NO310618B1 - Kondenserte piperidinforbindelser, fremstilling og anvendelse derav, samt preparater omfattende slike forbindelser - Google Patents
Kondenserte piperidinforbindelser, fremstilling og anvendelse derav, samt preparater omfattende slike forbindelser Download PDFInfo
- Publication number
- NO310618B1 NO310618B1 NO19981658A NO981658A NO310618B1 NO 310618 B1 NO310618 B1 NO 310618B1 NO 19981658 A NO19981658 A NO 19981658A NO 981658 A NO981658 A NO 981658A NO 310618 B1 NO310618 B1 NO 310618B1
- Authority
- NO
- Norway
- Prior art keywords
- azabicyclo
- imino
- heptane
- trans
- methyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 80
- 238000002360 preparation method Methods 0.000 title claims description 46
- 150000003053 piperidines Chemical class 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 239000004480 active ingredient Substances 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 28
- -1 piperidine compound Chemical class 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 17
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 12
- 231100000252 nontoxic Toxicity 0.000 claims description 12
- 230000003000 nontoxic effect Effects 0.000 claims description 12
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 10
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 208000035475 disorder Diseases 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 230000035939 shock Effects 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 206010061876 Obstruction Diseases 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 235000019270 ammonium chloride Nutrition 0.000 claims description 6
- 230000006378 damage Effects 0.000 claims description 6
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- 208000001953 Hypotension Diseases 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 208000026062 Tissue disease Diseases 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 230000002490 cerebral effect Effects 0.000 claims description 4
- 230000004720 fertilization Effects 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 230000036543 hypotension Effects 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- 230000000302 ischemic effect Effects 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- 125000004011 3 membered carbocyclic group Chemical group 0.000 claims description 3
- 125000001845 4 membered carbocyclic group Chemical group 0.000 claims description 3
- 208000030507 AIDS Diseases 0.000 claims description 3
- 206010000830 Acute leukaemia Diseases 0.000 claims description 3
- 208000007848 Alcoholism Diseases 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 208000002177 Cataract Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 206010053138 Congenital aplastic anaemia Diseases 0.000 claims description 3
- 208000000059 Dyspnea Diseases 0.000 claims description 3
- 206010013975 Dyspnoeas Diseases 0.000 claims description 3
- 206010014561 Emphysema Diseases 0.000 claims description 3
- 201000004939 Fanconi anemia Diseases 0.000 claims description 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 208000004554 Leishmaniasis Diseases 0.000 claims description 3
- 208000034486 Multi-organ failure Diseases 0.000 claims description 3
- 208000010718 Multiple Organ Failure Diseases 0.000 claims description 3
- 208000009525 Myocarditis Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 3
- 206010033645 Pancreatitis Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 3
- 208000031845 Pernicious anaemia Diseases 0.000 claims description 3
- 208000025747 Rheumatic disease Diseases 0.000 claims description 3
- 206010040047 Sepsis Diseases 0.000 claims description 3
- 206010042496 Sunburn Diseases 0.000 claims description 3
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 206010047631 Vitamin E deficiency Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 201000010275 acute porphyria Diseases 0.000 claims description 3
- 230000032683 aging Effects 0.000 claims description 3
- 201000007930 alcohol dependence Diseases 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 210000004204 blood vessel Anatomy 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 208000024207 chronic leukemia Diseases 0.000 claims description 3
