JP2000507929A - ジスムタチンスーパーオキシドの触媒として有効な窒素含有大環状化合物配位子を持つ鉄錯体 - Google Patents

ジスムタチンスーパーオキシドの触媒として有効な窒素含有大環状化合物配位子を持つ鉄錯体

Info

Publication number: JP2000507929A
Authority: JP; Japan
Prior art keywords: ion; alkyl; acid; aryl; solution
Prior art date: 1996-03-13
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Pending

Application number

JP9532095A

Other languages

English (en)

Japanese (ja)

Inventor

リレイ，デニス，ピー．

Original Assignee

モンサントカンパニー

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-03-13

Filing date

1997-03-11

Publication date

2000-06-27

1997-03-11 Application filed by モンサントカンパニー filed Critical モンサントカンパニー

2000-06-27 Publication of JP2000507929A publication Critical patent/JP2000507929A/ja

Status Pending legal-status Critical Current

Links

-1 Nitrogen-Containing Macrocycle Chemical class 0.000 title claims description 151
OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 title claims description 38
239000003446 ligand Substances 0.000 title claims description 36
239000003054 catalyst Substances 0.000 title description 7
150000002505 iron Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 53
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
208000035475 disorder Diseases 0.000 claims abstract description 7
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 6
206010063837 Reperfusion injury Diseases 0.000 claims abstract description 6
208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 5
206010008111 Cerebral haemorrhage Diseases 0.000 claims abstract description 4
208000028867 ischemia Diseases 0.000 claims abstract description 4
239000007800 oxidant agent Substances 0.000 claims abstract description 3
230000000451 tissue damage Effects 0.000 claims abstract description 3
231100000827 tissue damage Toxicity 0.000 claims abstract description 3
230000001590 oxidative effect Effects 0.000 claims abstract 2
238000006243 chemical reaction Methods 0.000 claims description 53
125000000217 alkyl group Chemical group 0.000 claims description 47
238000000034 method Methods 0.000 claims description 44
239000002253 acid Substances 0.000 claims description 43
239000000203 mixture Substances 0.000 claims description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
229920006395 saturated elastomer Polymers 0.000 claims description 29
239000001257 hydrogen Substances 0.000 claims description 24
229910052739 hydrogen Inorganic materials 0.000 claims description 24
150000002500 ions Chemical class 0.000 claims description 22
125000004432 carbon atom Chemical group C* 0.000 claims description 19
235000001014 amino acid Nutrition 0.000 claims description 18
150000001450 anions Chemical class 0.000 claims description 17
229910052799 carbon Inorganic materials 0.000 claims description 16
125000000753 cycloalkyl group Chemical group 0.000 claims description 15
201000010099 disease Diseases 0.000 claims description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
150000001413 amino acids Chemical class 0.000 claims description 13
229910052757 nitrogen Inorganic materials 0.000 claims description 13
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 12
150000002678 macrocyclic compounds Chemical class 0.000 claims description 11
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 10
150000001721 carbon Chemical group 0.000 claims description 10
238000007323 disproportionation reaction Methods 0.000 claims description 10
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 9
150000002431 hydrogen Chemical class 0.000 claims description 9
239000004202 carbamide Substances 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 7
239000003981 vehicle Substances 0.000 claims description 7
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 6
230000006378 damage Effects 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
238000011282 treatment Methods 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 5
125000000304 alkynyl group Chemical group 0.000 claims description 5
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
230000000302 ischemic effect Effects 0.000 claims description 5
210000000056 organ Anatomy 0.000 claims description 5
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 5
MDDUHVRJJAFRAU-YZNNVMRBSA-N tert-butyl-[(1r,3s,5z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-4-methylidenecyclohexyl]oxy-dimethylsilane Chemical compound C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C(=C)\C1=C/CP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 MDDUHVRJJAFRAU-YZNNVMRBSA-N 0.000 claims description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
125000002877 alkyl aryl group Chemical group 0.000 claims description 4
125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
DKSMCEUSSQTGBK-UHFFFAOYSA-M bromite Chemical compound [O-]Br=O DKSMCEUSSQTGBK-UHFFFAOYSA-M 0.000 claims description 4
238000009472 formulation Methods 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
208000014674 injury Diseases 0.000 claims description 4
239000003456 ion exchange resin Substances 0.000 claims description 4
229920003303 ion-exchange polymer Polymers 0.000 claims description 4
230000001404 mediated effect Effects 0.000 claims description 4
229910017604 nitric acid Inorganic materials 0.000 claims description 4
231100000252 nontoxic Toxicity 0.000 claims description 4
230000003000 nontoxic effect Effects 0.000 claims description 4
201000008482 osteoarthritis Diseases 0.000 claims description 4
229910000073 phosphorus hydride Inorganic materials 0.000 claims description 4
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 3
206010027476 Metastases Diseases 0.000 claims description 3
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
208000007536 Thrombosis Diseases 0.000 claims description 3
206010052779 Transplant rejections Diseases 0.000 claims description 3
239000002671 adjuvant Substances 0.000 claims description 3
150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 3
