HU215432B - Eljárás aldóz-reduktáz-gátló aktivitású tetrazol-ecetsav-származékok és az ezeket tartalmazó gyógyszerkészítmények előállítására - Google Patents
Eljárás aldóz-reduktáz-gátló aktivitású tetrazol-ecetsav-származékok és az ezeket tartalmazó gyógyszerkészítmények előállítására Download PDFInfo
- Publication number
- HU215432B HU215432B HU6305/90A HU630590A HU215432B HU 215432 B HU215432 B HU 215432B HU 6305/90 A HU6305/90 A HU 6305/90A HU 630590 A HU630590 A HU 630590A HU 215432 B HU215432 B HU 215432B
- Authority
- HU
- Hungary
- Prior art keywords
- tetrazol
- acetic acid
- thienyl
- methyl
- starting material
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 18
- JUNAPQMUUHSYOV-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)acetic acid Chemical class OC(=O)CC=1N=NNN=1 JUNAPQMUUHSYOV-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 11
- 230000008569 process Effects 0.000 title claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
- 102000016912 Aldehyde Reductase Human genes 0.000 title claims description 12
- 108010053754 Aldehyde reductase Proteins 0.000 title claims description 12
- -1 alkyl pentane Chemical compound 0.000 claims abstract description 138
- 150000001875 compounds Chemical class 0.000 claims abstract description 38
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 125000004494 ethyl ester group Chemical group 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- FTZVTFQXDHAIPT-UHFFFAOYSA-N 2-[5-(5-bromofuran-2-yl)tetrazol-1-yl]acetic acid Chemical compound OC(=O)CN1N=NN=C1C1=CC=C(Br)O1 FTZVTFQXDHAIPT-UHFFFAOYSA-N 0.000 claims abstract description 4
- FMFXEXGOTDXGGX-UHFFFAOYSA-N 2-[5-(furan-2-yl)tetrazol-1-yl]acetic acid Chemical compound OC(=O)CN1N=NN=C1C1=CC=CO1 FMFXEXGOTDXGGX-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims abstract description 3
- SHLYLLZMWHTCCA-UHFFFAOYSA-N 2-[5-(5-phenylsulfanylfuran-2-yl)tetrazol-1-yl]acetic acid Chemical compound OC(=O)CN1N=NN=C1C(O1)=CC=C1SC1=CC=CC=C1 SHLYLLZMWHTCCA-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000007858 starting material Substances 0.000 claims description 90
- 239000000243 solution Substances 0.000 claims description 21
- 208000002249 Diabetes Complications Diseases 0.000 claims description 9
- 206010012655 Diabetic complications Diseases 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- PGYZIQQMXCAFTQ-UHFFFAOYSA-N 2-(5-thiophen-2-yltetrazol-1-yl)acetic acid Chemical compound OC(=O)CN1N=NN=C1C1=CC=CS1 PGYZIQQMXCAFTQ-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
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- 239000008187 granular material Substances 0.000 claims description 4
- 125000001475 halogen functional group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
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- 125000005997 bromomethyl group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
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- 239000012320 chlorinating reagent Substances 0.000 claims description 2
- 229920005556 chlorobutyl Polymers 0.000 claims description 2
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 2
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- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
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- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