- 230000006806 disease prevention Effects 0.000 claims description 3
- 208000033552 hepatic porphyria Diseases 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 206010022000 influenza Diseases 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- 201000004792 malaria Diseases 0.000 claims description 3
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 201000006938 muscular dystrophy Diseases 0.000 claims description 3
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 230000005855 radiation Effects 0.000 claims description 3
- 230000010410 reperfusion Effects 0.000 claims description 3
- 230000000552 rheumatic effect Effects 0.000 claims description 3
- 208000007056 sickle cell anemia Diseases 0.000 claims description 3
- 125000003003 spiro group Chemical group 0.000 claims description 3
- 230000035882 stress Effects 0.000 claims description 3
- 201000008827 tuberculosis Diseases 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 210000004088 microvessel Anatomy 0.000 claims description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 208000013223 septicemia Diseases 0.000 claims description 2
- NWTQDKWILGCZMF-UHFFFAOYSA-N 6-azaspiro[2.5]oct-6-en-7-amine Chemical group C1C(N)=NCCC11CC1 NWTQDKWILGCZMF-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract description 14
- 239000003112 inhibitor Substances 0.000 abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 115
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 94
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 60
- 238000004809 thin layer chromatography Methods 0.000 description 49
- 239000000243 solution Substances 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 230000000704 physical effect Effects 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 239000012300 argon atmosphere Substances 0.000 description 10
- 150000002431 hydrogen Chemical class 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 125000000623 heterocyclic group Chemical group 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000003701 inert diluent Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 4
- 125000003282 alkyl amino group Chemical group 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 125000004103 aminoalkyl group Chemical group 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000004663 dialkyl amino group Chemical group 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
- 229930064664 L-arginine Natural products 0.000 description 3
- 235000014852 L-arginine Nutrition 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 229940123921 Nitric oxide synthase inhibitor Drugs 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 235000009697 arginine Nutrition 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 3
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 108010044467 Isoenzymes Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 2
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 2
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 2
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 125000002877 alkyl aryl group Chemical group 0.000 description 2
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 2
- 125000005001 aminoaryl group Chemical group 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 125000001769 aryl amino group Chemical group 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229960002173 citrulline Drugs 0.000 description 2
- BQVVSSAWECGTRN-UHFFFAOYSA-L copper;dithiocyanate Chemical compound [Cu+2].[S-]C#N.[S-]C#N BQVVSSAWECGTRN-UHFFFAOYSA-L 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 2
- QFXKXRXFBRLLPQ-UHFFFAOYSA-N diphenyleneiodonium Chemical compound C1=CC=C2[I+]C3=CC=CC=C3C2=C1 QFXKXRXFBRLLPQ-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- ZOQWONKTSYEVDD-UHFFFAOYSA-N dithiophen-2-yliodanium Chemical compound C=1C=CSC=1[I+]C1=CC=CS1 ZOQWONKTSYEVDD-UHFFFAOYSA-N 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- VWWQXMAJTJZDQX-UYBVJOGSSA-N flavin adenine dinucleotide Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1CO[P@](O)(=O)O[P@@](O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 VWWQXMAJTJZDQX-UYBVJOGSSA-N 0.000 description 2
