SK287101B6 - Amidoxímové deriváty propénkarboxylovej kyseliny, spôsob ich prípravy a farmaceutické prípravky s ich obsahom - Google Patents

Info

Publication number

SK287101B6

SK287101B6 SK1350-2002A SK13502002A SK287101B6 SK 287101 B6 SK287101 B6 SK 287101B6 SK 13502002 A SK13502002 A SK 13502002A SK 287101 B6 SK287101 B6 SK 287101B6

Authority

SK

Slovakia

Prior art keywords

formula

compound

derivative

group

pharmaceutically acceptable

Prior art date

2000-03-20

Links

• Espacenet
• Global Dossier
• Discuss

• -1 Propenecarboxylic acid amidoxime derivatives Chemical class 0.000 title claims description 125
• 238000000034 method Methods 0.000 title claims description 72
• 238000002360 preparation method Methods 0.000 title claims description 34
• 230000008569 process Effects 0.000 title claims description 25
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 17
• 150000001875 compounds Chemical class 0.000 claims abstract description 197
• 239000002253 acid Substances 0.000 claims abstract description 72
• 150000003839 salts Chemical class 0.000 claims abstract description 55
• 238000011282 treatment Methods 0.000 claims abstract description 45
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
• 201000010099 disease Diseases 0.000 claims abstract description 30
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims abstract description 29
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims abstract description 28
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 26
• 150000001204 N-oxides Chemical class 0.000 claims abstract description 22
• 230000003287 optical effect Effects 0.000 claims abstract description 21
• 239000001301 oxygen Substances 0.000 claims abstract description 16
• LDHQCZJRKDOVOX-UHFFFAOYSA-N 2-butenoic acid Chemical compound CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 claims abstract description 15
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
• 230000004770 neurodegeneration Effects 0.000 claims abstract description 12
• 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 12
• 230000005764 inhibitory process Effects 0.000 claims abstract description 11
• 230000003612 virological effect Effects 0.000 claims abstract description 10
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 9
• 231100000331 toxic Toxicity 0.000 claims abstract description 9
• 230000002588 toxic effect Effects 0.000 claims abstract description 9
• 125000001424 substituent group Chemical group 0.000 claims description 40
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 33
• PCJFEVUKVKQSSL-UHFFFAOYSA-N 2h-1,2,4-oxadiazol-5-one Chemical compound O=C1N=CNO1 PCJFEVUKVKQSSL-UHFFFAOYSA-N 0.000 claims description 31
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
• 125000005843 halogen group Chemical group 0.000 claims description 27
• 229910052739 hydrogen Inorganic materials 0.000 claims description 27
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 25
• JKNSMBZZZFGYCB-UHFFFAOYSA-N 4,5-dihydrooxadiazole Chemical class C1CN=NO1 JKNSMBZZZFGYCB-UHFFFAOYSA-N 0.000 claims description 23
• 125000000217 alkyl group Chemical group 0.000 claims description 23
• 229910052717 sulfur Inorganic materials 0.000 claims description 21
• 125000003545 alkoxy group Chemical group 0.000 claims description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims description 19
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
• 125000004434 sulfur atom Chemical group 0.000 claims description 15
• 150000001412 amines Chemical class 0.000 claims description 14
• 239000001257 hydrogen Substances 0.000 claims description 14
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
• 239000004480 active ingredient Substances 0.000 claims description 13
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 11
• QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical class CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 10
• 239000011230 binding agent Substances 0.000 claims description 9
• 239000003795 chemical substances by application Substances 0.000 claims description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
• 229910001854 alkali hydroxide Inorganic materials 0.000 claims description 8
• 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 8
• 125000004414 alkyl thio group Chemical group 0.000 claims description 8
• 230000007812 deficiency Effects 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 150000004820 halides Chemical class 0.000 claims description 7
• 150000002431 hydrogen Chemical group 0.000 claims description 7
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 6
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims description 6
• BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 6
• 150000001350 alkyl halides Chemical group 0.000 claims description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
• 235000013985 cinnamic acid Nutrition 0.000 claims description 6
• 229930016911 cinnamic acid Natural products 0.000 claims description 6
• 230000002140 halogenating effect Effects 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims description 6
• 150000005063 oxadiazines Chemical class 0.000 claims description 6
• 150000002924 oxiranes Chemical class 0.000 claims description 6
• 229920006395 saturated elastomer Polymers 0.000 claims description 6
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
• 229940126062 Compound A Drugs 0.000 claims description 5
• NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 5
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 5
• 239000002585 base Substances 0.000 claims description 5
• 150000007524 organic acids Chemical class 0.000 claims description 5
• 239000007800 oxidant agent Substances 0.000 claims description 5
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 5
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
• 229940100198 alkylating agent Drugs 0.000 claims description 4
• 239000002168 alkylating agent Substances 0.000 claims description 4
• 150000001721 carbon Chemical group 0.000 claims description 4
• 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 4
• 239000000460 chlorine Substances 0.000 claims description 4
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
• IBHIUPPGDYCBSV-UHFFFAOYSA-N 1,2-dihydroimidazol-5-one Chemical compound O=C1NCN=C1 IBHIUPPGDYCBSV-UHFFFAOYSA-N 0.000 claims description 3
• 125000004423 acyloxy group Chemical group 0.000 claims description 3
• 150000001447 alkali salts Chemical class 0.000 claims description 3
• 239000007864 aqueous solution Substances 0.000 claims description 3
• 150000007522 mineralic acids Chemical class 0.000 claims description 3
• 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 125000002252 acyl group Chemical group 0.000 claims description 2
• 239000012050 conventional carrier Substances 0.000 claims description 2
