AU767889B2 - Reversing advanced glycosylation cross-links using heterocyclic-substituted thiazolium salts - Google Patents
Reversing advanced glycosylation cross-links using heterocyclic-substituted thiazolium salts Download PDFInfo
- Publication number
- AU767889B2 AU767889B2 AU14748/00A AU1474800A AU767889B2 AU 767889 B2 AU767889 B2 AU 767889B2 AU 14748/00 A AU14748/00 A AU 14748/00A AU 1474800 A AU1474800 A AU 1474800A AU 767889 B2 AU767889 B2 AU 767889B2
- Authority
- AU
- Australia
- Prior art keywords
- oxoethyl
- group
- dimethyl
- piperidinyl
- thiazolium
- Prior art date
- 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.)
- Ceased
Links
- 150000003839 salts Chemical class 0.000 title claims description 10
- 238000006206 glycosylation reaction Methods 0.000 title description 12
- 230000013595 glycosylation Effects 0.000 title description 11
- 150000001875 compounds Chemical group 0.000 claims abstract description 66
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 38
- 239000000203 mixture Substances 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 30
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 25
- 108010005094 Advanced Glycation End Products Proteins 0.000 claims abstract description 18
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 14
- -1 hexamethyleneimino, imidazolyl Chemical group 0.000 claims description 51
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 229910052717 sulfur Chemical group 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- 239000011593 sulfur Chemical group 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 230000002411 adverse Effects 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims 5
- 230000002401 inhibitory effect Effects 0.000 claims 4
- JEHZYOQJTSWSSN-UHFFFAOYSA-N 1-(3-phenyl-1,2-oxazol-5-yl)-2-(1,3-thiazol-3-ium-3-yl)ethanone Chemical compound C=1C(C=2C=CC=CC=2)=NOC=1C(=O)C[N+]=1C=CSC=1 JEHZYOQJTSWSSN-UHFFFAOYSA-N 0.000 claims 3
- 150000002500 ions Chemical class 0.000 claims 3
- GJMFMWXBNPLVEK-UHFFFAOYSA-N 2-(4,5-dimethyl-1,3-thiazol-3-ium-3-yl)-1-(3-phenyl-1,2-oxazol-5-yl)ethanone Chemical compound CC1=C(C)SC=[N+]1CC(=O)C1=CC(C=2C=CC=CC=2)=NO1 GJMFMWXBNPLVEK-UHFFFAOYSA-N 0.000 claims 2
- KXXSZJFQJBDQIM-UHFFFAOYSA-N 2-(4,5-dimethyl-1,3-thiazol-3-ium-3-yl)-1-morpholin-4-ylethanone Chemical compound CC1=C(C)SC=[N+]1CC(=O)N1CCOCC1 KXXSZJFQJBDQIM-UHFFFAOYSA-N 0.000 claims 2
- DDTLCHVGIIPVPH-UHFFFAOYSA-N 2-(4,5-dimethyl-1,3-thiazol-3-ium-3-yl)-1-thiophen-2-ylethanone Chemical compound CC1=C(C)SC=[N+]1CC(=O)C1=CC=CS1 DDTLCHVGIIPVPH-UHFFFAOYSA-N 0.000 claims 2
- 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 claims 2
- 125000004193 piperazinyl group Chemical group 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 2
- LLFTXXTVSJOFFL-UHFFFAOYSA-N 1-(2,6-dimethylmorpholin-4-yl)-2-(4,5-dimethyl-1,3-thiazol-3-ium-3-yl)ethanone Chemical compound C1C(C)OC(C)CN1C(=O)C[N+]1=CSC(C)=C1C LLFTXXTVSJOFFL-UHFFFAOYSA-N 0.000 claims 1
- CYGNBGKNQOUSCK-UHFFFAOYSA-N 2-(4,5-dimethyl-1,3-thiazol-3-ium-3-yl)-1-(4-phenylpiperazin-1-yl)ethanone Chemical compound CC1=C(C)SC=[N+]1CC(=O)N1CCN(C=2C=CC=CC=2)CC1 CYGNBGKNQOUSCK-UHFFFAOYSA-N 0.000 claims 1
- SCXNWXMCNPKVAL-UHFFFAOYSA-N 2-(4,5-dimethyl-1,3-thiazol-3-ium-3-yl)-1-pyridin-2-ylethanone Chemical compound CC1=C(C)SC=[N+]1CC(=O)C1=CC=CC=N1 SCXNWXMCNPKVAL-UHFFFAOYSA-N 0.000 claims 1