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- 150000002169 ethanolamines Chemical class 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- 125000006261 methyl amino sulfonyl group Chemical group [H]N(C([H])([H])[H])S(*)(=O)=O 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 239000011593 sulfur Chemical group 0.000 claims 1
- 229910052717 sulfur Chemical group 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 16
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 3
- ZISDBXVKQJALNK-UHFFFAOYSA-N 2-[5-(5-phenylfuran-2-yl)tetrazol-1-yl]acetic acid Chemical compound OC(=O)CN1N=NN=C1C1=CC=C(C=2C=CC=CC=2)O1 ZISDBXVKQJALNK-UHFFFAOYSA-N 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract description 2
- ROYZPZFDZZICLE-UHFFFAOYSA-N 1-phenylsulfanylpiperidine Chemical compound C1CCCCN1SC1=CC=CC=C1 ROYZPZFDZZICLE-UHFFFAOYSA-N 0.000 abstract 1
- 241000251468 Actinopterygii Species 0.000 abstract 1
- 239000004215 Carbon black (E152) Substances 0.000 abstract 1
- PWATWSYOIIXYMA-UHFFFAOYSA-N Pentylbenzene Chemical class CCCCCC1=CC=CC=C1 PWATWSYOIIXYMA-UHFFFAOYSA-N 0.000 abstract 1
- 150000001323 aldoses Chemical class 0.000 abstract 1
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- UMRADMNOHCGLMC-UHFFFAOYSA-N 2-[5-(2-methylthiophen-3-yl)tetrazol-1-yl]acetic acid Chemical compound S1C=CC(C=2N(N=NN=2)CC(O)=O)=C1C UMRADMNOHCGLMC-UHFFFAOYSA-N 0.000 description 1
- FGTRDCODIHFWHV-UHFFFAOYSA-N 2-[5-(2-octan-4-ylthiophen-3-yl)tetrazol-1-yl]acetic acid Chemical compound S1C=CC(C=2N(N=NN=2)CC(O)=O)=C1C(CCC)CCCC FGTRDCODIHFWHV-UHFFFAOYSA-N 0.000 description 1
- ACCZTJQCQFOGON-UHFFFAOYSA-N 2-[5-(2-phenylsulfanylthiophen-3-yl)tetrazol-1-yl]acetic acid Chemical compound OC(=O)CN1N=NN=C1C1=C(SC=2C=CC=CC=2)SC=C1 ACCZTJQCQFOGON-UHFFFAOYSA-N 0.000 description 1
- RRZTYXBPHIXHBH-UHFFFAOYSA-N 2-[5-(3-acetamidothiophen-2-yl)tetrazol-1-yl]acetic acid Chemical compound C1=CSC(C=2N(N=NN=2)CC(O)=O)=C1NC(=O)C RRZTYXBPHIXHBH-UHFFFAOYSA-N 0.000 description 1
- SXFFFCDJLOQGTI-UHFFFAOYSA-N 2-[5-(3-butoxythiophen-2-yl)tetrazol-1-yl]acetic acid Chemical compound C1=CSC(C=2N(N=NN=2)CC(O)=O)=C1OCCCC SXFFFCDJLOQGTI-UHFFFAOYSA-N 0.000 description 1
- FMVXMVURQIHVKF-UHFFFAOYSA-N 2-[5-(3-hydroxythiophen-2-yl)tetrazol-1-yl]acetic acid Chemical compound OC(=O)CN1N=NN=C1C1=C(O)C=CS1 FMVXMVURQIHVKF-UHFFFAOYSA-N 0.000 description 1
- SIGLFAFAIWJHGK-UHFFFAOYSA-N 2-[5-(3-methoxythiophen-2-yl)tetrazol-1-yl]acetic acid Chemical compound C1=CSC(C=2N(N=NN=2)CC(O)=O)=C1OC SIGLFAFAIWJHGK-UHFFFAOYSA-N 0.000 description 1
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- GVBTYMKVKKXFIB-UHFFFAOYSA-N 2-[5-(5-benzylthiophen-2-yl)tetrazol-1-yl]acetic acid Chemical compound OC(=O)CN1N=NN=C1C(S1)=CC=C1CC1=CC=CC=C1 GVBTYMKVKKXFIB-UHFFFAOYSA-N 0.000 description 1
- DQDUPHJPQFVRJH-UHFFFAOYSA-N 2-[5-(5-butylfuran-2-yl)tetrazol-1-yl]acetic acid Chemical compound O1C(CCCC)=CC=C1C1=NN=NN1CC(O)=O DQDUPHJPQFVRJH-UHFFFAOYSA-N 0.000 description 1
- PDGXAFSDXVDLRT-UHFFFAOYSA-N 2-[5-(5-butylthiophen-2-yl)tetrazol-1-yl]acetic acid Chemical compound S1C(CCCC)=CC=C1C1=NN=NN1CC(O)=O PDGXAFSDXVDLRT-UHFFFAOYSA-N 0.000 description 1
- RKIAFACSGOQKQP-UHFFFAOYSA-N 2-[5-(5-methylfuran-2-yl)tetrazol-1-yl]acetic acid Chemical compound O1C(C)=CC=C1C1=NN=NN1CC(O)=O RKIAFACSGOQKQP-UHFFFAOYSA-N 0.000 description 1
- DIQBWBWCUHENMJ-UHFFFAOYSA-N 2-[5-(5-methylsulfanylthiophen-2-yl)tetrazol-1-yl]acetic acid Chemical compound S1C(SC)=CC=C1C1=NN=NN1CC(O)=O DIQBWBWCUHENMJ-UHFFFAOYSA-N 0.000 description 1