- 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 2
- 239000011714 flavin adenine dinucleotide Substances 0.000 description 2
- 229940093632 flavin-adenine dinucleotide Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000011698 potassium fluoride Substances 0.000 description 2
- 235000003270 potassium fluoride Nutrition 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000002040 relaxant effect Effects 0.000 description 2
- 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 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- YLGRTLMDMVAFNI-UHFFFAOYSA-N tributyl(prop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC=C YLGRTLMDMVAFNI-UHFFFAOYSA-N 0.000 description 2
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 2
- NFHRNKANAAGQOH-UHFFFAOYSA-N triphenylstannane Chemical compound C1=CC=CC=C1[SnH](C=1C=CC=CC=1)C1=CC=CC=C1 NFHRNKANAAGQOH-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- YGVMJVSXFJRHGQ-WCCKRBBISA-N (2S)-2-amino-5-[[amino(hydrazinyl)methylidene]amino]pentanoic acid hydrochloride Chemical compound Cl.NN\C(N)=N\CCC[C@H](N)C(O)=O YGVMJVSXFJRHGQ-WCCKRBBISA-N 0.000 description 1
- QYGXVJHXZUSLQC-JEDNCBNOSA-N (2s)-2-amino-5-[(n'-methylcarbamimidoyl)amino]pentanoic acid;hydron;chloride Chemical compound Cl.CN=C(N)NCCC[C@H](N)C(O)=O QYGXVJHXZUSLQC-JEDNCBNOSA-N 0.000 description 1
- ZYECOAILUNWEAL-NUDFZHEQSA-N (4z)-4-[[2-methoxy-5-(phenylcarbamoyl)phenyl]hydrazinylidene]-n-(3-nitrophenyl)-3-oxonaphthalene-2-carboxamide Chemical compound COC1=CC=C(C(=O)NC=2C=CC=CC=2)C=C1N\N=C(C1=CC=CC=C1C=1)/C(=O)C=1C(=O)NC1=CC=CC([N+]([O-])=O)=C1 ZYECOAILUNWEAL-NUDFZHEQSA-N 0.000 description 1
- BWEFNFZSJFYSAP-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-4-methyl-3,4-dihydropyridin-2-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)CC(C)C=C1 BWEFNFZSJFYSAP-UHFFFAOYSA-N 0.000 description 1
- GXBVRZREPIFJJQ-UHFFFAOYSA-N 2-[1-(2-aminoethyl)cyclopropyl]acetonitrile Chemical compound NCCC1(CC#N)CC1 GXBVRZREPIFJJQ-UHFFFAOYSA-N 0.000 description 1
- UZFFTUDTQFIMFY-UHFFFAOYSA-N 2-[1-(cyanomethyl)cyclopropyl]acetonitrile Chemical compound N#CCC1(CC#N)CC1 UZFFTUDTQFIMFY-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- VVQSYDQNTWBJNS-UHFFFAOYSA-N 4-methyl-2,5-dihydro-1h-pyridin-6-one Chemical compound CC1=CCNC(=O)C1 VVQSYDQNTWBJNS-UHFFFAOYSA-N 0.000 description 1
- IABPPWDLZYMCFD-UHFFFAOYSA-N 7-ethoxy-6-azaspiro[2.5]oct-6-ene;hydrochloride Chemical compound Cl.C1C(OCC)=NCCC11CC1 IABPPWDLZYMCFD-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 102000004631 Calcineurin Human genes 0.000 description 1
- 108010042955 Calcineurin Proteins 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- BALPWQOALKPFFI-UHFFFAOYSA-N Cl.C1CNC(=N)CC11CC1 Chemical compound Cl.C1CNC(=N)CC11CC1 BALPWQOALKPFFI-UHFFFAOYSA-N 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102220480121 H/ACA ribonucleoprotein complex subunit DKC1_R10A_mutation Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- UYZFAUAYFLEHRC-LURJTMIESA-N L-NIO Chemical compound CC(N)=NCCC[C@H](N)C(O)=O UYZFAUAYFLEHRC-LURJTMIESA-N 0.000 description 1
- MRAUNPAHJZDYCK-BYPYZUCNSA-N L-nitroarginine Chemical compound OC(=O)[C@@H](N)CCCNC(=N)N[N+]([O-])=O MRAUNPAHJZDYCK-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- UYZFAUAYFLEHRC-UHFFFAOYSA-N NG-iminoethyl-L-ornithine Natural products CC(N)=NCCCC(N)C(O)=O UYZFAUAYFLEHRC-UHFFFAOYSA-N 0.000 description 1
- NTNWOCRCBQPEKQ-UHFFFAOYSA-N NG-mono-methyl-L-arginine Natural products CN=C(N)NCCCC(N)C(O)=O NTNWOCRCBQPEKQ-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 1
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 1
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- UADBHFTWQBWLOF-UHFFFAOYSA-N [Li].CCCC[Cu]CCCC Chemical compound [Li].CCCC[Cu]CCCC UADBHFTWQBWLOF-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000001943 adrenal medulla Anatomy 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
