JP2006502081A5 - - Google Patents

Info

Publication number

JP2006502081A5

JP2006502081A5 JP2003552281A JP2003552281A JP2006502081A5 JP 2006502081 A5 JP2006502081 A5 JP 2006502081A5 JP 2003552281 A JP2003552281 A JP 2003552281A JP 2003552281 A JP2003552281 A JP 2003552281A JP 2006502081 A5 JP2006502081 A5 JP 2006502081A5

Authority

JP

Japan

Prior art keywords

amino

patent document

composition according

acid

phenyl

Prior art date

2002-12-18

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

Links

• Espacenet
• Global Dossier
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• -1 1,3-propylene Chemical group 0.000 claims description 102
• 229920000768 polyamine Polymers 0.000 claims description 91
• 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 claims description 88
• 229910052757 nitrogen Inorganic materials 0.000 claims description 81
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 76
• GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 75
• XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 70
• 235000017471 coenzyme Q10 Nutrition 0.000 claims description 69
• ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 claims description 69
• 108020005196 Mitochondrial DNA Proteins 0.000 claims description 67
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 62
• 239000000203 mixture Substances 0.000 claims description 61
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 53
• 229910052698 phosphorus Inorganic materials 0.000 claims description 53
• 239000011574 phosphorus Chemical group 0.000 claims description 53
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 51
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 51
• 229910052799 carbon Inorganic materials 0.000 claims description 51
• 229910052717 sulfur Inorganic materials 0.000 claims description 51
• 239000011593 sulfur Chemical group 0.000 claims description 51
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 48
• 108010024636 Glutathione Proteins 0.000 claims description 45
• GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 43
• 229960003180 glutathione Drugs 0.000 claims description 42
• 150000001413 amino acids Chemical class 0.000 claims description 41
• 235000003969 glutathione Nutrition 0.000 claims description 41
• 125000003118 aryl group Chemical group 0.000 claims description 39
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 37
• 229930003427 Vitamin E Natural products 0.000 claims description 37
• 125000000217 alkyl group Chemical group 0.000 claims description 37
• WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 37
• 235000019165 vitamin E Nutrition 0.000 claims description 37
• 239000011709 vitamin E Substances 0.000 claims description 37
• ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 claims description 36
• LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims description 36
• TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims description 36
• 235000010323 ascorbic acid Nutrition 0.000 claims description 36
• 239000011668 ascorbic acid Substances 0.000 claims description 36
• 239000001257 hydrogen Substances 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• 229940116269 uric acid Drugs 0.000 claims description 36
• 229940046009 vitamin E Drugs 0.000 claims description 36
• 229940024606 amino acid Drugs 0.000 claims description 35
• 229960005070 ascorbic acid Drugs 0.000 claims description 35
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
• 229940011871 estrogen Drugs 0.000 claims description 35
• 239000000262 estrogen Substances 0.000 claims description 35
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 35
• 229960003080 taurine Drugs 0.000 claims description 35
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 34
• 229960004217 benzyl alcohol Drugs 0.000 claims description 34
• FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 claims description 34
• 229960003912 probucol Drugs 0.000 claims description 34
• AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims description 33
• FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 claims description 33
• ABSPRNADVQNDOU-UHFFFAOYSA-N Menaquinone 1 Natural products C1=CC=C2C(=O)C(CC=C(C)C)=C(C)C(=O)C2=C1 ABSPRNADVQNDOU-UHFFFAOYSA-N 0.000 claims description 33
• RDHQFKQIGNGIED-MRVPVSSYSA-N O-acetyl-L-carnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 claims description 33
• OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 claims description 33
• AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 33
• 235000013734 beta-carotene Nutrition 0.000 claims description 33
• 239000011648 beta-carotene Substances 0.000 claims description 33
• TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 claims description 33
• 229960002747 betacarotene Drugs 0.000 claims description 33
• FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 claims description 33
• 235000019136 lipoic acid Nutrition 0.000 claims description 33
• 235000019175 phylloquinone Nutrition 0.000 claims description 33
• SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 claims description 33
• 239000011772 phylloquinone Substances 0.000 claims description 33
• MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 claims description 33
• 229960001898 phytomenadione Drugs 0.000 claims description 33
• 229960002847 prasterone Drugs 0.000 claims description 33
• NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 claims description 33
• 229960002663 thioctic acid Drugs 0.000 claims description 33
• 229940035936 ubiquinone Drugs 0.000 claims description 33
• OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 claims description 33
• 229940087168 alpha tocopherol Drugs 0.000 claims description 32
• 229930003935 flavonoid Natural products 0.000 claims description 32
• 150000002215 flavonoids Chemical class 0.000 claims description 32
• 235000017173 flavonoids Nutrition 0.000 claims description 32
• 229960000984 tocofersolan Drugs 0.000 claims description 32
• 235000004835 α-tocopherol Nutrition 0.000 claims description 32
• 239000002076 α-tocopherol Substances 0.000 claims description 32
• 230000002438 mitochondrial effect Effects 0.000 claims description 31
• 239000011651 chromium Substances 0.000 claims description 28
• 125000000623 heterocyclic group Chemical group 0.000 claims description 28
• 229910052804 chromium Inorganic materials 0.000 claims description 27
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 27
• VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 26
• 230000005778 DNA damage Effects 0.000 claims description 25
• 231100000277 DNA damage Toxicity 0.000 claims description 25
• 229910019142 PO4 Inorganic materials 0.000 claims description 25
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 24
• 239000010452 phosphate Substances 0.000 claims description 24
• FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims description 23
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 23
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 22
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 21
• 229930195712 glutamate Natural products 0.000 claims description 21
• 150000003573 thiols Chemical class 0.000 claims description 21
• 230000006378 damage Effects 0.000 claims description 20
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 19
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 18
• 229910052742 iron Inorganic materials 0.000 claims description 18
• 229910052720 vanadium Inorganic materials 0.000 claims description 18
• LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 claims description 18
• 239000002872 contrast media Substances 0.000 claims description 16
• 230000007812 deficiency Effects 0.000 claims description 16
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 16
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
• OZOMQRBLCMDCEG-CHHVJCJISA-N 1-[(z)-[5-(4-nitrophenyl)furan-2-yl]methylideneamino]imidazolidine-2,4-dione Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(O1)=CC=C1\C=N/N1C(=O)NC(=O)C1 OZOMQRBLCMDCEG-CHHVJCJISA-N 0.000 claims description 14
• 229960001987 dantrolene Drugs 0.000 claims description 14
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
• HYPYXGZDOYTYDR-HAJWAVTHSA-N 2-methyl-3-[(2e,6e,10e,14e)-3,7,11,15,19-pentamethylicosa-2,6,10,14,18-pentaenyl]naphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 HYPYXGZDOYTYDR-HAJWAVTHSA-N 0.000 claims description 12
• JGPMMRGNQUBGND-UHFFFAOYSA-N idebenone Chemical compound COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O JGPMMRGNQUBGND-UHFFFAOYSA-N 0.000 claims description 12
• 229960004135 idebenone Drugs 0.000 claims description 12
• 235000019143 vitamin K2 Nutrition 0.000 claims description 12
• 239000011728 vitamin K2 Substances 0.000 claims description 12