• 150000001923 cyclic compounds Chemical class 0.000 claims description 2
• SFHYNDMGZXWXBU-LIMNOBDPSA-N 6-amino-2-[[(e)-(3-formylphenyl)methylideneamino]carbamoylamino]-1,3-dioxobenzo[de]isoquinoline-5,8-disulfonic acid Chemical compound O=C1C(C2=3)=CC(S(O)(=O)=O)=CC=3C(N)=C(S(O)(=O)=O)C=C2C(=O)N1NC(=O)N\N=C\C1=CC=CC(C=O)=C1 SFHYNDMGZXWXBU-LIMNOBDPSA-N 0.000 claims 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
• 230000001363 autoimmune Effects 0.000 abstract description 9
• 230000006735 deficit Effects 0.000 abstract description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
• 239000000243 solution Substances 0.000 description 52
• 230000000694 effects Effects 0.000 description 48
• 241001465754 Metazoa Species 0.000 description 46
• 210000004027 cell Anatomy 0.000 description 46
• 238000012360 testing method Methods 0.000 description 45
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 42
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 38
• 102000004190 Enzymes Human genes 0.000 description 35
• 108090000790 Enzymes Proteins 0.000 description 35
• 239000011541 reaction mixture Substances 0.000 description 35
• 238000006243 chemical reaction Methods 0.000 description 34
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 27
• 108090000623 proteins and genes Proteins 0.000 description 26
• 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 description 25
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 25
• 229960004316 cisplatin Drugs 0.000 description 25
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
• 206010021143 Hypoxia Diseases 0.000 description 23
• 206010022489 Insulin Resistance Diseases 0.000 description 22
• 239000003960 organic solvent Substances 0.000 description 22
• 239000002904 solvent Substances 0.000 description 22
• 238000005160 1H NMR spectroscopy Methods 0.000 description 21
• 230000002829 reductive effect Effects 0.000 description 21
• 102000004877 Insulin Human genes 0.000 description 19
• 108090001061 Insulin Proteins 0.000 description 19
• 229940125396 insulin Drugs 0.000 description 19
• MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 19
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
• 241000699670 Mus sp. Species 0.000 description 18
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 18
• 230000001953 sensory effect Effects 0.000 description 17
• 230000006378 damage Effects 0.000 description 16
• 230000007954 hypoxia Effects 0.000 description 16
• FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 16
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
• 230000001965 increasing effect Effects 0.000 description 15
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 15
• 239000000203 mixture Substances 0.000 description 15
• PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 14
• ZUZKDVHENRTHMH-UHFFFAOYSA-N 2h-1,2,4-oxadiazol-5-one;hydrochloride Chemical compound Cl.O=C1N=CNO1 ZUZKDVHENRTHMH-UHFFFAOYSA-N 0.000 description 14
• 238000002474 experimental method Methods 0.000 description 14
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
• 210000002966 serum Anatomy 0.000 description 14
• 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 13
• 239000008103 glucose Substances 0.000 description 13
• 210000005036 nerve Anatomy 0.000 description 13
• 210000001519 tissue Anatomy 0.000 description 13
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 13
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
• 102100034343 Integrase Human genes 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 230000000638 stimulation Effects 0.000 description 12
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 12
• 101000839464 Leishmania braziliensis Heat shock 70 kDa protein Proteins 0.000 description 11
• 241000283973 Oryctolagus cuniculus Species 0.000 description 11
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 11
• 210000004369 blood Anatomy 0.000 description 11
• 239000008280 blood Substances 0.000 description 11
• 230000002401 inhibitory effect Effects 0.000 description 11
• 208000028867 ischemia Diseases 0.000 description 11
• 229960005489 paracetamol Drugs 0.000 description 11
• 239000000047 product Substances 0.000 description 11
• 102000004169 proteins and genes Human genes 0.000 description 11
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• 208000018737 Parkinson disease Diseases 0.000 description 10
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 239000003814 drug Substances 0.000 description 10
• 230000007246 mechanism Effects 0.000 description 10
• 230000008018 melting Effects 0.000 description 10
• 238000002844 melting Methods 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• 108020004414 DNA Proteins 0.000 description 9
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 9
• 239000002158 endotoxin Substances 0.000 description 9
• 239000011976 maleic acid Substances 0.000 description 9
• 230000009467 reduction Effects 0.000 description 9
• 230000004044 response Effects 0.000 description 9
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 9
• 230000001988 toxicity Effects 0.000 description 9
• 231100000419 toxicity Toxicity 0.000 description 9
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 8
• 230000004913 activation Effects 0.000 description 8
• 210000004556 brain Anatomy 0.000 description 8
• 239000007795 chemical reaction product Substances 0.000 description 8
• ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 8
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
• 230000014509 gene expression Effects 0.000 description 8
• 229960001052 streptozocin Drugs 0.000 description 8
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
• 239000004215 Carbon black (E152) Substances 0.000 description 7
• 102000003855 L-lactate dehydrogenase Human genes 0.000 description 7
• 108700023483 L-lactate dehydrogenases Proteins 0.000 description 7
• GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 7
• ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 7
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 7
• 238000009835 boiling Methods 0.000 description 7
• 230000008602 contraction Effects 0.000 description 7
• 229930195733 hydrocarbon Natural products 0.000 description 7
• 150000002430 hydrocarbons Chemical class 0.000 description 7
• 210000002161 motor neuron Anatomy 0.000 description 7
• 230000010410 reperfusion Effects 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• 241000700159 Rattus Species 0.000 description 6
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 230000027455 binding Effects 0.000 description 6
• 239000000872 buffer Substances 0.000 description 6
• 230000030833 cell death Effects 0.000 description 6
• 239000013078 crystal Substances 0.000 description 6
• 230000034994 death Effects 0.000 description 6
