JP3581103B2 - ソルビトールデヒドロゲナーゼ阻害薬としてのアミノピリミジン - Google Patents
ソルビトールデヒドロゲナーゼ阻害薬としてのアミノピリミジン Download PDFInfo
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- JP3581103B2 JP3581103B2 JP2000609073A JP2000609073A JP3581103B2 JP 3581103 B2 JP3581103 B2 JP 3581103B2 JP 2000609073 A JP2000609073 A JP 2000609073A JP 2000609073 A JP2000609073 A JP 2000609073A JP 3581103 B2 JP3581103 B2 JP 3581103B2
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- JP
- Japan
- Prior art keywords
- pyrimidin
- alkyl
- dimethyl
- piperazin
- hydroxy
- 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.)
- Expired - Fee Related
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- 239000003112 inhibitor Substances 0.000 title description 50
- 108010009384 L-Iditol 2-Dehydrogenase Proteins 0.000 title description 12
- 102100026974 Sorbitol dehydrogenase Human genes 0.000 title description 12
- 150000005005 aminopyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 640
- -1 2- (4-methylpiperazin-1-yl) -pyrimid-4-yl Chemical group 0.000 claims description 528
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 385
- 125000000217 alkyl group Chemical group 0.000 claims description 228
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 217
- 238000006243 chemical reaction Methods 0.000 claims description 174
- 229910052739 hydrogen Inorganic materials 0.000 claims description 168
- 239000001257 hydrogen Substances 0.000 claims description 167
- 150000003839 salts Chemical class 0.000 claims description 164
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 143
- 238000000034 method Methods 0.000 claims description 120
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 99
- 239000012442 inert solvent Substances 0.000 claims description 54
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 51
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 48
- 125000002757 morpholinyl group Chemical group 0.000 claims description 40
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 38
- 125000005466 alkylenyl group Chemical group 0.000 claims description 37
- 125000004193 piperazinyl group Chemical group 0.000 claims description 35
- 125000002883 imidazolyl group Chemical group 0.000 claims description 24
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 21
- 125000001425 triazolyl group Chemical group 0.000 claims description 15
- 125000004306 triazinyl group Chemical group 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- AEOZCEMLLBCHQZ-HSHFZTNMSA-N (2r)-2-hydroxypropanimidamide;hydrochloride Chemical compound Cl.C[C@@H](O)C(N)=N AEOZCEMLLBCHQZ-HSHFZTNMSA-N 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims description 4
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 claims description 3
- 125000006242 amine protecting group Chemical group 0.000 claims description 3
- SXQFCVDSOLSHOQ-UWTATZPHSA-N (R)-(+)-Lactamide Chemical compound C[C@@H](O)C(N)=O SXQFCVDSOLSHOQ-UWTATZPHSA-N 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 6
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
- 239000000651 prodrug Substances 0.000 description 279
- 229940002612 prodrug Drugs 0.000 description 279
- 125000001153 fluoro group Chemical group F* 0.000 description 256
- 125000003545 alkoxy group Chemical group 0.000 description 135
- 125000005843 halogen group Chemical group 0.000 description 89
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 86
- 239000002904 solvent Substances 0.000 description 80
- 125000001424 substituent group Chemical group 0.000 description 61
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 56
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
- 241000124008 Mammalia Species 0.000 description 48
- 229910052757 nitrogen Chemical group 0.000 description 47
- 125000004076 pyridyl group Chemical group 0.000 description 47
- 102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 description 45
- 108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 description 45
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 150000001412 amines Chemical class 0.000 description 41
- 239000002585 base Substances 0.000 description 39
- 125000002785 azepinyl group Chemical group 0.000 description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 33
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 33
- 239000003288 aldose reductase inhibitor Substances 0.000 description 32
- 210000002216 heart Anatomy 0.000 description 32
- 125000003386 piperidinyl group Chemical group 0.000 description 32
- 230000035484 reaction time Effects 0.000 description 32
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 31
- 208000002249 Diabetes Complications Diseases 0.000 description 30
- 206010012655 Diabetic complications Diseases 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- 125000006239 protecting group Chemical group 0.000 description 30
- 238000010992 reflux Methods 0.000 description 30
- 229920006395 saturated elastomer Polymers 0.000 description 30
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 29
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 29
- 229960004198 guanidine Drugs 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 206010012601 diabetes mellitus Diseases 0.000 description 27
- 125000002971 oxazolyl group Chemical group 0.000 description 27
- 125000000335 thiazolyl group Chemical group 0.000 description 27
- 210000001519 tissue Anatomy 0.000 description 27
- 102100022897 Sodium/hydrogen exchanger 10 Human genes 0.000 description 26
- 125000002947 alkylene group Chemical group 0.000 description 26
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 25
- 150000002431 hydrogen Chemical class 0.000 description 25
- 230000000302 ischemic effect Effects 0.000 description 25
- 125000001544 thienyl group Chemical group 0.000 description 25
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 24
- 125000002541 furyl group Chemical group 0.000 description 24
- 150000008282 halocarbons Chemical class 0.000 description 24
- 229910052760 oxygen Inorganic materials 0.000 description 24
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 23
- ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 229940118148 Aldose reductase inhibitor Drugs 0.000 description 22
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 22
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
- 229910052717 sulfur Inorganic materials 0.000 description 21