- FLBDNKMVHLLUFD-UHFFFAOYSA-N 2-[5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium-3-yl]-1-(3-phenyl-1,2-oxazol-5-yl)ethanone Chemical compound CC1=C(CCO)SC=[N+]1CC(=O)C1=CC(C=2C=CC=CC=2)=NO1 FLBDNKMVHLLUFD-UHFFFAOYSA-N 0.000 claims 1
- CJTRNNWDXJDOMI-UHFFFAOYSA-N 2-[5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium-3-yl]-1-thiophen-2-ylethanone Chemical compound CC1=C(CCO)SC=[N+]1CC(=O)C1=CC=CS1 CJTRNNWDXJDOMI-UHFFFAOYSA-N 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- UDUZHEYUSZGXTJ-UHFFFAOYSA-O ethyl 2-[2-[[2-(4,5-dimethyl-1,3-thiazol-3-ium-3-yl)acetyl]amino]-1,3-thiazol-4-yl]acetate Chemical class CCOC(=O)CC1=CSC(NC(=O)C[N+]=2C(=C(C)SC=2)C)=N1 UDUZHEYUSZGXTJ-UHFFFAOYSA-O 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- 210000005166 vasculature Anatomy 0.000 claims 1
- 230000037303 wrinkles Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 abstract description 33
- 108090000623 proteins and genes Proteins 0.000 abstract description 33
- 230000032683 aging Effects 0.000 abstract description 23
- 238000004132 cross linking Methods 0.000 abstract description 14
- 230000001225 therapeutic effect Effects 0.000 abstract description 6
- 235000013305 food Nutrition 0.000 abstract description 4
- 235000018102 proteins Nutrition 0.000 abstract 2
- 235000021120 animal protein Nutrition 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 210000003743 erythrocyte Anatomy 0.000 description 11
- 230000002441 reversible effect Effects 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 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 9
- 239000008103 glucose Substances 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- 102000008186 Collagen Human genes 0.000 description 8
- 108010035532 Collagen Proteins 0.000 description 8
- 229920001436 collagen Polymers 0.000 description 8
- 108010055267 advanced glycation end products-bovine serum albumin Proteins 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 229920000136 polysorbate Polymers 0.000 description 7
- WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical compound CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 6
- 239000000872 buffer Substances 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 150000004820 halides Chemical group 0.000 description 5
- 229940027941 immunoglobulin g Drugs 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- UHWNENCHFSDZQP-UHFFFAOYSA-N 2-bromo-1-thiophen-2-ylethanone Chemical compound BrCC(=O)C1=CC=CS1 UHWNENCHFSDZQP-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000036252 glycation Effects 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- AAOSLLBWWRKJIR-UHFFFAOYSA-N 2-chloro-1-pyrrolidin-1-ylethanone Chemical compound ClCC(=O)N1CCCC1 AAOSLLBWWRKJIR-UHFFFAOYSA-N 0.000 description 3
- UWSONZCNXUSTKW-UHFFFAOYSA-N 4,5-Dimethylthiazole Chemical compound CC=1N=CSC=1C UWSONZCNXUSTKW-UHFFFAOYSA-N 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 3
- 102000014824 Crystallins Human genes 0.000 description 3
- 108010064003 Crystallins Proteins 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000008092 positive effect Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- DDGHBOLOCQWPKE-UHFFFAOYSA-N 1,3-thiazole;hydrobromide Chemical compound [Br-].C1=CSC=[NH+]1 DDGHBOLOCQWPKE-UHFFFAOYSA-N 0.000 description 2