• 206010012601 diabetes mellitus Diseases 0.000 description 6
• 230000006870 function Effects 0.000 description 6
• 125000003055 glycidyl group Chemical group C(C1CO1)* 0.000 description 6
• 230000000260 hypercholesteremic effect Effects 0.000 description 6
• 238000002347 injection Methods 0.000 description 6
• 239000007924 injection Substances 0.000 description 6
• 230000000302 ischemic effect Effects 0.000 description 6
• 229920006008 lipopolysaccharide Polymers 0.000 description 6
• NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 6
• 230000003647 oxidation Effects 0.000 description 6
• 238000007254 oxidation reaction Methods 0.000 description 6
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
• 208000033808 peripheral neuropathy Diseases 0.000 description 6
• 150000002978 peroxides Chemical class 0.000 description 6
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 208000024891 symptom Diseases 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• PQCAUHUKTBHUSA-UHFFFAOYSA-N 7-nitro-1h-indazole Chemical compound [O-][N+](=O)C1=CC=CC2=C1NN=C2 PQCAUHUKTBHUSA-UHFFFAOYSA-N 0.000 description 5
• ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 5
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 5
• 230000005778 DNA damage Effects 0.000 description 5
• 231100000277 DNA damage Toxicity 0.000 description 5
• 102000002812 Heat-Shock Proteins Human genes 0.000 description 5
• 108010004889 Heat-Shock Proteins Proteins 0.000 description 5
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 5
• 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 5
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 5
• 230000037396 body weight Effects 0.000 description 5
• 230000007423 decrease Effects 0.000 description 5
• 231100000673 dose–response relationship Toxicity 0.000 description 5
• 230000002440 hepatic effect Effects 0.000 description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
• 230000007830 nerve conduction Effects 0.000 description 5
• 239000002777 nucleoside Substances 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 230000036542 oxidative stress Effects 0.000 description 5
• 230000003950 pathogenic mechanism Effects 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 239000000758 substrate Substances 0.000 description 5
• 230000004083 survival effect Effects 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 4
• 201000006474 Brain Ischemia Diseases 0.000 description 4
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
• 206010008120 Cerebral ischaemia Diseases 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
• RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 4
• 102000053602 DNA Human genes 0.000 description 4
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
• 108060001084 Luciferase Proteins 0.000 description 4
• 241000699684 Meriones unguiculatus Species 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 4
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
• 206010033799 Paralysis Diseases 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 4
• 229960004373 acetylcholine Drugs 0.000 description 4
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
• 238000005576 amination reaction Methods 0.000 description 4
• 206010008118 cerebral infarction Diseases 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
• 229960003638 dopamine Drugs 0.000 description 4
• 210000003038 endothelium Anatomy 0.000 description 4
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
• 238000002649 immunization Methods 0.000 description 4
• 230000003053 immunization Effects 0.000 description 4
• 238000001802 infusion Methods 0.000 description 4
• 239000003112 inhibitor Substances 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• 210000004165 myocardium Anatomy 0.000 description 4
• 201000001119 neuropathy Diseases 0.000 description 4
• 230000007823 neuropathy Effects 0.000 description 4
• 210000000056 organ Anatomy 0.000 description 4
• LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 4
• 125000004076 pyridyl group Chemical group 0.000 description 4
• 230000011514 reflex Effects 0.000 description 4
• 230000001105 regulatory effect Effects 0.000 description 4
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 4
• 229960002555 zidovudine Drugs 0.000 description 4
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 3
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
• XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 206010019851 Hepatotoxicity Diseases 0.000 description 3
• 208000035150 Hypercholesterolemia Diseases 0.000 description 3
• 206010067125 Liver injury Diseases 0.000 description 3
• 241000699660 Mus musculus Species 0.000 description 3
• 239000012661 PARP inhibitor Substances 0.000 description 3
• 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 206010040070 Septic Shock Diseases 0.000 description 3
• OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 3
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
• 208000006906 Vascular Ring Diseases 0.000 description 3
• 210000001789 adipocyte Anatomy 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 230000004071 biological effect Effects 0.000 description 3
• 230000033228 biological regulation Effects 0.000 description 3
• 210000001715 carotid artery Anatomy 0.000 description 3
• 238000005119 centrifugation Methods 0.000 description 3
• RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 3
• 239000005516 coenzyme A Substances 0.000 description 3
• 229940093530 coenzyme a Drugs 0.000 description 3
• 238000002425 crystallisation Methods 0.000 description 3
• 230000008025 crystallization Effects 0.000 description 3
• 230000001186 cumulative effect Effects 0.000 description 3
• 230000001120 cytoprotective effect Effects 0.000 description 3
• NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 3
• 230000003247 decreasing effect Effects 0.000 description 3
• KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 3
• 235000014113 dietary fatty acids Nutrition 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 239000000194 fatty acid Substances 0.000 description 3
• 229930195729 fatty acid Natural products 0.000 description 3
• 150000004665 fatty acids Chemical class 0.000 description 3
• 244000144993 groups of animals Species 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 210000002216 heart Anatomy 0.000 description 3
• 231100000234 hepatic damage Toxicity 0.000 description 3
• 208000006454 hepatitis Diseases 0.000 description 3
• 231100000283 hepatitis Toxicity 0.000 description 3
• 231100000304 hepatotoxicity Toxicity 0.000 description 3
• 230000007686 hepatotoxicity Effects 0.000 description 3
• 230000001146 hypoxic effect Effects 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000010354 integration Effects 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 231100000225 lethality Toxicity 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 230000008818 liver damage Effects 0.000 description 3