- 125000006598 aminocarbonylamino group Chemical group 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- RXGDWZCMJCMFNW-UHFFFAOYSA-N bicyclo[3.2.0]heptan-3-one Chemical compound C1C(=O)CC2CCC21 RXGDWZCMJCMFNW-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229950005228 bromoform Drugs 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- CHRHZFQUDFAQEQ-UHFFFAOYSA-L calcium;2-hydroxyacetate Chemical compound [Ca+2].OCC([O-])=O.OCC([O-])=O CHRHZFQUDFAQEQ-UHFFFAOYSA-L 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- GFHNAMRJFCEERV-UHFFFAOYSA-L cobalt chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Co+2] GFHNAMRJFCEERV-UHFFFAOYSA-L 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 208000023589 ischemic disease Diseases 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000005165 macula densa Anatomy 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 210000003584 mesangial cell Anatomy 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 210000004493 neutrocyte Anatomy 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- NIXKBAZVOQAHGC-UHFFFAOYSA-N phenylmethanesulfonic acid Chemical compound OS(=O)(=O)CC1=CC=CC=C1 NIXKBAZVOQAHGC-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229960004617 sapropterin Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- LHHPEAQVCCPLBC-UHFFFAOYSA-N tributyltin;hydrate Chemical compound O.CCCC[Sn](CCCC)CCCC LHHPEAQVCCPLBC-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9183097 | 1997-04-10 | ||
JP27319697 | 1997-10-07 |
Publications (3)
Publication Number | Publication Date |
---|---|
NO981658D0 NO981658D0 (no) | 1998-04-08 |
NO981658L NO981658L (no) | 1998-10-12 |
NO310618B1 true NO310618B1 (no) | 2001-07-30 |
Family
ID=26433266
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19981658A NO310618B1 (no) | 1997-04-10 | 1998-04-08 | Kondenserte piperidinforbindelser, fremstilling og anvendelse derav, samt preparater omfattende slike forbindelser |
Country Status (14)
Country | Link |
---|---|
US (2) | US6110930A (de) |
EP (1) | EP0870763B1 (de) |
KR (1) | KR19980081287A (de) |
CN (1) | CN1202486A (de) |
AT (1) | ATE210647T1 (de) |
AU (1) | AU746048B2 (de) |
CA (1) | CA2234571A1 (de) |
DE (1) | DE69802858T2 (de) |
DK (1) | DK0870763T3 (de) |
ES (1) | ES2169886T3 (de) |
HU (1) | HUP9800865A3 (de) |
NO (1) | NO310618B1 (de) |
PT (1) | PT870763E (de) |
TW (1) | TW427979B (de) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2793248B1 (fr) * | 1999-05-03 | 2001-06-29 | Adir | Nouveaux derives de 2,3-methano-aminoacides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
KR20020008215A (ko) * | 1999-06-09 | 2002-01-29 | 우에노 도시오 | 진통제 |
FR2794647A1 (fr) | 1999-06-11 | 2000-12-15 | Centre Nat Rech Scient | Compositions pharmaceutique comprenant du no ou au moins un compose capable de liberer ou d'induire la formation de no dans les cellules |
MXPA01013261A (es) * | 1999-06-22 | 2002-08-12 | Ono Pharmaceutical Co | Proceso para la preparacion de compuestos intermediarios de farmaceuticos. |
FR2803298A1 (fr) * | 1999-12-30 | 2001-07-06 | Adir | Nouvelles urees lineaires ou cycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
KR20020073544A (ko) * | 2000-02-10 | 2002-09-26 | 오노 야꾸힝 고교 가부시키가이샤 | 쉐그렌 증후군의 치료제 |
WO2002036572A1 (fr) * | 2000-10-30 | 2002-05-10 | Ono Pharmaceutical Co., Ltd. | Remedes contre les maladies inflammatoires extra-oculaires |
EP1426060A4 (de) * | 2001-09-10 | 2004-12-01 | Ono Pharmaceutical Co | Mittel zur behandlung von allergischen erkrankungen |
JP2006096665A (ja) * | 2002-10-29 | 2006-04-13 | Ono Pharmaceut Co Ltd | 脊柱管狭窄症治療剤 |
EP1626961B1 (de) * | 2003-05-17 | 2011-11-02 | Korea Research Institute of Bioscience and Biotechnology | Neue heterozyklische 2-oxo-verbindungen und pharmazeutische zusammensetzungen, die diese enthalten |
US20050234026A1 (en) * | 2003-11-10 | 2005-10-20 | Weinberg Joe B | Method and agent for inducing apoptosis/cell death in leukemia cells |
US20090186929A1 (en) * | 2003-11-10 | 2009-07-23 | U.S. Department Of Veterans Affairs | Method and agent for inducing apoptosis/cell death in leukemia cells |
US7364437B2 (en) * | 2005-08-04 | 2008-04-29 | Seagate Technology Llc | Electronic device housing |
EP2112955A2 (de) | 2007-02-19 | 2009-11-04 | DSM IP Assets B.V. | Neuartige pt-metallgruppenkatalysatoren und herstellungsverfahren dafür |
WO2018035046A1 (en) | 2016-08-15 | 2018-02-22 | President And Fellows Of Harvard College | Treating infections using idsd from proteus mirabilis |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69416848T2 (de) * | 1993-10-21 | 1999-07-08 | G.D. Searle & Co., Chicago, Ill. | Amidino-derivate als no-synthetase inhibitoren |