235000008206 alpha-amino acids Nutrition 0.000 claims description 3
QBWCMBCROVPCKQ-UHFFFAOYSA-M chlorite Chemical compound [O-]Cl=O QBWCMBCROVPCKQ-UHFFFAOYSA-M 0.000 claims description 3
229940005993 chlorite ion Drugs 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
150000004820 halides Chemical class 0.000 claims description 3
239000012948 isocyanate Substances 0.000 claims description 3
150000002513 isocyanates Chemical class 0.000 claims description 3
230000009401 metastasis Effects 0.000 claims description 3
229940085991 phosphate ion Drugs 0.000 claims description 3
230000005855 radiation Effects 0.000 claims description 3
CVHZOJJKTDOEJC-UHFFFAOYSA-M 1,1-dioxo-1,2-benzothiazol-3-olate Chemical compound C1=CC=C2C([O-])=NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-M 0.000 claims description 2
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
208000005623 Carcinogenesis Diseases 0.000 claims description 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 claims description 2
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 2
206010033645 Pancreatitis Diseases 0.000 claims description 2
206010033647 Pancreatitis acute Diseases 0.000 claims description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims description 2
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 2
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
201000003229 acute pancreatitis Diseases 0.000 claims description 2
230000002776 aggregation Effects 0.000 claims description 2
238000004220 aggregation Methods 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
150000004789 alkyl aryl sulfoxides Chemical class 0.000 claims description 2
150000001356 alkyl thiols Chemical class 0.000 claims description 2
229910021529 ammonia Inorganic materials 0.000 claims description 2
150000001504 aryl thiols Chemical class 0.000 claims description 2
229940072107 ascorbate Drugs 0.000 claims description 2
235000010323 ascorbic acid Nutrition 0.000 claims description 2
239000011668 ascorbic acid Substances 0.000 claims description 2
239000008280 blood Substances 0.000 claims description 2
210000004369 blood Anatomy 0.000 claims description 2
230000036952 cancer formation Effects 0.000 claims description 2
231100000504 carcinogenesis Toxicity 0.000 claims description 2
XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 claims description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims description 2
229910001882 dioxygen Inorganic materials 0.000 claims description 2
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 2
OUUQCZGPVNCOIJ-UHFFFAOYSA-N hydroperoxyl Chemical group O[O] OUUQCZGPVNCOIJ-UHFFFAOYSA-N 0.000 claims description 2
GQZXNSPRSGFJLY-UHFFFAOYSA-N hydroxyphosphanone Chemical compound OP=O GQZXNSPRSGFJLY-UHFFFAOYSA-N 0.000 claims description 2
WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 claims description 2
229940005631 hypophosphite ion Drugs 0.000 claims description 2
150000002825 nitriles Chemical class 0.000 claims description 2
229940005654 nitrite ion Drugs 0.000 claims description 2
LLYCMZGLHLKPPU-UHFFFAOYSA-M perbromate Chemical compound [O-]Br(=O)(=O)=O LLYCMZGLHLKPPU-UHFFFAOYSA-M 0.000 claims description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 2
230000002265 prevention Effects 0.000 claims description 2
206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 2
208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 2
150000003573 thiols Chemical class 0.000 claims description 2
229940006280 thiosulfate ion Drugs 0.000 claims description 2
DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 claims description 2
230000008733 trauma Effects 0.000 claims description 2
239000001226 triphosphate Substances 0.000 claims description 2
235000011178 triphosphate Nutrition 0.000 claims description 2
239000000825 pharmaceutical preparation Substances 0.000 claims 5
OKQKDCXVLPGWPO-UHFFFAOYSA-N sulfanylidenephosphane Chemical compound S=P OKQKDCXVLPGWPO-UHFFFAOYSA-N 0.000 claims 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
208000003241 Fat Embolism Diseases 0.000 claims 1
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims 1
SSBRSHIQIANGKS-UHFFFAOYSA-N [amino(hydroxy)methylidene]azanium;hydrogen sulfate Chemical compound NC(N)=O.OS(O)(=O)=O SSBRSHIQIANGKS-UHFFFAOYSA-N 0.000 claims 1
125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
125000001769 aryl amino group Chemical group 0.000 claims 1
125000005361 aryl sulfoxide group Chemical group 0.000 claims 1
150000001540 azides Chemical class 0.000 claims 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
229910052794 bromium Inorganic materials 0.000 claims 1
125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 claims 1
239000012990 dithiocarbamate Substances 0.000 claims 1
239000003292 glue Substances 0.000 claims 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims 1
JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Chemical compound Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 claims 1
ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 claims 1
GRHBQAYDJPGGLF-UHFFFAOYSA-N isothiocyanic acid Chemical compound N=C=S GRHBQAYDJPGGLF-UHFFFAOYSA-N 0.000 claims 1
150000007524 organic acids Chemical class 0.000 claims 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims 1
230000000241 respiratory effect Effects 0.000 claims 1
125000000547 substituted alkyl group Chemical group 0.000 claims 1
230000000472 traumatic effect Effects 0.000 claims 1
102000019197 Superoxide Dismutase Human genes 0.000 abstract description 11
108010012715 Superoxide dismutase Proteins 0.000 abstract description 11
239000003814 drug Substances 0.000 abstract description 10
208000027866 inflammatory disease Diseases 0.000 abstract description 8
208000024891 symptom Diseases 0.000 abstract 1
239000000243 solution Substances 0.000 description 120
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
229910052717 sulfur Inorganic materials 0.000 description 52