• 238000004519 manufacturing process Methods 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• 210000003205 muscle Anatomy 0.000 description 3
• 230000035772 mutation Effects 0.000 description 3
• 208000010125 myocardial infarction Diseases 0.000 description 3
• 210000002569 neuron Anatomy 0.000 description 3
• 230000003961 neuronal insult Effects 0.000 description 3
• 239000002858 neurotransmitter agent Substances 0.000 description 3
• 229960000689 nevirapine Drugs 0.000 description 3
• 239000011570 nicotinamide Substances 0.000 description 3
• 230000001883 nitrergic effect Effects 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• 229960002748 norepinephrine Drugs 0.000 description 3
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 3
• 150000003833 nucleoside derivatives Chemical class 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
• 239000013612 plasmid Substances 0.000 description 3
• 230000001681 protective effect Effects 0.000 description 3
• 239000003642 reactive oxygen metabolite Substances 0.000 description 3
• 238000006798 ring closing metathesis reaction Methods 0.000 description 3
• 230000035945 sensitivity Effects 0.000 description 3
• 210000002027 skeletal muscle Anatomy 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 230000035882 stress Effects 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 125000003396 thiol group Chemical group [H]S* 0.000 description 3
• 230000000451 tissue damage Effects 0.000 description 3
• 231100000827 tissue damage Toxicity 0.000 description 3
• 238000013518 transcription Methods 0.000 description 3
• 230000035897 transcription Effects 0.000 description 3
• 238000011830 transgenic mouse model Methods 0.000 description 3
• 241001430294 unidentified retrovirus Species 0.000 description 3
• 238000005303 weighing Methods 0.000 description 3
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
• HBJUQLMVCIEESP-UHFFFAOYSA-N 2,5-dihydro-1,2,4-oxadiazole Chemical compound C1NC=NO1 HBJUQLMVCIEESP-UHFFFAOYSA-N 0.000 description 2
• UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical compound CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 description 2
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical group NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• 206010003210 Arteriosclerosis Diseases 0.000 description 2
• 102100030907 Aryl hydrocarbon receptor nuclear translocator Human genes 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
• 101000690445 Caenorhabditis elegans Aryl hydrocarbon receptor nuclear translocator homolog Proteins 0.000 description 2
• 108090000312 Calcium Channels Proteins 0.000 description 2
• 102000003922 Calcium Channels Human genes 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• WDGNTLLMNSTYEC-UHFFFAOYSA-N Cl.Cl.O=C1NC=NO1 Chemical compound Cl.Cl.O=C1NC=NO1 WDGNTLLMNSTYEC-UHFFFAOYSA-N 0.000 description 2
• 241001573498 Compacta Species 0.000 description 2
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
• 102000003849 Cytochrome P450 Human genes 0.000 description 2
• 206010014824 Endotoxic shock Diseases 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 108010024636 Glutathione Proteins 0.000 description 2
• 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 2
• 206010019280 Heart failures Diseases 0.000 description 2
• RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
• 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 2
• 108010033040 Histones Proteins 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000793115 Homo sapiens Aryl hydrocarbon receptor nuclear translocator Proteins 0.000 description 2
• 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 2
• 208000001953 Hypotension Diseases 0.000 description 2
• 206010061216 Infarction Diseases 0.000 description 2
• 229940122355 Insulin sensitizer Drugs 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• 239000005089 Luciferase Substances 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• 238000011785 NMRI mouse Methods 0.000 description 2
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
• 208000008589 Obesity Diseases 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• 108700008625 Reporter Genes Proteins 0.000 description 2
• 102000007156 Resistin Human genes 0.000 description 2
• 108010047909 Resistin Proteins 0.000 description 2
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 229940123464 Thiazolidinedione Drugs 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• 108020000999 Viral RNA Proteins 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• 230000036982 action potential Effects 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 230000006978 adaptation Effects 0.000 description 2
• 229960005305 adenosine Drugs 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 230000003288 anthiarrhythmic effect Effects 0.000 description 2
• 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 2
• 230000000840 anti-viral effect Effects 0.000 description 2
• 206010003119 arrhythmia Diseases 0.000 description 2
• 230000006793 arrhythmia Effects 0.000 description 2
• 208000011775 arteriosclerosis disease Diseases 0.000 description 2
• 210000001367 artery Anatomy 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• 230000002238 attenuated effect Effects 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 244000309466 calf Species 0.000 description 2
• 239000001569 carbon dioxide Substances 0.000 description 2
• 229910002092 carbon dioxide Inorganic materials 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 230000001364 causal effect Effects 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000005779 cell damage Effects 0.000 description 2
• 208000037887 cell injury Diseases 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 2
• 229960005091 chloramphenicol Drugs 0.000 description 2
• 235000012000 cholesterol Nutrition 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 208000029078 coronary artery disease Diseases 0.000 description 2
• 125000000753 cycloalkyl group Chemical group 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 235000005911 diet Nutrition 0.000 description 2
• 230000037213 diet Effects 0.000 description 2
• 208000035475 disorder Diseases 0.000 description 2
• AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 2
• 210000005064 dopaminergic neuron Anatomy 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 230000000667 effect on insulin Effects 0.000 description 2
• 230000005684 electric field Effects 0.000 description 2
• 230000002708 enhancing effect Effects 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000012894 fetal calf serum Substances 0.000 description 2
• 239000000835 fiber Substances 0.000 description 2