- TZXYREZVXALUJX-UHFFFAOYSA-M 1-(3-phenyl-1,2-oxazol-5-yl)-2-(1,3-thiazol-3-ium-3-yl)ethanone;bromide Chemical compound [Br-].C=1C(C=2C=CC=CC=2)=NOC=1C(=O)C[N+]=1C=CSC=1 TZXYREZVXALUJX-UHFFFAOYSA-M 0.000 description 2
- OBSLLHNATPQFMJ-UHFFFAOYSA-N 2,4-Dimethylthiazole Chemical compound CC1=CSC(C)=N1 OBSLLHNATPQFMJ-UHFFFAOYSA-N 0.000 description 2
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000016942 Elastin Human genes 0.000 description 2
- 108010014258 Elastin Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 239000001058 brown pigment Substances 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229920002549 elastin Polymers 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 238000010874 in vitro model Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 125000006384 methylpyridyl group Chemical group 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 230000036581 peripheral resistance Effects 0.000 description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- SPYGDICNRQMZMX-UHFFFAOYSA-M 1-(4-benzylpiperazin-1-yl)-2-(4,5-dimethyl-1,3-thiazol-3-ium-3-yl)ethanone;chloride Chemical compound [Cl-].CC1=C(C)SC=[N+]1CC(=O)N1CCN(CC=2C=CC=CC=2)CC1 SPYGDICNRQMZMX-UHFFFAOYSA-M 0.000 description 1
- PDZIOKIBWAJQNY-UHFFFAOYSA-M 1-(4-benzylpiperazin-1-yl)-2-(4-octyl-1,3-thiazol-3-ium-3-yl)ethanone;chloride Chemical compound [Cl-].CCCCCCCCC1=CSC=[N+]1CC(=O)N1CCN(CC=2C=CC=CC=2)CC1 PDZIOKIBWAJQNY-UHFFFAOYSA-M 0.000 description 1
- LXFQSRIDYRFTJW-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonic acid Chemical class CC1=CC(C)=C(S(O)(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-N 0.000 description 1
- KWCRMLXZLWVARI-UHFFFAOYSA-M 2-(4,5-dimethyl-1,3-thiazol-3-ium-3-yl)-1-thiophen-2-ylethanone;bromide Chemical compound [Br-].CC1=C(C)SC=[N+]1CC(=O)C1=CC=CS1 KWCRMLXZLWVARI-UHFFFAOYSA-M 0.000 description 1
- QHQQHTYVQOPPPR-UHFFFAOYSA-M 2-[5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium-3-yl]-1-(3-phenyl-1,2-oxazol-5-yl)ethanone;bromide Chemical compound [Br-].CC1=C(CCO)SC=[N+]1CC(=O)C1=CC(C=2C=CC=CC=2)=NO1 QHQQHTYVQOPPPR-UHFFFAOYSA-M 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- IJBVSJKBNSQVAX-UHFFFAOYSA-N 4,5-dimethyl-1,3-thiazol-3-ium;chloride Chemical compound [Cl-].CC=1[NH+]=CSC=1C IJBVSJKBNSQVAX-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- 208000000575 Arteriosclerosis Obliterans Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 208000005156 Dehydration Diseases 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 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
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000002704 decyl 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])* 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000036576 dermal application Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000012153 distilled water Substances 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
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 210000000585 glomerular basement membrane Anatomy 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 238000012332 laboratory investigation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000008935 nutritious Nutrition 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008756 pathogenetic mechanism Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 231100000255 pathogenic effect Toxicity 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007909 solid dosage form Substances 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