• 229940041603 vitamin k 3 Drugs 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 9
• 239000004305 biphenyl Substances 0.000 claims description 9
• 235000010290 biphenyl Nutrition 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• UWMHHZFHBCYGCV-UHFFFAOYSA-N 2,3,2-tetramine Chemical compound NCCNCCCNCCN UWMHHZFHBCYGCV-UHFFFAOYSA-N 0.000 claims description 6
• SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 claims description 6
• 229910052688 Gadolinium Inorganic materials 0.000 claims description 6
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 6
• UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims description 6
• 229910052748 manganese Inorganic materials 0.000 claims description 6
• 239000011572 manganese Substances 0.000 claims description 6
• 125000004432 carbon atom Chemical group C* 0.000 claims description 5
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
• HOLGXWDGCVTMTB-UHFFFAOYSA-N 2-(2-aminophenyl)aniline Chemical group NC1=CC=CC=C1C1=CC=CC=C1N HOLGXWDGCVTMTB-UHFFFAOYSA-N 0.000 claims description 4
• 239000001294 propane Substances 0.000 claims description 4
• 150000001412 amines Chemical class 0.000 claims description 3
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 3
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
• YMJYFOZQLPXVMS-UHFFFAOYSA-N 2-[3-(2-aminoethylsulfanyl)propylsulfanyl]ethanamine Chemical compound NCCSCCCSCCN YMJYFOZQLPXVMS-UHFFFAOYSA-N 0.000 claims description 2
• 229920002521 macromolecule Polymers 0.000 claims description 2
• PCGZVYYSFSXWBO-UHFFFAOYSA-N n,n'-bis(pyridin-2-ylmethyl)propane-1,3-diamine Chemical compound C=1C=CC=NC=1CNCCCNCC1=CC=CC=N1 PCGZVYYSFSXWBO-UHFFFAOYSA-N 0.000 claims description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 11
• GFJZNBPSSAXYNH-UHFFFAOYSA-N 1,4,8,11-tetrakis(2-piperidin-2-ylethyl)-1,4,8,11-tetrazacyclotetradecane Chemical compound N1C(CCCC1)CCN1CCN(CCCN(CCN(CCC1)CCC1NCCCC1)CCC1NCCCC1)CCC1NCCCC1 GFJZNBPSSAXYNH-UHFFFAOYSA-N 0.000 claims 2
• IXDQIRNKUUFJBI-UHFFFAOYSA-N 1,4,8,11-tetrakis(3-bicyclo[3.3.1]nonanyl)-1,4,8,11-tetrazacyclotetradecane Chemical compound C1CCC(C2)CC1CC2N(CCN(CCCN(CC1)C2CC3CCCC(C3)C2)C2CC3CCCC(C3)C2)CCCN1C1CC(C2)CCCC2C1 IXDQIRNKUUFJBI-UHFFFAOYSA-N 0.000 claims 1
• ZNLXKPCIYOIWAT-UHFFFAOYSA-N 2-N-(2-dimethylphosphanylethyl)propane-1,2-diamine Chemical compound NCC(C)NCCP(C)C ZNLXKPCIYOIWAT-UHFFFAOYSA-N 0.000 claims 1
• SAQLLHDEEMZENJ-UHFFFAOYSA-N 2-amino-3-[4-(phosphonomethyl)phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=C(CP(O)(O)=O)C=C1 SAQLLHDEEMZENJ-UHFFFAOYSA-N 0.000 claims 1
• WJVAWCFQODINHM-UHFFFAOYSA-N 2-n,4-n-bis(2-aminoethyl)pentane-2,4-diamine Chemical compound NCCNC(C)CC(C)NCCN WJVAWCFQODINHM-UHFFFAOYSA-N 0.000 claims 1
• XGAWAVTYMNOWJN-UHFFFAOYSA-N 3-[3-(2-aminoethoxy)propoxy]propan-1-amine Chemical compound NCCCOCCCOCCN XGAWAVTYMNOWJN-UHFFFAOYSA-N 0.000 claims 1
• XDINHZCKMDEJDZ-UHFFFAOYSA-N n,n'-bis(2-aminoethyl)-n,n'-dimethylpropane-1,3-diamine Chemical compound NCCN(C)CCCN(C)CCN XDINHZCKMDEJDZ-UHFFFAOYSA-N 0.000 claims 1
• QMOFNAWGUJFLDN-UHFFFAOYSA-N n,n'-bis(2-piperazin-1-ylethyl)propane-1,3-diamine Chemical compound C1CNCCN1CCNCCCNCCN1CCNCC1 QMOFNAWGUJFLDN-UHFFFAOYSA-N 0.000 claims 1
• JKCHLHLFXZUVDS-UHFFFAOYSA-N n,n'-bis[2-(dimethylamino)ethyl]-n,n'-dimethylpropane-1,3-diamine Chemical compound CN(C)CCN(C)CCCN(C)CCN(C)C JKCHLHLFXZUVDS-UHFFFAOYSA-N 0.000 claims 1
• QNQYJHLKFMYGJN-UHFFFAOYSA-N nonan-3-ylcyclotetradecane Chemical compound CCCCCCC(CC)C1CCCCCCCCCCCCC1 QNQYJHLKFMYGJN-UHFFFAOYSA-N 0.000 claims 1
• 229930003799 tocopherol Natural products 0.000 claims 1
• 239000011732 tocopherol Substances 0.000 claims 1
• 235000010384 tocopherol Nutrition 0.000 claims 1
• 229960001295 tocopherol Drugs 0.000 claims 1
• 206010012601 diabetes mellitus Diseases 0.000 description 105
• 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 77
• 230000000694 effects Effects 0.000 description 66
• 241000700159 Rattus Species 0.000 description 45
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 44
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 38
• 102000004877 Insulin Human genes 0.000 description 37
• 108090001061 Insulin Proteins 0.000 description 37
• 229940125396 insulin Drugs 0.000 description 37
• 210000004556 brain Anatomy 0.000 description 33
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