• 230000002600 fibrillogenic effect Effects 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 235000021588 free fatty acids Nutrition 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 229960003180 glutathione Drugs 0.000 description 2
• 230000026030 halogenation Effects 0.000 description 2
• 238000005658 halogenation reaction Methods 0.000 description 2
• BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 2
• 230000009931 harmful effect Effects 0.000 description 2
• 230000003054 hormonal effect Effects 0.000 description 2
• 230000002218 hypoglycaemic effect Effects 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 239000000411 inducer Substances 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 210000004153 islets of langerhan Anatomy 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 229960003350 isoniazid Drugs 0.000 description 2
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 210000004731 jugular vein Anatomy 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 210000003141 lower extremity Anatomy 0.000 description 2
• 238000003670 luciferase enzyme activity assay Methods 0.000 description 2
• 238000004020 luminiscence type Methods 0.000 description 2
• 239000012139 lysis buffer Substances 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
• 108020004999 messenger RNA Proteins 0.000 description 2
• 230000002635 muscarinergic effect Effects 0.000 description 2
• 230000002107 myocardial effect Effects 0.000 description 2
• 208000031225 myocardial ischemia Diseases 0.000 description 2
• 230000005876 negative regulation of fatty acid oxidation Effects 0.000 description 2
• 210000001577 neostriatum Anatomy 0.000 description 2
• 230000001537 neural effect Effects 0.000 description 2
• 230000016273 neuron death Effects 0.000 description 2
• 235000005152 nicotinamide Nutrition 0.000 description 2
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
• BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide 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](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000002773 nucleotide Substances 0.000 description 2
• 125000003729 nucleotide group Chemical group 0.000 description 2
• 208000030212 nutrition disease Diseases 0.000 description 2
• 235000020824 obesity Nutrition 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 210000000578 peripheral nerve Anatomy 0.000 description 2
• 230000004526 pharmaceutical effect Effects 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 239000008363 phosphate buffer Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 230000000291 postprandial effect Effects 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 210000004129 prosencephalon Anatomy 0.000 description 2
• 230000004224 protection Effects 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 235000008160 pyridoxine Nutrition 0.000 description 2
• 239000011677 pyridoxine Substances 0.000 description 2
• 238000005956 quaternization reaction Methods 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 230000009257 reactivity Effects 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 230000000284 resting effect Effects 0.000 description 2
• 102220020162 rs397508045 Human genes 0.000 description 2
• 230000001235 sensitizing effect Effects 0.000 description 2
• 230000035939 shock Effects 0.000 description 2
• 101150062190 sod1 gene Proteins 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 210000003523 substantia nigra Anatomy 0.000 description 2
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
• 230000001960 triggered effect Effects 0.000 description 2
• 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 208000019553 vascular disease Diseases 0.000 description 2
• 230000000304 vasodilatating effect Effects 0.000 description 2
• 206010047302 ventricular tachycardia Diseases 0.000 description 2
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
• 229960004528 vincristine Drugs 0.000 description 2
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
• 229940011671 vitamin b6 Drugs 0.000 description 2
• 239000008096 xylene Substances 0.000 description 2
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
• PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
• VOYADQIFGGIKAT-UHFFFAOYSA-N 1,3-dibutyl-4-hydroxy-2,6-dioxopyrimidine-5-carboximidamide Chemical compound CCCCn1c(O)c(C(N)=N)c(=O)n(CCCC)c1=O VOYADQIFGGIKAT-UHFFFAOYSA-N 0.000 description 1
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
• YMUIALJGRCXTBP-UHFFFAOYSA-N 1-chloro-3-piperidin-1-ylpropan-2-ol;hydrochloride Chemical compound Cl.ClCC(O)CN1CCCCC1 YMUIALJGRCXTBP-UHFFFAOYSA-N 0.000 description 1
• VTDIWMPYBAVEDY-UHFFFAOYSA-N 1-propylpiperidine Chemical compound CCCN1CCCCC1 VTDIWMPYBAVEDY-UHFFFAOYSA-N 0.000 description 1
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
• TZDPJNSHSWMCPN-UHFFFAOYSA-N 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 TZDPJNSHSWMCPN-UHFFFAOYSA-N 0.000 description 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• HPYLZSUEFFQHRS-UHFFFAOYSA-N 2h-1,2,4-oxadiazine Chemical compound N1OC=CN=C1 HPYLZSUEFFQHRS-UHFFFAOYSA-N 0.000 description 1
• QMEQBOSUJUOXMX-UHFFFAOYSA-N 2h-oxadiazine Chemical group N1OC=CC=N1 QMEQBOSUJUOXMX-UHFFFAOYSA-N 0.000 description 1
• MNIQECRMTVGZBM-UHFFFAOYSA-N 3-(1-methylpyrrolidin-2-yl)pyridine;7h-purin-6-amine Chemical compound NC1=NC=NC2=C1NC=N2.CN1CCCC1C1=CC=CN=C1 MNIQECRMTVGZBM-UHFFFAOYSA-N 0.000 description 1
• GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
• CTQPPUPWHLGKOB-UHFFFAOYSA-N 4h-oxadiazol-5-one Chemical compound O=C1CN=NO1 CTQPPUPWHLGKOB-UHFFFAOYSA-N 0.000 description 1
• PWJFNRJRHXWEPT-UHFFFAOYSA-N ADP ribose Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OCC(O)C(O)C(O)C=O)C(O)C1O PWJFNRJRHXWEPT-UHFFFAOYSA-N 0.000 description 1
• SRNWOUGRCWSEMX-TYASJMOZSA-N ADP-D-ribose Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)N)OP(O)(=O)OP(O)(=O)OC[C@H]1OC(O)[C@H](O)[C@@H]1O SRNWOUGRCWSEMX-TYASJMOZSA-N 0.000 description 1
• 229930024421 Adenine Natural products 0.000 description 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 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
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 206010002660 Anoxia Diseases 0.000 description 1
• 241000976983 Anoxia Species 0.000 description 1
• 206010003175 Arterial spasm Diseases 0.000 description 1
• 206010003225 Arteriospasm coronary Diseases 0.000 description 1
• 229930003347 Atropine Natural products 0.000 description 1
• 238000012935 Averaging Methods 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 208000012639 Balance disease Diseases 0.000 description 1
• 108010027344 Basic Helix-Loop-Helix Transcription Factors Proteins 0.000 description 1
