) | AR018159A1 (et) |
| AT (1) | ATE277894T1 (et) |
| AU (1) | AU746235B2 (et) |
| BG (1) | BG104766A (et) |
| BR (1) | BR9908702A (et) |
| CA (1) | CA2322873A1 (et) |
| CU (1) | CU23047A3 (et) |
| DE (1) | DE69920670T2 (et) |
| EA (1) | EA200000826A1 (et) |
| EE (1) | EE200000519A (et) |
| ES (1) | ES2239839T3 (et) |
| GE (1) | GEP20043179B (et) |
| HR (1) | HRP20000595A2 (et) |
| HU (1) | HUP0101467A3 (et) |
| ID (1) | ID26208A (et) |
| IL (1) | IL137654A0 (et) |
| IS (1) | IS5583A (et) |
| NO (1) | NO20004531L (et) |
| NZ (1) | NZ506721A (et) |
| OA (1) | OA11901A (et) |
| PL (1) | PL343380A1 (et) |
| PT (1) | PT1062201E (et) |
| SI (1) | SI1062201T1 (et) |
| SK (1) | SK13012000A3 (et) |
| TR (1) | TR200002605T2 (et) |
| UA (1) | UA67767C2 (et) |
| WO (1) | WO1999046240A2 (et) |
| YU (1) | YU52200A (et) |
| ZA (1) | ZA991894B (et) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1265860E (pt) | 2000-03-24 | 2005-10-31 | Pharmacia Corp | Compostos amidino uteis como inibidores de sintase de oxido nitrico |
| 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 |
| US6956131B2 (en) | 2000-04-13 | 2005-10-18 | Pharmacia Corporation | 2-amino-3, 4 heptenoic compounds useful as nitric oxide synthase inhibitors |
| US6545170B2 (en) | 2000-04-13 | 2003-04-08 | Pharmacia Corporation | 2-amino-5, 6 heptenoic acid derivatives 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 |
| US6787668B2 (en) | 2000-04-13 | 2004-09-07 | Pharmacia Corporation | 2-amino-4,5 heptenoic acid derivatives useful as nitric oxide synthase inhibitors |
| 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 |
| 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 |
| 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 |
| BR0310061A (pt) * | 2002-05-16 | 2005-03-01 | Pharmacia Corp | Métodos para o tratamento de doenças e condições respiratórias com um inibidor seletivo da inos e um inibidor da pde e suas composições |
| US7332571B2 (en) * | 2004-12-22 | 2008-02-19 | Ambrx, Inc. | Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides |
| US20060211861A1 (en) * | 2005-03-14 | 2006-09-21 | Chaozhong Cai | Process for the preparation of opioid modulators |
| SI1954710T1 (sl) | 2005-11-08 | 2011-08-31 | Ambrx Inc | Pospeĺ evala za modifikacijo nenaravnih aminokislin in nenaravnih peptidov aminokislin |
| JP2009519942A (ja) * | 2005-12-14 | 2009-05-21 | アンブルックス，インコーポレイテッド | 非天然アミノ酸およびポリペプチドを含んでいる組成物、それらに関する方法、ならびに、それらの使用 |
| KR101103720B1 (ko) * | 2011-06-02 | 2012-01-11 | 한국건설기술연구원 | 자연환기에 의한 중공층의 온도제어가 가능한 일체형 다중유리 복합창짝 |
| CN111732652A (zh) | 2013-09-09 | 2020-10-02 | 卡尼姆盖德治疗学公司 | 免疫系统调节器 |
| EP3265117B1 (en) | 2015-03-06 | 2020-11-11 | CanImGuide Therapeutics AB | Immune system modulators and compositions |
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 |
| ES2189322T3 (es) * | 1994-06-15 | 2003-07-01 | Wellcome Found | Intermediarios utiles en la preparacion de inhibidores de encimas. |
| GB9425701D0 (en) | 1994-12-20 | 1995-02-22 | Wellcome Found | Enzyme inhibitors |
| US5945408A (en) * | 1996-03-06 | 1999-08-31 | G.D. Searle & Co. | Hydroxyanidino derivatives useful as nitric oxide synthase inhibitors |
| US5981511A (en) * | 1996-03-06 | 1999-11-09 | G.D. Searle & Co. | Hydroxyamidino derivatives useful as nitric oxide synthase inhibitors |
-
1999
- 1999-03-04 US US09/402,953 patent/US6344483B1/en not_active Expired - Fee Related
- 1999-03-04 EP EP99908324A patent/EP1062201B1/en not_active Expired - Lifetime
- 1999-03-04 PT PT99908324T patent/PT1062201E/pt unknown
- 1999-03-04 JP JP2000535621A patent/JP2002506056A/ja active Pending
- 1999-03-04 DE DE69920670T patent/DE69920670T2/de not_active Expired - Fee Related
- 1999-03-04 TR TR2000/02605T patent/TR200002605T2/xx unknown
- 1999-03-04 GE GEAP19995542A patent/GEP20043179B/en unknown
- 1999-03-04 CA CA002322873A patent/CA2322873A1/en not_active Abandoned
- 1999-03-04 EE EEP200000519A patent/EE200000519A/et unknown
- 1999-03-04 OA OA1200000239A patent/OA11901A/en unknown
- 1999-03-04 CN CNB998037907A patent/CN1171861C/zh not_active Expired - Fee Related
- 1999-03-04 NZ NZ506721A patent/NZ506721A/en unknown
- 1999-03-04 IL IL13765499A patent/IL137654A0/xx unknown
- 1999-03-04 ID IDW20001739A patent/ID26208A/id unknown
- 1999-03-04 SK SK1301-2000A patent/SK13012000A3/sk unknown
- 1999-03-04 EA EA200000826A patent/EA200000826A1/ru unknown
- 1999-03-04 AT AT99908324T patent/ATE277894T1/de not_active IP Right Cessation
- 1999-03-04 WO PCT/US1999/003728 patent/WO1999046240A2/en not_active Ceased
- 1999-03-04 YU YU52200A patent/YU52200A/sh unknown
- 1999-03-04 PL PL99343380A patent/PL343380A1/xx unknown
- 1999-03-04 SI SI9930718T patent/SI1062201T1/xx unknown
- 1999-03-04 AU AU27786/99A patent/AU746235B2/en not_active Ceased
- 1999-03-04 ES ES99908324T patent/ES2239839T3/es not_active Expired - Lifetime
- 1999-03-04 HU HU0101467A patent/HUP0101467A3/hu unknown
- 1999-03-04 BR BR9908702-2A patent/BR9908702A/pt not_active Application Discontinuation
- 1999-03-04 CU CU20000199A patent/CU23047A3/es unknown
- 1999-03-04 EP EP20040001236 patent/EP1415982A1/en not_active Withdrawn
- 1999-03-04 KR KR1020007010096A patent/KR20010034598A/ko not_active Ceased
- 1999-03-04 HR HR20000595A patent/HRP20000595A2/hr not_active Application Discontinuation
- 1999-03-04 AP APAP/P/2000/001900A patent/AP2000001900A0/en unknown
- 1999-03-09 ZA ZA9901894A patent/ZA991894B/xx unknown
- 1999-03-11 AR ARP990101062A patent/AR018159A1/es unknown
- 1999-04-03 UA UA2000095233A patent/UA67767C2/uk unknown
-
2000
- 2000-08-04 IS IS5583A patent/IS5583A/is unknown
- 2000-09-11 NO NO20004531A patent/NO20004531L/no not_active Application Discontinuation
- 2000-09-14 BG BG104766A patent/BG104766A/bg unknown
Also Published As
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