239000007787 solid Substances 0.000 description 49
239000002904 solvent Substances 0.000 description 47
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
238000003756 stirring Methods 0.000 description 44
229910001868 water Inorganic materials 0.000 description 40
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
230000015572 biosynthetic process Effects 0.000 description 37
238000003786 synthesis reaction Methods 0.000 description 37
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 25
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 24
238000001914 filtration Methods 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
239000010410 layer Substances 0.000 description 21
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
239000000706 filtrate Substances 0.000 description 19
239000003921 oil Substances 0.000 description 19
235000019198 oils Nutrition 0.000 description 19
239000000047 product Substances 0.000 description 19
238000005160 1H NMR spectroscopy Methods 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
229940024606 amino acid Drugs 0.000 description 17
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
238000005481 NMR spectroscopy Methods 0.000 description 14
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 13
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
239000007864 aqueous solution Substances 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
239000000843 powder Substances 0.000 description 12
VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical class [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 11
229910052742 iron Inorganic materials 0.000 description 11
239000012300 argon atmosphere Substances 0.000 description 10
150000002506 iron compounds Chemical class 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
239000000284 extract Substances 0.000 description 9
CWNPOQFCIIFQDM-UHFFFAOYSA-N 3-nitrobenzyl alcohol Chemical compound OCC1=CC=CC([N+]([O-])=O)=C1 CWNPOQFCIIFQDM-UHFFFAOYSA-N 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
239000013078 crystal Substances 0.000 description 8
230000000694 effects Effects 0.000 description 8
150000004698 iron complex Chemical class 0.000 description 8
239000007788 liquid Substances 0.000 description 8
239000012298 atmosphere Substances 0.000 description 7
125000000392 cycloalkenyl group Chemical group 0.000 description 7
229940079593 drug Drugs 0.000 description 7
238000001035 drying Methods 0.000 description 7
239000006260 foam Substances 0.000 description 7
238000010992 reflux Methods 0.000 description 7
239000000725 suspension Substances 0.000 description 7
238000005406 washing Methods 0.000 description 7
239000007983 Tris buffer Substances 0.000 description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
239000000872 buffer Substances 0.000 description 6
239000012141 concentrate Substances 0.000 description 6
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238000002425 crystallisation Methods 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
150000004985 diamines Chemical group 0.000 description 6
238000004821 distillation Methods 0.000 description 6
239000012535 impurity Substances 0.000 description 6
238000012933 kinetic analysis Methods 0.000 description 6
230000003287 optical effect Effects 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 6
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 5
108010016626 Dipeptides Proteins 0.000 description 5
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
238000000605 extraction Methods 0.000 description 5
125000000524 functional group Chemical group 0.000 description 5
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
238000012986 modification Methods 0.000 description 5
230000004048 modification Effects 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
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238000000746 purification Methods 0.000 description 1
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238000010833 quantitative mass spectrometry Methods 0.000 description 1
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239000000377 silicon dioxide Substances 0.000 description 1
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
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KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
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238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
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235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000004001 thioalkyl group Chemical group 0.000 description 1
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000007070 tosylation reaction Methods 0.000 description 1
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230000001988 toxicity Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
239000004474 valine Substances 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
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238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D259/00—Heterocyclic compounds containing rings having more than four nitrogen atoms as the only ring hetero atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/02—Iron compounds
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/02—Iron compounds
- C07F15/025—Iron compounds without a metal-carbon linkage
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Wood Science & Technology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Epidemiology (AREA)
Zoology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Molecular Biology (AREA)
Vascular Medicine (AREA)
Biotechnology (AREA)
Immunology (AREA)
Microbiology (AREA)
Analytical Chemistry (AREA)
Physics & Mathematics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
General Engineering & Computer Science (AREA)
Genetics & Genomics (AREA)
Urology & Nephrology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Enzymes And Modification Thereof (AREA)