• 102000018720 Basic Helix-Loop-Helix Transcription Factors Human genes 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 206010006100 Bradykinesia Diseases 0.000 description 1
• 101100407073 Caenorhabditis elegans parp-1 gene Proteins 0.000 description 1
• LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 description 1
• 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 description 1
• 101001061353 Chattonella marina var. antiqua Glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 1
• 108020004638 Circular DNA Proteins 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 208000001778 Coronary Occlusion Diseases 0.000 description 1
• 206010011086 Coronary artery occlusion Diseases 0.000 description 1
• FCKYPQBAHLOOJQ-UHFFFAOYSA-N Cyclohexane-1,2-diaminetetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)C1CCCCC1N(CC(O)=O)CC(O)=O FCKYPQBAHLOOJQ-UHFFFAOYSA-N 0.000 description 1
• FMGYKKMPNATWHP-UHFFFAOYSA-N Cyperquat Chemical compound C1=C[N+](C)=CC=C1C1=CC=CC=C1 FMGYKKMPNATWHP-UHFFFAOYSA-N 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
• 108090000323 DNA Topoisomerases Proteins 0.000 description 1
• 102000003915 DNA Topoisomerases Human genes 0.000 description 1
• 231100001074 DNA strand break Toxicity 0.000 description 1
• MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 1
• 244000000626 Daucus carota Species 0.000 description 1
• 235000002767 Daucus carota Nutrition 0.000 description 1
• CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-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
• 206010061819 Disease recurrence Diseases 0.000 description 1
• SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 208000005189 Embolism Diseases 0.000 description 1
• 102000003951 Erythropoietin Human genes 0.000 description 1
• 108090000394 Erythropoietin Proteins 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 102000018711 Facilitative Glucose Transport Proteins Human genes 0.000 description 1
• BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 108091052347 Glucose transporter family Proteins 0.000 description 1
• JMBQKKAJIKAWKF-UHFFFAOYSA-N Glutethimide Chemical compound C=1C=CC=CC=1C1(CC)CCC(=O)NC1=O JMBQKKAJIKAWKF-UHFFFAOYSA-N 0.000 description 1
• 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 208000000857 Hepatic Insufficiency Diseases 0.000 description 1
• 206010019663 Hepatic failure Diseases 0.000 description 1
• 102000006947 Histones Human genes 0.000 description 1
• 101001113483 Homo sapiens Poly [ADP-ribose] polymerase 1 Proteins 0.000 description 1
• 101100149812 Homo sapiens SOD1 gene Proteins 0.000 description 1
• 102000013266 Human Regular Insulin Human genes 0.000 description 1
• 108010090613 Human Regular Insulin Proteins 0.000 description 1
• RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 208000006083 Hypokinesia Diseases 0.000 description 1
• 206010021033 Hypomenorrhoea Diseases 0.000 description 1
• 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
• 108010061833 Integrases Proteins 0.000 description 1
• 102000015696 Interleukins Human genes 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• 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 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 208000019430 Motor disease Diseases 0.000 description 1
• 208000002740 Muscle Rigidity Diseases 0.000 description 1
• 206010028289 Muscle atrophy Diseases 0.000 description 1
• 208000029549 Muscle injury Diseases 0.000 description 1
• 208000021642 Muscular disease Diseases 0.000 description 1
• 206010028372 Muscular weakness Diseases 0.000 description 1
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 229930193140 Neomycin Natural products 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 206010056677 Nerve degeneration Diseases 0.000 description 1
• 208000028389 Nerve injury Diseases 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 206010029350 Neurotoxicity Diseases 0.000 description 1
• 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
• 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
• 229940123921 Nitric oxide synthase inhibitor Drugs 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• 102000007999 Nuclear Proteins Human genes 0.000 description 1
• 108010089610 Nuclear Proteins Proteins 0.000 description 1
• KKTNHUJUXUYLDY-UHFFFAOYSA-N O1C(=O)N(CC(CCl)O)C(C=CC=2C=CC=CC=2)=N1 Chemical compound O1C(=O)N(CC(CCl)O)C(C=CC=2C=CC=CC=2)=N1 KKTNHUJUXUYLDY-UHFFFAOYSA-N 0.000 description 1
• 241000283977 Oryctolagus Species 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 206010034277 Pemphigoid Diseases 0.000 description 1
• 241000721454 Pemphigus Species 0.000 description 1
• 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 description 1
• 108091026813 Poly(ADPribose) Proteins 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 208000004880 Polyuria Diseases 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 241001340896 Pyralis Species 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 206010058156 Reperfusion arrhythmia Diseases 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 102100022340 SHC-transforming protein 1 Human genes 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• 108700043492 SprD Proteins 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
• UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 206010044221 Toxic encephalopathy Diseases 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• 239000007997 Tricine buffer Substances 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
• 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 206010047115 Vasculitis Diseases 0.000 description 1
• 108020005202 Viral DNA Proteins 0.000 description 1
• 206010047642 Vitiligo Diseases 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• JUGOREOARAHOCO-UHFFFAOYSA-M acetylcholine chloride Chemical compound [Cl-].CC(=O)OCC[N+](C)(C)C JUGOREOARAHOCO-UHFFFAOYSA-M 0.000 description 1
• 229960004266 acetylcholine chloride Drugs 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 208000038016 acute inflammation Diseases 0.000 description 1
• 230000006022 acute inflammation Effects 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 230000008649 adaptation response Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 229960000643 adenine Drugs 0.000 description 1
• TTWYZDPBDWHJOR-IDIVVRGQSA-L adenosine triphosphate disodium Chemical compound [Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O TTWYZDPBDWHJOR-IDIVVRGQSA-L 0.000 description 1
• 210000000577 adipose tissue Anatomy 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 229940035676 analgesics Drugs 0.000 description 1
• 230000003872 anastomosis Effects 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 230000007953 anoxia Effects 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• 230000003257 anti-anginal effect Effects 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 230000002686 anti-diuretic effect Effects 0.000 description 1