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 150000007979 thiazole derivatives Chemical class 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Catalysts (AREA)
- Cosmetics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/189,200 US6121300A (en) | 1998-11-10 | 1998-11-10 | Reversing advanced glycosylation cross-links using heterocyclic-substituted thiazolium salts |
| US09/189200 | 1998-11-10 | ||
| PCT/US1999/026565 WO2000027395A1 (en) | 1998-11-10 | 1999-11-10 | Reversing advanced glycosylation cross-links using heterocyclic-substituted thiazolium salts |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1474800A AU1474800A (en) | 2000-05-29 |
| AU767889B2 true AU767889B2 (en) | 2003-11-27 |
Family
ID=22696355
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU14748/00A Ceased AU767889B2 (en) | 1998-11-10 | 1999-11-10 | Reversing advanced glycosylation cross-links using heterocyclic-substituted thiazolium salts |
Country Status (11)
| Country | Link |
|---|---|
| US (4) | US6121300A (enExample) |
| EP (1) | EP1128830B1 (enExample) |
| JP (1) | JP2002529414A (enExample) |
| KR (1) | KR20010080969A (enExample) |
| AT (1) | ATE388704T1 (enExample) |
| AU (1) | AU767889B2 (enExample) |
| CA (1) | CA2350211A1 (enExample) |
| DE (1) | DE69938357D1 (enExample) |
| MX (1) | MXPA01004721A (enExample) |
| NZ (1) | NZ511569A (enExample) |
| WO (1) | WO2000027395A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5656261A (en) | 1995-01-18 | 1997-08-12 | The Picower Institute For Medical Research | Preventing and reversing advanced glycosylation endproducts |
| NO315930B1 (no) * | 1995-01-18 | 2003-11-17 | Picower Inst For Medical Res T | Anvendelse av tiazoliumforbindelser ved fremstilling av farmasöytiske preparater, preparater som inneholder forbindelsene, samt nyetiazoliumforbindelser |
| US6121300A (en) * | 1998-11-10 | 2000-09-19 | Wagle; Dilip R. | Reversing advanced glycosylation cross-links using heterocyclic-substituted thiazolium salts |
| US6458819B1 (en) * | 2000-02-23 | 2002-10-01 | Alteon, Inc. | Thiazolium compounds and treatments of disorders associated with protein aging |
| ATE304849T1 (de) * | 2000-07-13 | 2005-10-15 | Alteon Inc | Cyanomethyl-substituierte thiazolium- und imidazolium-verbindungen und behandlung von erkrankungen im zusammenhang mit proteinalterung |
| WO2002018355A1 (en) * | 2000-08-23 | 2002-03-07 | Eli Lilly And Company | Oxazolyl-aryloxyacetic acid derivatives and their use as ppar agonists |
| CA2433425A1 (en) * | 2000-12-29 | 2002-09-06 | Alteon, Inc. | Method for treating fibrotic diseases or other indications iiic |
| EP1353676A4 (en) * | 2000-12-29 | 2006-05-31 | Alteon Inc | METHOD FOR THE TREATMENT OF FIBROUS OR OTHER INDICATIONS |
| AU2002232919A1 (en) * | 2000-12-29 | 2002-07-16 | Alteon, Inc. | Method for treating fibrotic diseases or other indications |
| WO2002053158A1 (en) * | 2000-12-29 | 2002-07-11 | Alteon, Inc. | Method for treating glaucoma ib |