JP9532095A 1996-03-13 1997-03-11 ジスムタチンスーパーオキシドの触媒として有効な窒素含有大環状化合物配位子を持つ鉄錯体 Pending JP2000507929A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US61471096A	1996-03-13	1996-03-13
US08/614,710		1996-03-13
PCT/US1997/003348 WO1997033588A1 (en)	1996-03-13	1997-03-11	Iron complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide

Publications (1)

Publication Number	Publication Date
JP2000507929A true JP2000507929A (ja)	2000-06-27

Family

ID=24462404

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP9532095A Pending JP2000507929A (ja)	1996-03-13	1997-03-11	ジスムタチンスーパーオキシドの触媒として有効な窒素含有大環状化合物配位子を持つ鉄錯体

Country Status (10)

Country	Link
EP (1)	EP0888115A1 (cs)
JP (1)	JP2000507929A (cs)
KR (1)	KR19990087783A (cs)
AU (1)	AU2065697A (cs)
BR (1)	BR9707978A (cs)
CA (1)	CA2248964A1 (cs)
CZ (1)	CZ277698A3 (cs)
IL (1)	IL125993A0 (cs)
NO (1)	NO984165L (cs)
WO (1)	WO1997033588A1 (cs)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6127356A (en)	1993-10-15	2000-10-03	Duke University	Oxidant scavengers
DE69813898T2 (de)	1997-11-03	2004-03-11	Duke University	Substituierte porphyrinen
ATE312103T1 (de)	1999-01-25	2005-12-15	Nat Jewish Med & Res Center	Substituierte porphyrine und deren therapeutische verwendungen
ES2240101T3 (es)	1999-05-27	2005-10-16	Monsanto Company	Biomateriales modificados con mimeticos de superoxido dismutasa.
DE60235955D1 (de) *	2001-01-05	2010-05-27	Metaphore Pharmaceuticals Inc	Zusammensetzungen und verfahren zur erhöhung der zytokin-aktivität und zur behandlung der hypotension assoziiert mit der verabreichung von zytokinen
AU2002236861A1 (en) *	2001-01-26	2002-08-06	Metaphore Pharmaceuticals, Inc.	Method of treatment of neurodegenerative disorders using pentaaza-macrocyclic ligand complexes
EP1439842A4 (en)	2001-06-01	2009-09-02	Nat Jewish Med & Res Center	OXIDANT CAPTAIN FOR THE TREATMENT OF DIABETES OR FOR THE USE IN THE TRANSPLANTATION OR INDUCTION OF IMMUNOTOLERANE
WO2003103680A1 (en)	2002-06-07	2003-12-18	Duke University	Substituted porphyrins
US8468189B2 (en)	2006-11-08	2013-06-18	Okinawa Institute Of Science And Technology Promotion Corporation	Iterated variational regularization combined with componentwise regularization
DK2300003T3 (da)	2008-05-23	2014-05-26	Nat Jewish Health	Forbindelser til anvendelse i behandling af skade forbundet med eksponering for en alkylerende art