• 230000036436 anti-hiv Effects 0.000 description 1
• 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 239000003416 antiarrhythmic agent Substances 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 239000003435 antirheumatic agent Substances 0.000 description 1
• 210000000709 aorta Anatomy 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 230000004872 arterial blood pressure Effects 0.000 description 1
• 206010003230 arteritis Diseases 0.000 description 1
• RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
• 229960000396 atropine Drugs 0.000 description 1
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 229940049706 benzodiazepine Drugs 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 238000011138 biotechnological process Methods 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 210000000133 brain stem Anatomy 0.000 description 1
• 238000009395 breeding Methods 0.000 description 1
• 230000001488 breeding effect Effects 0.000 description 1
• 208000000594 bullous pemphigoid Diseases 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 230000023852 carbohydrate metabolic process Effects 0.000 description 1
• 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• HDFRDWFLWVCOGP-UHFFFAOYSA-N carbonothioic O,S-acid Chemical class OC(S)=O HDFRDWFLWVCOGP-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 206010061592 cardiac fibrillation Diseases 0.000 description 1
• 210000004413 cardiac myocyte Anatomy 0.000 description 1
• 229960004203 carnitine Drugs 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 150000003943 catecholamines Chemical class 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 210000003710 cerebral cortex Anatomy 0.000 description 1
• 230000001767 chemoprotection Effects 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 230000001713 cholinergic effect Effects 0.000 description 1
• 208000037516 chromosome inversion disease Diseases 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 230000006020 chronic inflammation Effects 0.000 description 1
• 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 description 1
• YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
• 229950009226 ciglitazone Drugs 0.000 description 1
• 230000007012 clinical effect Effects 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000000254 damaging effect Effects 0.000 description 1
• 229960000860 dapsone Drugs 0.000 description 1
• 230000002498 deadly effect Effects 0.000 description 1
• 230000007123 defense Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 229940120124 dichloroacetate Drugs 0.000 description 1
• JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
• KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• 230000003467 diminishing effect Effects 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• VXIHRIQNJCRFQX-UHFFFAOYSA-K disodium aurothiomalate Chemical compound [Na+].[Na+].[O-]C(=O)CC(S[Au])C([O-])=O VXIHRIQNJCRFQX-UHFFFAOYSA-K 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 229910000397 disodium phosphate Inorganic materials 0.000 description 1
• 235000019800 disodium phosphate Nutrition 0.000 description 1
• 229960002563 disulfiram Drugs 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 238000007877 drug screening Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 208000030172 endocrine system disease Diseases 0.000 description 1
• 230000003511 endothelial effect Effects 0.000 description 1
• 230000002327 eosinophilic effect Effects 0.000 description 1
• 238000011067 equilibration Methods 0.000 description 1
• 210000003743 erythrocyte Anatomy 0.000 description 1
• 229940105423 erythropoietin Drugs 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• 230000001610 euglycemic effect Effects 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 210000001105 femoral artery Anatomy 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000007941 film coated tablet Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 230000009760 functional impairment Effects 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 230000004153 glucose metabolism Effects 0.000 description 1
• 230000004190 glucose uptake Effects 0.000 description 1
• 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
• 230000002414 glycolytic effect Effects 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• ACGDKVXYNVEAGU-UHFFFAOYSA-N guanethidine Chemical compound NC(N)=NCCN1CCCCCCC1 ACGDKVXYNVEAGU-UHFFFAOYSA-N 0.000 description 1
• 229960003602 guanethidine Drugs 0.000 description 1
• 150000008282 halocarbons Chemical class 0.000 description 1
• 229960003132 halothane Drugs 0.000 description 1
• 238000011597 hartley guinea pig Methods 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 230000007866 hepatic necrosis Effects 0.000 description 1
• 206010019692 hepatic necrosis Diseases 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 230000002443 hepatoprotective effect Effects 0.000 description 1
• 230000000971 hippocampal effect Effects 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• 238000010562 histological examination Methods 0.000 description 1
• 238000000265 homogenisation Methods 0.000 description 1
• 229940038563 human regular insulin Drugs 0.000 description 1
• 229960002474 hydralazine Drugs 0.000 description 1
• TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 1
• 230000000910 hyperinsulinemic effect Effects 0.000 description 1
• 230000035873 hypermotility Effects 0.000 description 1
• 230000036543 hypotension Effects 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 150000002465 imidoyl halides Chemical class 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 238000005470 impregnation Methods 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 230000007574 infarction Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 230000003914 insulin secretion Effects 0.000 description 1
• 230000002608 insulinlike Effects 0.000 description 1
• 229940047122 interleukins Drugs 0.000 description 1
• 208000028774 intestinal disease Diseases 0.000 description 1
• 208000037906 ischaemic injury Diseases 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 208000012866 low blood pressure Diseases 0.000 description 1
• 206010025135 lupus erythematosus Diseases 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000005226 mechanical processes and functions Effects 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 210000001259 mesencephalon Anatomy 0.000 description 1
• 208000030159 metabolic disease Diseases 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 150000001247 metal acetylides Chemical class 0.000 description 1
• WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
• VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