| WO2002056836A2 (en) * | 2001-01-22 | 2002-07-25 | Farrington Pharmaceuticals, Llc | Method and composition for rejuvenating hair, nails, tissues, cells and organs by ex-vivo or immersive treatment |
| US7022721B1 (en) * | 2001-02-07 | 2006-04-04 | Peter C Ulrich | Method and composition for rejuvenating cells, tissues, organs, hair and nails |
| EP1404339A4 (en) * | 2001-05-30 | 2004-08-25 | Alteon Inc | METHOD FOR TREATING FIBROTIC DISEASES OR OTHER INDICATIONS VI |
| CN1324019C (zh) * | 2003-04-02 | 2007-07-04 | 深圳市东阳光实业发展有限公司 | 氮杂双环盐类化合物及其治疗蛋白老化疾病的用途 |
| US20050014747A1 (en) * | 2003-04-18 | 2005-01-20 | Emily Reinhard | Dihydrothiazine prodrugs of thiazolium agents |
| US20040265238A1 (en) | 2003-06-27 | 2004-12-30 | Imtiaz Chaudry | Inhalable formulations for treating pulmonary hypertension and methods of using same |
| AU2005214971A1 (en) * | 2004-02-17 | 2005-09-01 | Dynamis Therapeutics, Inc. | Fructoseamine 3 kinase and the formation of collagen and elastin |
| CN1690057B (zh) * | 2004-04-21 | 2010-05-26 | 北京摩力克科技有限公司 | 硒吩类衍生物及其预防和/或者治疗蛋白老化相关疾病的用途 |
| CN100560589C (zh) * | 2004-04-21 | 2009-11-18 | 北京摩力克科技有限公司 | 咪唑并硒唑类化合物及其预防和/或者治疗与蛋白老化相关疾病的用途 |
| WO2006032165A1 (en) * | 2004-09-23 | 2006-03-30 | Beijing Molecule Science And Technology Co., Ltd | Novel substituted 5-membered-n-heterocyclic compounds and the use of them in treatment of the diseases associated with the aging of proteins |
| JP5345399B2 (ja) * | 2006-01-23 | 2013-11-20 | ザ プロクター アンド ギャンブル カンパニー | チアゾリウム染料を有する洗濯ケア組成物 |
| CN101007789B (zh) | 2006-01-27 | 2014-08-20 | 北京摩力克科技有限公司 | 取代五元氮杂环盐类化合物及其治疗蛋白老化相关疾病的用途 |
| FR2918570B1 (fr) * | 2007-07-09 | 2012-10-05 | Engelhard Lyon | DIGLYCATION DES AGEs. |
| WO2009123753A1 (en) | 2008-04-04 | 2009-10-08 | North Carolina State University | Inhibition of bacterial biofilms with imidazole-phenyl derivatives |
| US9221765B2 (en) | 2009-06-10 | 2015-12-29 | North Carolina State University | Inhibition and dispersion of bacterial biofilms with benzimidazole derivatives |
| US9796952B2 (en) | 2012-09-25 | 2017-10-24 | The Procter & Gamble Company | Laundry care compositions with thiazolium dye |
| WO2016179089A1 (en) | 2015-05-01 | 2016-11-10 | Rensselaer Polytechnic Institute | Biomimetic nano-composite scaffold for enhanced bone healing and fracture repair |
| CN109431850A (zh) * | 2018-03-16 | 2019-03-08 | 广东众尔健生物科技有限公司 | 一种鼠尾胶原在化妆品领域的应用 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5857116A (ja) * | 1981-09-30 | 1983-04-05 | Konishiroku Photo Ind Co Ltd | マイクロプロセツサを塔載したカメラ |
| GB8300728D0 (en) * | 1983-01-12 | 1983-02-16 | Erba Farmitalia | Substituted carboxy-thiazolo / 3 2 - a / pyrimidine derivatives |
| JPS60184038A (ja) * | 1984-03-01 | 1985-09-19 | Nippon Kasei Kk | １−ヒドロキシ−２−オン類の製造方法 |
| CA1273011A (en) * | 1984-07-02 | 1990-08-21 | Susan M. Schmitt | Carbapenems having an externally alkylated mono- or bicyclic 2-quaternary heteroarylalkylthio substituent |
| CA1273012A (en) * | 1984-07-02 | 1990-08-21 | Burton G. Christensen | 1-methylcarbapenems having an externally alkylated mono- of bicyclic 2-quarternary heteroarylalkylthio substituent |
| US4609670A (en) * | 1984-11-13 | 1986-09-02 | Eli Lilly And Company | Imidazolium hypoglycemic agents |
| US4683312A (en) * | 1984-11-13 | 1987-07-28 | Eli Lilly And Company | Imidazolium hypoglycemic agents |
| ZA86171B (en) | 1985-01-16 | 1986-08-27 | Hoffmann La Roche | Polycyclic salts |