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- BXKXGZHNCPHNLO-UHFFFAOYSA-N 2-[5-[3-(butylsulfonylamino)thiophen-2-yl]tetrazol-1-yl]acetic acid Chemical compound C1=CSC(C=2N(N=NN=2)CC(O)=O)=C1NS(=O)(=O)CCCC BXKXGZHNCPHNLO-UHFFFAOYSA-N 0.000 description 1
- LKWVQTZDRWILOP-UHFFFAOYSA-N 2-[5-[5-(3-phenylpropyl)thiophen-2-yl]tetrazol-1-yl]acetic acid Chemical compound OC(=O)CN1N=NN=C1C(S1)=CC=C1CCCC1=CC=CC=C1 LKWVQTZDRWILOP-UHFFFAOYSA-N 0.000 description 1
- VSXAZTSCGCJGQS-UHFFFAOYSA-N 2-[5-[5-(bromomethyl)thiophen-2-yl]tetrazol-1-yl]acetic acid Chemical compound OC(=O)CN1N=NN=C1C1=CC=C(CBr)S1 VSXAZTSCGCJGQS-UHFFFAOYSA-N 0.000 description 1
- QQPAJQBUVWBRRZ-UHFFFAOYSA-N 2-[5-[5-(butoxymethyl)thiophen-2-yl]tetrazol-1-yl]acetic acid Chemical compound S1C(COCCCC)=CC=C1C1=NN=NN1CC(O)=O QQPAJQBUVWBRRZ-UHFFFAOYSA-N 0.000 description 1
- TUIZQMFQRHROIK-UHFFFAOYSA-N 2-[5-[5-(diethylsulfamoyl)thiophen-2-yl]tetrazol-1-yl]acetic acid Chemical compound S1C(S(=O)(=O)N(CC)CC)=CC=C1C1=NN=NN1CC(O)=O TUIZQMFQRHROIK-UHFFFAOYSA-N 0.000 description 1
- HXEFQPAABRRYDO-UHFFFAOYSA-N 2-[5-[5-(methoxymethyl)thiophen-2-yl]tetrazol-1-yl]acetic acid Chemical compound S1C(COC)=CC=C1C1=NN=NN1CC(O)=O HXEFQPAABRRYDO-UHFFFAOYSA-N 0.000 description 1
- CJWMVJXILORZQQ-UHFFFAOYSA-N 2-[5-[5-[2-hydroxyethyl(methyl)sulfamoyl]thiophen-2-yl]tetrazol-1-yl]acetic acid Chemical compound S1C(S(=O)(=O)N(CCO)C)=CC=C1C1=NN=NN1CC(O)=O CJWMVJXILORZQQ-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 208000021921 corneal disease Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- INHCSSUBVCNVSK-UHFFFAOYSA-L lithium sulfate Inorganic materials [Li+].[Li+].[O-]S([O-])(=O)=O INHCSSUBVCNVSK-UHFFFAOYSA-L 0.000 description 1
- 150000002680 magnesium Chemical class 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- RSNDTHPJXDVYPQ-UHFFFAOYSA-N methyl 2-(furan-3-carbonylamino)acetate Chemical compound COC(=O)CNC(=O)C=1C=COC=1 RSNDTHPJXDVYPQ-UHFFFAOYSA-N 0.000 description 1
- HWNHHOAQVAZTCH-UHFFFAOYSA-N methyl 2-[5-[3-(butanoylamino)thiophen-2-yl]tetrazol-1-yl]acetate Chemical compound C1=CSC(C=2N(N=NN=2)CC(=O)OC)=C1NC(=O)CCC HWNHHOAQVAZTCH-UHFFFAOYSA-N 0.000 description 1
- DOCLPKIIOXWFKR-UHFFFAOYSA-N methyl 2-[5-[3-(butylsulfonylamino)thiophen-2-yl]tetrazol-1-yl]acetate Chemical compound C(CCC)S(=O)(=O)NC1=C(SC=C1)C1=NN=NN1CC(=O)OC DOCLPKIIOXWFKR-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 150000003109 potassium Chemical class 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- ASHGTUMKRVIOLH-UHFFFAOYSA-L potassium;sodium;hydrogen phosphate Chemical compound [Na+].[K+].OP([O-])([O-])=O ASHGTUMKRVIOLH-UHFFFAOYSA-L 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- RBTVSNLYYIMMKS-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N1CC(N)C1 RBTVSNLYYIMMKS-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9402667A HUT72435A (en) | 1989-10-03 | 1990-10-02 | Pharmaceutical compositions containing aldose-reductase-inhibiting tetrazol-acetic acid derivatives and process for producing them |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25708689 | 1989-10-03 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| HU906305D0 HU906305D0 (en) | 1991-04-29 |
| HUT59132A HUT59132A (en) | 1992-04-28 |
| HU215432B true HU215432B (hu) | 1999-04-28 |
Family
ID=17301550
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU6305/90A HU215432B (hu) | 1989-10-03 | 1990-10-02 | Eljárás aldóz-reduktáz-gátló aktivitású tetrazol-ecetsav-származékok és az ezeket tartalmazó gyógyszerkészítmények előállítására |