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE69224839T2 (de) *	1991-07-19	1998-10-08	Monsanto Co	Mangan-Komplexe mit Stickstoff enthaltenden makrozyklischen Liganden, wirksam als Superoxiddismutasekatalysatoren.
CZ307096A3 (en) *	1994-04-22	1997-09-17	Monsanto Co	Methods of video analysis by making use of metal complexes of nitrogen-containing macrocyclic ligands
US6525041B1 (en) *	1995-06-06	2003-02-25	Pharmacia Corporation	Manganese or iron complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide

1997
- 1997-03-11 CA CA002248964A patent/CA2248964A1/en not_active Abandoned
- 1997-03-11 WO PCT/US1997/003348 patent/WO1997033588A1/en not_active Ceased
- 1997-03-11 EP EP97908848A patent/EP0888115A1/en not_active Withdrawn
- 1997-03-11 KR KR1019980707264A patent/KR19990087783A/ko not_active Withdrawn
- 1997-03-11 IL IL12599397A patent/IL125993A0/xx unknown
- 1997-03-11 JP JP9532095A patent/JP2000507929A/ja active Pending
- 1997-03-11 AU AU20656/97A patent/AU2065697A/en not_active Abandoned
- 1997-03-11 CZ CZ982776A patent/CZ277698A3/cs unknown
- 1997-03-11 BR BR9707978A patent/BR9707978A/pt not_active Application Discontinuation
1998
- 1998-09-10 NO NO984165A patent/NO984165L/no unknown

Also Published As

Publication number	Publication date
CZ277698A3 (cs)	1999-02-17
BR9707978A (pt)	1999-07-27
WO1997033588A1 (en)	1997-09-18
AU2065697A (en)	1997-10-01
CA2248964A1 (en)	1997-09-18
NO984165D0 (no)	1998-09-10
KR19990087783A (ko)	1999-12-27
IL125993A0 (en)	1999-04-11
NO984165L (no)	1998-11-10
EP0888115A1 (en)	1999-01-07

Publication	Publication Date	Title
JP3155552B2 (ja)	2001-04-09	超酸化物の不均斉変化に有効な触媒としての窒素含有−大環状リガンドのマンガン錯体
US6204259B1 (en)	2001-03-20	Manganese complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide
US5610293A (en)	1997-03-11	Methods of preparing manganese complexes of nitrogen-containing macrocyclic ligands
US6525041B1 (en)	2003-02-25	Manganese or iron complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide
AU706642B2 (en)	1999-06-17	Diagnostic image analysis with metal complexes
JPH11511168A (ja)	1999-09-28	窒素含有大環状リガンドの金属錯体の生体分子結合体を使用する診断造影検査方法
JP2000508625A (ja)	2000-07-11	スーパーオキシドをジスムテートする触媒として有効な窒素含有大環状リガンドのマンガンまたは鉄錯体の生体分子結合体
CZ39898A3 (cs)	1998-07-15	Biokonjugáty manganových komplexů makrocyklických ligandů obsahujících dusík účinné jako katalyzátory dismutace superoxidu
US5721361A (en)	1998-02-24	Process for preparing substituted polyazamacrocycles
EP0888115A1 (en)	1999-01-07	Iron complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide
WO1997033588A9 (en)	1997-11-06	Iron complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide
MXPA98001322A (en)	1998-10-23	Bioconjugados de complejos de manganeso de ligandos macrociclicos containing nitrogen, effective as catalysts to dismute superox
KR0154346B1 (ko)	1998-12-01	슈퍼옥사이드의 불균환 촉매로서 효과적인 질소를 포함하는 마크로사이클릭 리간드의 망간 착물
MXPA98007449A (en)	1999-04-06	Complexes with iron of macrocyclic ligands containing nitrogen, effective as catalysts to dismute superox