WO1996014842A1 (en) * | 1994-11-15 | 1996-05-23 | Merck & Co., Inc. | Substituted heterocycles as inhibitors of nitric oxide synthase |
US5629322A (en) * | 1994-11-15 | 1997-05-13 | Merck & Co., Inc. | Cyclic amidine analogs as inhibitors of nitric oxide synthase |
NZ307950A (en) * | 1995-05-10 | 1999-06-29 | Searle & Co | Cyclic amidines derivatives and medicaments thereof |
-
1998
- 1998-04-08 NO NO19981658A patent/NO310618B1/no not_active IP Right Cessation
- 1998-04-08 US US09/056,867 patent/US6110930A/en not_active Expired - Fee Related
- 1998-04-09 PT PT98106569T patent/PT870763E/pt unknown
- 1998-04-09 EP EP98106569A patent/EP0870763B1/de not_active Expired - Lifetime
- 1998-04-09 CA CA002234571A patent/CA2234571A1/en not_active Abandoned
- 1998-04-09 DE DE69802858T patent/DE69802858T2/de not_active Expired - Fee Related
- 1998-04-09 DK DK98106569T patent/DK0870763T3/da active
- 1998-04-09 TW TW087105329A patent/TW427979B/zh active
- 1998-04-09 CN CN98108834A patent/CN1202486A/zh active Pending
- 1998-04-09 AU AU60777/98A patent/AU746048B2/en not_active Ceased
- 1998-04-09 AT AT98106569T patent/ATE210647T1/de not_active IP Right Cessation
- 1998-04-09 ES ES98106569T patent/ES2169886T3/es not_active Expired - Lifetime
- 1998-04-10 HU HU9800865A patent/HUP9800865A3/hu unknown
- 1998-04-10 KR KR1019980012758A patent/KR19980081287A/ko not_active Application Discontinuation
-
2000
- 2000-03-13 US US09/524,255 patent/US6228866B1/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CA2234571A1 (en) | 1998-10-10 |
NO981658L (no) | 1998-10-12 |
KR19980081287A (ko) | 1998-11-25 |
HUP9800865A3 (en) | 1999-03-01 |
ATE210647T1 (de) | 2001-12-15 |
HUP9800865A2 (hu) | 1999-01-28 |
DE69802858D1 (de) | 2002-01-24 |
HU9800865D0 (en) | 1998-05-28 |
DK0870763T3 (da) | 2002-03-11 |
AU746048B2 (en) | 2002-04-11 |
US6228866B1 (en) | 2001-05-08 |
NO981658D0 (no) | 1998-04-08 |
ES2169886T3 (es) | 2002-07-16 |
EP0870763A1 (de) | 1998-10-14 |
US6110930A (en) | 2000-08-29 |
PT870763E (pt) | 2002-06-28 |
EP0870763B1 (de) | 2001-12-12 |
AU6077798A (en) | 1998-10-15 |
DE69802858T2 (de) | 2002-08-08 |
CN1202486A (zh) | 1998-12-23 |
TW427979B (en) | 2001-04-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO310618B1 (no) | Kondenserte piperidinforbindelser, fremstilling og anvendelse derav, samt preparater omfattende slike forbindelser | |
EP4282486A2 (de) | Komplementfaktor-b-inhibitor und pharmazeutische zusammensetzung davon, herstellungsverfahren dafür und verwendung davon | |
US6376536B1 (en) | Quaternary ammonium salts and their use | |
US20100113485A1 (en) | Piperidinylamino-thieno[2,3-D] Pyrimidine Compounds | |
JP3938936B2 (ja) | ラディシコール誘導体 | |
DE69219807T2 (de) | Thienopyridinderivate und diese enthaltende pharmazeutische Zubereitungen | |
US20210179632A1 (en) | Thienopiperidine derivative and use thereof | |
US20140243335A1 (en) | Substituted hydoxamic acids and uses thereof | |
CN111971287A (zh) | 作为trk激酶抑制剂的大环化合物 | |
JPH09132529A (ja) | 一酸化窒素合成酵素阻害剤 | |
EP4017591A1 (de) | Antimalaria-hexahydropyrimidinanaloga | |
AU2003271478A1 (en) | Substituted gamma-phenyl-delta-lactams and uses related thereto | |
EP0361831B1 (de) | Virushemmende Nukleosidmischung | |
SK5942002A3 (en) | Isoxazole derivatives to be used as phosphodiesterase vii inhibitors, use thereof and pharmaceutical composition comprising the same | |
US6369110B1 (en) | Substituted guanidine derivatives and process for producing the same | |
JPH0841008A (ja) | 一酸化窒素合成酵素阻害剤 | |
JP3060214B2 (ja) | 縮合ピペリジン化合物、その製造方法およびその化合物を有効成分とする薬剤 | |
MXPA98002756A (en) | A compound of piperidine condens | |
EP2716639A1 (de) | Inhibitoren der Virenreplikation, Verfahren zu deren Herstellung und deren therapeutische Verwendung | |
JPH09208562A (ja) | 一酸化窒素合成酵素阻害剤 | |
CN117343064B (zh) | 一种具有抗病毒作用的嘧啶衍生物的制备与应用 | |
US20070037867A1 (en) | Antihepatitis c virus agent and anti-hiv agent | |
CN114539142A (zh) | 吡啶酮类化合物,其药物组合物、制备方法和应用 | |
JPS6036487A (ja) | スピロスクシンイミド誘導体 | |
JPH101470A (ja) | 一酸化窒素合成酵素阻害剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |
Free format text: LAPSED IN OCTOBER 2003 |