• 229960000282 metronidazole Drugs 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 210000003470 mitochondria Anatomy 0.000 description 1
• 230000002438 mitochondrial effect Effects 0.000 description 1
• 210000001700 mitochondrial membrane Anatomy 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 150000004712 monophosphates Chemical class 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 239000004570 mortar (masonry) Substances 0.000 description 1
• 230000004899 motility Effects 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 230000020763 muscle atrophy Effects 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 201000000585 muscular atrophy Diseases 0.000 description 1
• 230000036473 myasthenia Effects 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 230000017095 negative regulation of cell growth Effects 0.000 description 1
• 229960004927 neomycin Drugs 0.000 description 1
• 230000008035 nerve activity Effects 0.000 description 1
• 230000008764 nerve damage Effects 0.000 description 1
• 210000004126 nerve fiber Anatomy 0.000 description 1
• 210000000944 nerve tissue Anatomy 0.000 description 1
• 230000000626 neurodegenerative effect Effects 0.000 description 1
• 230000002644 neurohormonal effect Effects 0.000 description 1
• 230000003955 neuronal function Effects 0.000 description 1
• 230000000324 neuroprotective effect Effects 0.000 description 1
• 230000002887 neurotoxic effect Effects 0.000 description 1
• 230000007135 neurotoxicity Effects 0.000 description 1
• 231100000228 neurotoxicity Toxicity 0.000 description 1
• 238000006386 neutralization reaction Methods 0.000 description 1
• 229960003966 nicotinamide Drugs 0.000 description 1
• 229960000715 nimodipine Drugs 0.000 description 1
• 239000002840 nitric oxide donor Substances 0.000 description 1
• 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 1
• 229920001220 nitrocellulos Polymers 0.000 description 1
• NXFQHRVNIOXGAQ-YCRREMRBSA-N nitrofurantoin Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)NC(=O)C1 NXFQHRVNIOXGAQ-YCRREMRBSA-N 0.000 description 1
• 229960000564 nitrofurantoin Drugs 0.000 description 1
• 229940120480 nitrogen 30 % Drugs 0.000 description 1
• 239000001272 nitrous oxide Substances 0.000 description 1
• 229960001730 nitrous oxide Drugs 0.000 description 1
• 230000001129 nonadrenergic effect Effects 0.000 description 1
• 235000021590 normal diet Nutrition 0.000 description 1
• 238000010606 normalization Methods 0.000 description 1
• 229940127073 nucleoside analogue Drugs 0.000 description 1
• 125000003835 nucleoside group Chemical class 0.000 description 1
• 208000019180 nutritional disease Diseases 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 239000003791 organic solvent mixture Substances 0.000 description 1
• 231100000927 organotoxic Toxicity 0.000 description 1
• 238000012261 overproduction Methods 0.000 description 1
• 230000036284 oxygen consumption Effects 0.000 description 1
• 238000004806 packaging method and process Methods 0.000 description 1
• 125000000913 palmityl 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])C([H])([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
• INFDPOAKFNIJBF-UHFFFAOYSA-N paraquat Chemical compound C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 INFDPOAKFNIJBF-UHFFFAOYSA-N 0.000 description 1
• 230000001734 parasympathetic effect Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 101150063226 parp-1 gene Proteins 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000001991 pathophysiological effect Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229960001412 pentobarbital Drugs 0.000 description 1
• 238000005502 peroxidation Methods 0.000 description 1
• 239000003614 peroxisome proliferator Substances 0.000 description 1
• 150000004965 peroxy acids Chemical group 0.000 description 1
• 239000000575 pesticide Substances 0.000 description 1
• 230000009038 pharmacological inhibition Effects 0.000 description 1
• 230000000079 pharmacotherapeutic effect Effects 0.000 description 1
• 208000028591 pheochromocytoma Diseases 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 239000013600 plasmid vector Substances 0.000 description 1
• 238000007747 plating Methods 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 230000001323 posttranslational effect Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000002028 premature Effects 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 230000002633 protecting effect Effects 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000004060 quinone imines Chemical class 0.000 description 1
• 239000012857 radioactive material Substances 0.000 description 1
• 238000003127 radioimmunoassay Methods 0.000 description 1
• 231100000272 reduced body weight Toxicity 0.000 description 1
• 239000013558 reference substance Substances 0.000 description 1
• 230000013333 regulation of fatty acid metabolic process Effects 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 238000003571 reporter gene assay Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000020874 response to hypoxia Effects 0.000 description 1
• 230000000979 retarding effect Effects 0.000 description 1
• 230000001177 retroviral effect Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 238000010825 rotarod performance test Methods 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 210000003497 sciatic nerve Anatomy 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 238000004062 sedimentation Methods 0.000 description 1
• 210000001044 sensory neuron Anatomy 0.000 description 1
• 201000005572 sensory peripheral neuropathy Diseases 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 229960001315 sodium aurothiomalate Drugs 0.000 description 1
• 229940054269 sodium pyruvate Drugs 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 210000003594 spinal ganglia Anatomy 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 125000004079 stearyl 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])C([H])([H])C([H])([H])C([H])([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
• 239000008174 sterile solution Substances 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 210000000225 synapse Anatomy 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 238000010257 thawing Methods 0.000 description 1
• 150000001467 thiazolidinediones Chemical class 0.000 description 1
• 150000003548 thiazolidines Chemical class 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 230000017105 transposition Effects 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
• 229960004799 tryptophan Drugs 0.000 description 1
• 230000001196 vasorelaxation Effects 0.000 description 1
• 208000003663 ventricular fibrillation Diseases 0.000 description 1
• 230000029812 viral genome replication Effects 0.000 description 1
• 210000002845 virion Anatomy 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1