| US4886814A (en) * | 1986-03-13 | 1989-12-12 | Dr. Karl Thomas Gmbh | Substituted thiazoles and oxazoles and 2-hydroxy-morpholines |
| DE3621775A1 (de) * | 1986-03-13 | 1988-01-07 | Thomae Gmbh Dr K | Neue substituierte thiazole und oxazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| US5219852A (en) * | 1986-03-13 | 1993-06-15 | Dr. Karl Thomae Gmbh | Substituted thiazoles and oxazoles and pharmaceutical compositions and methods thereof |
| US5185334A (en) * | 1989-07-31 | 1993-02-09 | Schering Corporation | 2,2-disubstituted glycerol and glycerol-like compounds, compositions and methods of use |
| JP2817219B2 (ja) * | 1988-09-08 | 1998-10-30 | 武田薬品工業株式会社 | カルバジン酸誘導体、その製造法及び製剤 |
| DE3839758A1 (de) * | 1988-10-24 | 1990-04-26 | Bayer Ag | Substituierte 2-aminothiazole |
| US5302608A (en) * | 1988-11-18 | 1994-04-12 | Takeda Chemical Industries, Ltd. | Age formation inhibitors |
| US5128351A (en) * | 1990-05-04 | 1992-07-07 | American Cyanamid Company | Bis-aryl amide and urea antagonists of platelet activating factor |
| US5225425A (en) * | 1990-05-04 | 1993-07-06 | American Cyanamid Company | Bis-aryl amide antagonists of platelet activating factor |
| DE4124587A1 (de) * | 1991-07-24 | 1993-01-28 | Luitpold Werk Chem Pharm | Dimethylacetessigsaeureamide, verfahren zu ihrer herstellung und arzneimittel |
| US5230998A (en) * | 1991-07-25 | 1993-07-27 | Neurath Alexander R | Method for the prescreening of drugs targeted to the V3 hypervariable loop of the HIV-1 envelope glycoprotein gp 120 |
| DE4129742A1 (de) * | 1991-09-06 | 1993-03-11 | Bayer Ag | Heterocyclisch substituierte chinolylmethoxy-phenylacetamide |
| DE4218159C2 (de) * | 1992-06-02 | 1997-07-31 | Luitpold Pharma Gmbh | 4,4,4-Trifluoracetessigsäureamide, Verfahren zu ihrer Herstellung und Arzneimittel |
| DE4222980A1 (de) * | 1992-07-13 | 1994-01-20 | Cassella Ag | Verwendung von 2-(N-(2-Aminoethyl)amino)-essigsäure-derivaten |
| ES2096933T3 (es) * | 1992-07-30 | 1997-03-16 | Drug Delivery System Inst Ltd | Compuesto capaz de permanecer en la region intracerebral y utilizacion del mismo. |
| TW268952B (enExample) * | 1993-02-26 | 1996-01-21 | Takeda Pharm Industry Co Ltd | |
| JP3126541B2 (ja) * | 1993-03-26 | 2001-01-22 | 千寿製薬株式会社 | ベンゾチアゾール誘導体、その製法及びその用途 |
| DE4341526A1 (de) * | 1993-12-06 | 1995-06-08 | Basf Ag | 2,4-Diaminothiazole und ihre Herstellung |
| US5700819A (en) * | 1994-11-29 | 1997-12-23 | Grelan Pharmaceutical Co., Ltd. | 2-substituted benzothiazole derivatives and prophylactic and therapeutic agents for the treatment of diabetic complications |
| US5656261A (en) * | 1995-01-18 | 1997-08-12 | The Picower Institute For Medical Research | Preventing and reversing advanced glycosylation endproducts |
| US5853703A (en) * | 1995-01-18 | 1998-12-29 | The Picower Institute For Medical Research | Preventing and reversing the formation of advanced glycosylation endproducts |
| US5744451A (en) * | 1995-09-12 | 1998-04-28 | Warner-Lambert Company | N-substituted glutamic acid derivatives with interleukin-1 β converting enzyme inhibitory activity |
| US6121300A (en) * | 1998-11-10 | 2000-09-19 | Wagle; Dilip R. | Reversing advanced glycosylation cross-links using heterocyclic-substituted thiazolium salts |
-
1998
- 1998-11-10 US US09/189,200 patent/US6121300A/en not_active Expired - Fee Related