| HU95P/P00166P HU211166A9 (en) | 1989-10-03 | 1995-06-06 | Tetrazoleacetic acid derivatives and use for aldose reductase inhibitory activity |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU95P/P00166P HU211166A9 (en) | 1989-10-03 | 1995-06-06 | Tetrazoleacetic acid derivatives and use for aldose reductase inhibitory activity |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US5068239A (enExample) |
| EP (1) | EP0421365B1 (enExample) |
| JP (1) | JPH03204875A (enExample) |
| DE (1) | DE69030044T2 (enExample) |
| HU (2) | HU215432B (enExample) |
| RU (2) | RU2052458C1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5605795A (en) * | 1986-07-24 | 1997-02-25 | Tropix, Inc. | Assays using chemiluminescent, enzymatically cleavable substituted 1,2-dioxetanes and kits therefor |
| JPH04297474A (ja) * | 1991-03-26 | 1992-10-21 | Wakamoto Pharmaceut Co Ltd | テトラゾール酢酸誘導体 |
| GB9110636D0 (en) * | 1991-05-16 | 1991-07-03 | Glaxo Group Ltd | Chemical compounds |
| US5262433A (en) * | 1991-08-06 | 1993-11-16 | Wakamoto Pharmaceutical Co., Ltd. | Tetrazoleacetic acid derivatives and method of aldose reductase inhibition therewith |
| SK262000A3 (en) * | 1997-07-22 | 2001-01-18 | Shionogi & Co | Therapeutic or prophylactic agent for glomerulopathy |
| AU2002213048A1 (en) * | 2000-10-05 | 2002-04-15 | Smith Kline Beecham Corporation | Phosphate transport inhibitors |
| AU2015215863C1 (en) * | 2009-02-06 | 2016-10-20 | Imago Pharmaceuticals, Inc. | Inhibitors of jun n-terminal kinase |
| US8450363B2 (en) * | 2009-02-06 | 2013-05-28 | Elan Pharmaceuticals, Inc. | Inhibitors of Jun N-terminal kinase |
| AU2019249571A1 (en) * | 2018-04-06 | 2020-10-01 | Nippon Soda Co., Ltd. | (Hetero)arylsulfonamide compound and pest control agent |
| MA53085B1 (fr) * | 2018-07-05 | 2022-12-30 | Bayer Ag | Thiophènecarboxamides substitués et analogues comme agents antibactériens |
| CA3144848C (en) * | 2019-06-28 | 2023-11-21 | Pfizer Inc. | 5-(thiophen-2-yl)-1h-tetrazole derivatives as bckdk inhibitors useful for treating various diseases |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1261835A (en) * | 1984-08-20 | 1989-09-26 | Masaaki Toda | (fused) benz(thio)amides |
| GB8725260D0 (en) * | 1987-10-28 | 1987-12-02 | Lilly Industries Ltd | Organic compounds |
-
1990
- 1990-09-05 JP JP2233220A patent/JPH03204875A/ja active Granted
- 1990-09-24 US US07/588,057 patent/US5068239A/en not_active Ceased
- 1990-10-02 HU HU6305/90A patent/HU215432B/hu not_active IP Right Cessation
- 1990-10-02 RU SU904831469A patent/RU2052458C1/ru active
- 1990-10-03 DE DE69030044T patent/DE69030044T2/de not_active Expired - Fee Related
- 1990-10-03 EP EP90118900A patent/EP0421365B1/en not_active Expired - Lifetime
-
1992
- 1992-09-25 US US07/951,720 patent/USRE35321E/en not_active Expired - Lifetime
-
1994
- 1994-08-24 RU RU94031212/04A patent/RU94031212A/ru unknown
-
1995
- 1995-06-06 HU HU95P/P00166P patent/HU211166A9/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0421365B1 (en) | 1997-03-05 |
| HUT59132A (en) | 1992-04-28 |
| RU2052458C1 (ru) | 1996-01-20 |
| HU211166A9 (en) | 1995-11-28 |
| EP0421365A2 (en) | 1991-04-10 |
| US5068239A (en) | 1991-11-26 |
| DE69030044T2 (de) | 1997-10-09 |
| JPH0583551B2 (enExample) | 1993-11-26 |
| USRE35321E (en) | 1996-08-27 |
| EP0421365A3 (en) | 1992-01-02 |
| DE69030044D1 (de) | 1997-04-10 |
| RU94031212A (ru) | 1996-08-10 |
| JPH03204875A (ja) | 1991-09-06 |
| HU906305D0 (en) | 1991-04-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HMM4 | Cancellation of final prot. due to non-payment of fee |