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 20
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 20
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 18
- 125000002393 azetidinyl group Chemical group 0.000 description 18
- 239000003153 chemical reaction reagent Substances 0.000 description 18
- 150000002170 ethers Chemical class 0.000 description 18
- 239000001301 oxygen Substances 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 239000000600 sorbitol Substances 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 208000028867 ischemia Diseases 0.000 description 17
- 238000011282 treatment Methods 0.000 description 17
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 16
- 239000003054 catalyst Substances 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- 239000011593 sulfur Chemical group 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 125000005090 alkenylcarbonyl group Chemical group 0.000 description 14
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 14
- 229910052799 carbon Inorganic materials 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 14
- 230000002107 myocardial effect Effects 0.000 description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 description 14
- 239000003880 polar aprotic solvent Substances 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 14
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 239000007822 coupling agent Substances 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 125000001624 naphthyl group Chemical group 0.000 description 13
- 238000006722 reduction reaction Methods 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 125000002619 bicyclic group Chemical group 0.000 description 12
- 230000005961 cardioprotection Effects 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 12
- 125000002098 pyridazinyl group Chemical group 0.000 description 12
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 12
- 230000010410 reperfusion Effects 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 11
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- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 11
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- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
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- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 9
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- 150000007529 inorganic bases Chemical class 0.000 description 9
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- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical group CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
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- 125000004414 alkyl thio group Chemical group 0.000 description 8
- 210000004351 coronary vessel Anatomy 0.000 description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 8
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- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
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- YUSMZDVTEOAHDL-UHFFFAOYSA-N tert-butyl 3-(dimethylaminomethylidene)-4-oxopiperidine-1-carboxylate Chemical compound CN(C)C=C1CN(C(=O)OC(C)(C)C)CCC1=O YUSMZDVTEOAHDL-UHFFFAOYSA-N 0.000 description 1
- UIYOVVYZPVVUMJ-UHFFFAOYSA-N tert-butyl carbamoyl carbonate Chemical compound CC(C)(C)OC(=O)OC(N)=O UIYOVVYZPVVUMJ-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
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- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
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- 125000006168 tricyclic group Chemical group 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
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- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
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| US12743799P | 1999-04-01 | 1999-04-01 | |
| US60/127,437 | 1999-04-01 | ||
| PCT/IB2000/000296 WO2000059510A1 (en) | 1999-04-01 | 2000-03-16 | Aminopyrimidines as sorbitol dehydrogenase inhibitors |
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| JP2002541109A JP2002541109A (ja) | 2002-12-03 |
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| JP2004517053A (ja) * | 2000-10-18 | 2004-06-10 | ファイザー・プロダクツ・インク | スタチン類とソルビトールデヒドロゲナーゼ阻害薬の併用 |
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| KR20180095564A (ko) * | 2015-12-22 | 2018-08-27 | 지앙수 헨그루이 메디슨 컴퍼니 리미티드 | 벤조피페리딘 유도체, 이의 제조 방법 및 이의 의학적 용도 |
| US9988367B2 (en) | 2016-05-03 | 2018-06-05 | Bayer Pharma Aktiengesellschaft | Amide-substituted pyridinyltriazole derivatives and uses thereof |
| CN109071464A (zh) | 2016-05-03 | 2018-12-21 | 拜耳制药股份公司 | 氧代烷基取代的苯基三唑衍生物及其用途 |
| US11083720B2 (en) | 2017-03-17 | 2021-08-10 | Regents Of The University Of Colorado, A Body Corporate | Indazole inhibitors of fructokinase (KHK) and methods of use in treating KHK-mediated disorders or diseases |
| IL272246B1 (en) | 2017-07-28 | 2025-09-01 | Applied Therapeutics Inc | Derivatives of 2-(4-oxo/thioketone/azo-3-((substituted)benzo[d]thiazol-2-yl)methyl)- 3,4-dihydrothieno[3,4-d]pyridazin-1-yl)acetic acid for use as aldose reductase inhibitors in treating galactosemia or preventing complications associated with galactosemia |
| CN110872302B (zh) * | 2018-08-31 | 2022-09-27 | 沈阳中化农药化工研发有限公司 | 含嘧啶的螺环类化合物及其用途 |
| MX2021013511A (es) * | 2019-05-07 | 2022-02-23 | Univ Miami | Tratamiento y deteccion de neuropatias heredadas y trastornos asociados. |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3905364A1 (de) * | 1989-02-22 | 1990-08-23 | Hoechst Ag | Substituierte pyrimidin-derivate, verfahren zu ihrer herstellung und ihre verwendung als tool |
| DE4025387A1 (de) * | 1990-08-10 | 1992-02-13 | Hoechst Ag | Substituierte pyrimidin-derivate, verfahren zu ihrer herstellung und ihre verwendung als reagenzien |
| NZ254550A (en) * | 1992-09-28 | 1997-08-22 | Pfizer | Use of nitrogen-substituted pyrimidines to prepare medicaments useful for treatment or prevention of diabetic complications |
| DK0791355T3 (da) * | 1996-02-29 | 2002-06-17 | Pfizer | Fremgangsmåde til reduktion af vævsbeskadigelse forbundet med iskæmi |
| IT1285601B1 (it) | 1996-03-08 | 1998-06-18 | Bonfiglioli Riduttori Spa | Riduttore angolare a piu' stadi |
| EA004656B1 (ru) * | 1999-04-01 | 2004-06-24 | Пфайзер Продактс Инк. | Аминопиримидины в качестве ингибиторов сорбитолдегидрогеназы |
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