-
1999
- 1999-11-10 CA CA002350211A patent/CA2350211A1/en not_active Abandoned
- 1999-11-10 AT AT99971712T patent/ATE388704T1/de not_active IP Right Cessation
- 1999-11-10 EP EP99971712A patent/EP1128830B1/en not_active Expired - Lifetime
- 1999-11-10 KR KR1020017005846A patent/KR20010080969A/ko not_active Ceased
- 1999-11-10 AU AU14748/00A patent/AU767889B2/en not_active Ceased
- 1999-11-10 WO PCT/US1999/026565 patent/WO2000027395A1/en not_active Ceased
- 1999-11-10 MX MXPA01004721A patent/MXPA01004721A/es unknown
- 1999-11-10 JP JP2000580624A patent/JP2002529414A/ja active Pending
- 1999-11-10 DE DE69938357T patent/DE69938357D1/de not_active Expired - Lifetime
- 1999-11-10 NZ NZ511569A patent/NZ511569A/xx unknown
-
2000
- 2000-08-23 US US09/644,024 patent/US6319934B1/en not_active Expired - Fee Related
-
2001
- 2001-10-23 US US10/003,514 patent/US20020160992A1/en not_active Abandoned
-
2003
- 2003-01-21 US US10/348,378 patent/US6790859B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20020160992A1 (en) | 2002-10-31 |
| CA2350211A1 (en) | 2000-05-18 |
| DE69938357D1 (de) | 2008-04-24 |
| NZ511569A (en) | 2003-06-30 |
| US20030176417A1 (en) | 2003-09-18 |
| EP1128830A4 (en) | 2004-03-31 |
| EP1128830B1 (en) | 2008-03-12 |
| AU1474800A (en) | 2000-05-29 |
| MXPA01004721A (es) | 2002-09-18 |
| US6121300A (en) | 2000-09-19 |
| US6319934B1 (en) | 2001-11-20 |
| ATE388704T1 (de) | 2008-03-15 |
| WO2000027395A1 (en) | 2000-05-18 |
| EP1128830A1 (en) | 2001-09-05 |
| KR20010080969A (ko) | 2001-08-25 |
| US6790859B2 (en) | 2004-09-14 |
| JP2002529414A (ja) | 2002-09-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU767889B2 (en) | Reversing advanced glycosylation cross-links using heterocyclic-substituted thiazolium salts | |
| JP2002529414A5 (enExample) | ||
| USRE38330E1 (en) | Preventing and reversing advanced glycosylation endproducts | |
| AU622419B2 (en) | Inhibitors of non-enzymatic cross-linking | |
| AU782500B2 (en) | Thiazole, imidazole and oxazole compounds and treatments of disorders associated with protein aging | |
| US20070249519A1 (en) | Methods for the upregulation of glut4 via modulation of ppar delta in adipose tissue and for the treatment of disease | |
| US20020177586A1 (en) | Method for treating fibrotic diseases or other indications ID | |
| US5358960A (en) | Method for inhibiting advanced glycosylation of proteins using aminosubstituted imidazoles | |
| EP1353676A1 (en) | Method for treating fibrotic diseases or other indications | |
| JP2010248205A (ja) | 強皮症の治療のためのベンザゾール誘導体 | |
| EP0327919B1 (en) | Method and agents for preventing staining of teeth | |
| US6458819B1 (en) | Thiazolium compounds and treatments of disorders associated with protein aging | |
| US20070190079A1 (en) | Methods for the selective modulation of ppar | |
| EP1353669B1 (en) | Method for treating glaucoma | |
| US5661139A (en) | Bis-(2-aryl) hydrazones | |
| WO1996040663A1 (en) | Di- and tri-aminoguanidines and their use to inhibit the advanced glycosylation of proteins | |
| US6060470A (en) | Triazine compounds and methods of use therefor | |
| JP2006504627A (ja) | 化合物および方法 | |
| AU727846B2 (en) | 1,2,4-triazine derivatives for the inhibition of protein glycosylation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |