IL98300A - Oxa- and thiazolidinedione hypoglycemic and hypocholesterolemic compounds and pharmaceutical preparations containing them - Google Patents

Oxa- and thiazolidinedione hypoglycemic and hypocholesterolemic compounds and pharmaceutical preparations containing them

Info

Publication number: IL98300A
Authority: IL; Israel
Prior art keywords: compound; compounds; formula; hypoglycemic; hydrogen
Prior art date: 1990-06-05

Application number

IL9830091A

Other languages

English (en)

Other versions

IL98300A0 (en

Original Assignee

Pfizer

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

1990-06-05

Filing date

1991-05-29

Publication date

1996-01-31

1991-05-29 Application filed by Pfizer filed Critical Pfizer

1992-06-21 Publication of IL98300A0 publication Critical patent/IL98300A0/xx

1996-01-31 Publication of IL98300A publication Critical patent/IL98300A/en

Links

150000001875 compounds Chemical class 0.000 title claims description 55
230000002218 hypoglycaemic effect Effects 0.000 title description 12
ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 title description 5
229940123464 Thiazolidinedione Drugs 0.000 title description 5
COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 title description 3
230000000871 hypocholesterolemic effect Effects 0.000 title description 2
239000000825 pharmaceutical preparation Substances 0.000 title description 2
238000002360 preparation method Methods 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 16
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 14
210000004369 blood Anatomy 0.000 claims description 12
239000008280 blood Substances 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
241000124008 Mammalia Species 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
230000000260 hypercholesteremic effect Effects 0.000 claims description 3
230000003345 hyperglycaemic effect Effects 0.000 claims description 3
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000002541 furyl group Chemical group 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
125000001424 substituent group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
230000010030 glucose lowering effect Effects 0.000 claims 1
239000003472 antidiabetic agent Substances 0.000 abstract description 9
229940125708 antidiabetic agent Drugs 0.000 abstract description 3
239000003529 anticholesteremic agent Substances 0.000 abstract description 2
150000001477 2,4-oxazolidinediones Chemical class 0.000 abstract 1
150000001473 2,4-thiazolidinediones Chemical class 0.000 abstract 1
230000003178 anti-diabetic effect Effects 0.000 abstract 1
229940127226 anticholesterol agent Drugs 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
238000000034 method Methods 0.000 description 19
239000000243 solution Substances 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 15
239000000047 product Substances 0.000 description 15
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
239000003054 catalyst Substances 0.000 description 11
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 10
241001465754 Metazoa Species 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000008103 glucose Substances 0.000 description 10
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
239000007787 solid Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
-1 R1 and R^ include Rg Substances 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
230000000694 effects Effects 0.000 description 7
238000005984 hydrogenation reaction Methods 0.000 description 7
238000006467 substitution reaction Methods 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
239000000725 suspension Substances 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
102000004877 Insulin Human genes 0.000 description 5
108090001061 Insulin Proteins 0.000 description 5
239000002585 base Substances 0.000 description 5
238000010828 elution Methods 0.000 description 5
229940126904 hypoglycaemic agent Drugs 0.000 description 5
229940125396 insulin Drugs 0.000 description 5
229910052717 sulfur Inorganic materials 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
229940079593 drug Drugs 0.000 description 4
229910000510 noble metal Inorganic materials 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
239000011593 sulfur Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
244000309464 bull Species 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000011097 chromatography purification Methods 0.000 description 3
206010012601 diabetes mellitus Diseases 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
150000002431 hydrogen Chemical class 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
239000013641 positive control Substances 0.000 description 3
229910052703 rhodium Inorganic materials 0.000 description 3
239000010948 rhodium Substances 0.000 description 3
150000001467 thiazolidinediones Chemical class 0.000 description 3
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 2
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 description 2
108010007622 LDL Lipoproteins Proteins 0.000 description 2
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229940100389 Sulfonylurea Drugs 0.000 description 2
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
108010069201 VLDL Cholesterol Proteins 0.000 description 2
230000005856 abnormality Effects 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
230000037396 body weight Effects 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
125000002091 cationic group Chemical group 0.000 description 2
235000012000 cholesterol Nutrition 0.000 description 2
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
229960001231 choline Drugs 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
235000005911 diet Nutrition 0.000 description 2
230000037213 diet Effects 0.000 description 2
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
229940043237 diethanolamine Drugs 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
238000005534 hematocrit Methods 0.000 description 2
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
235000019371 penicillin G benzathine Nutrition 0.000 description 2
229960005141 piperazine Drugs 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
230000009466 transformation Effects 0.000 description 2
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
229960000281 trometamol Drugs 0.000 description 2
208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
238000003828 vacuum filtration Methods 0.000 description 2
BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
VWVZFHRDLPHBEG-UHFFFAOYSA-N 1-(chloromethyl)-4-methylsulfanylbenzene Chemical group CSC1=CC=C(CCl)C=C1 VWVZFHRDLPHBEG-UHFFFAOYSA-N 0.000 description 1
DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
CBNCUJBMJUQLMT-UHFFFAOYSA-N 4-[(2-propan-2-yl-1,3-benzoxazol-5-yl)methoxy]benzaldehyde Chemical compound C=1C=C2OC(C(C)C)=NC2=CC=1COC1=CC=C(C=O)C=C1 CBNCUJBMJUQLMT-UHFFFAOYSA-N 0.000 description 1
QIOINUYDVDNIRG-UHFFFAOYSA-N 4-[(2-thiophen-2-yl-1,3-benzoxazol-5-yl)methoxy]benzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=C(OC(=N2)C=3SC=CC=3)C2=C1 QIOINUYDVDNIRG-UHFFFAOYSA-N 0.000 description 1
QWDJZKIIHHGRPX-UHFFFAOYSA-N 5-[[4-[(2-propan-2-yl-1,3-benzoxazol-5-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C=1C=C2OC(C(C)C)=NC2=CC=1COC(C=C1)=CC=C1CC1SC(=O)NC1=O QWDJZKIIHHGRPX-UHFFFAOYSA-N 0.000 description 1
HEGLAWCUSKZEAI-UHFFFAOYSA-N 5-[[4-[(2-propyl-1,3-benzoxazol-5-yl)methoxy]phenyl]methyl]-3-trityl-1,3-oxazolidine-2,4-dione Chemical compound C=1C=C2OC(CCC)=NC2=CC=1COC(C=C1)=CC=C1CC(C1=O)OC(=O)N1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 HEGLAWCUSKZEAI-UHFFFAOYSA-N 0.000 description 1
ZGYPLFXBMDYOBL-UHFFFAOYSA-N 5-[[4-[(2-thiophen-2-yl-1,3-benzoxazol-5-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCC1=CC=C(OC(=N2)C=3SC=CC=3)C2=C1 ZGYPLFXBMDYOBL-UHFFFAOYSA-N 0.000 description 1
125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
FZKKPKRWTSYXLF-UHFFFAOYSA-N AL-321 Chemical class C=1C=CC=CC=1C(C)(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O FZKKPKRWTSYXLF-UHFFFAOYSA-N 0.000 description 1
229940123208 Biguanide Drugs 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
239000004380 Cholic acid Substances 0.000 description 1
206010010071 Coma Diseases 0.000 description 1
241001480079 Corymbia calophylla Species 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
102000005548 Hexokinase Human genes 0.000 description 1
108700040460 Hexokinases Proteins 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
108010028554 LDL Cholesterol Proteins 0.000 description 1
235000006552 Liquidambar styraciflua Nutrition 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
VNQABZCSYCTZMS-UHFFFAOYSA-N Orthoform Chemical compound COC(=O)C1=CC=C(O)C(N)=C1 VNQABZCSYCTZMS-UHFFFAOYSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
108010062497 VLDL Lipoproteins Proteins 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
229960001466 acetohexamide Drugs 0.000 description 1
VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
150000004283 biguanides Chemical class 0.000 description 1
125000005997 bromomethyl group Chemical group 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000005018 casein Substances 0.000 description 1
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
235000021240 caseins Nutrition 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
229960001761 chlorpropamide Drugs 0.000 description 1
BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
235000019416 cholic acid Nutrition 0.000 description 1
229960002471 cholic acid Drugs 0.000 description 1
YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
229950009226 ciglitazone Drugs 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
230000000994 depressogenic effect Effects 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
SLFUXNFVAANERW-UHFFFAOYSA-N ethyl hexanoate;potassium Chemical compound [K].CCCCCC(=O)OCC SLFUXNFVAANERW-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
238000000605 extraction Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
235000015220 hamburgers Nutrition 0.000 description 1
ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
230000007794 irritation Effects 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
AXLHVTKGDPVANO-UHFFFAOYSA-N methyl 2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)C(N)CNC(=O)OC(C)(C)C AXLHVTKGDPVANO-UHFFFAOYSA-N 0.000 description 1
WIYPFKLSGGTQBQ-UHFFFAOYSA-N methyl 2-propan-2-yl-1,3-benzoxazole-5-carboxylate Chemical compound COC(=O)C1=CC=C2OC(C(C)C)=NC2=C1 WIYPFKLSGGTQBQ-UHFFFAOYSA-N 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
DCOWODXEBRWFEL-UHFFFAOYSA-N n-benzyl-2-phenylethanamine;n-ethylethanamine Chemical compound CCNCC.C=1C=CC=CC=1CNCCC1=CC=CC=C1 DCOWODXEBRWFEL-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
238000010606 normalization Methods 0.000 description 1
239000003538 oral antidiabetic agent Substances 0.000 description 1
238000003305 oral gavage Methods 0.000 description 1
229940127209 oral hypoglycaemic agent Drugs 0.000 description 1
229950006098 orthocaine Drugs 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
229960003243 phenformin Drugs 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
229910001023 sodium amalgam Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000011775 sodium fluoride Substances 0.000 description 1
235000013024 sodium fluoride Nutrition 0.000 description 1
239000012453 solvate Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000005504 styryl group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229960002277 tolazamide Drugs 0.000 description 1
OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
229960005371 tolbutamide Drugs 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
150000003722 vitamin derivatives Chemical class 0.000 description 1
239000008096 xylene Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- 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
- A61P3/06—Antihyperlipidemics
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Diabetes (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Hematology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Obesity (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Thiazole And Isothizaole Compounds (AREA)
Paints Or Removers (AREA)
Silver Salt Photography Or Processing Solution Therefor (AREA)

IL9830091A 1990-06-05 1991-05-29 Oxa- and thiazolidinedione hypoglycemic and hypocholesterolemic compounds and pharmaceutical preparations containing them IL98300A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US07/533,615 US5037842A (en)	1990-06-05	1990-06-05	Oxa- and thiazolidinedione hypoglycemic and hypocholesterolemic agents

Publications (2)

Publication Number	Publication Date
IL98300A0 IL98300A0 (en)	1992-06-21
IL98300A true IL98300A (en)	1996-01-31

Family

ID=24126737

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9830091A IL98300A (en)	1990-06-05	1991-05-29	Oxa- and thiazolidinedione hypoglycemic and hypocholesterolemic compounds and pharmaceutical preparations containing them

Country Status (20)

Country	Link
US (1)	US5037842A (de)
EP (1)	EP0537300B1 (de)
JP (1)	JPH0714924B2 (de)
AT (1)	ATE121736T1 (de)
AU (1)	AU640284B2 (de)
CA (1)	CA2084195A1 (de)
DE (1)	DE69109291T2 (de)
DK (1)	DK0537300T3 (de)
ES (1)	ES2071339T3 (de)
FI (1)	FI94756C (de)
HU (1)	HUT65676A (de)
IE (1)	IE65628B1 (de)
IL (1)	IL98300A (de)
MY (1)	MY135758A (de)
NO (1)	NO924696D0 (de)
NZ (1)	NZ238382A (de)
PT (1)	PT97856A (de)
TW (1)	TW200481B (de)
WO (1)	WO1991019704A2 (de)
ZA (1)	ZA914188B (de)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5089514A (en) *	1990-06-14	1992-02-18	Pfizer Inc.	3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents
GB9017218D0 (en) *	1990-08-06	1990-09-19	Beecham Group Plc	Novel compounds
NO179246C (no) *	1991-11-20	1996-09-04	Sankyo Co	Aromatiske amino-alkoholderivater og mellomprodukter til fremstilling derav
US5498621A (en) *	1992-05-01	1996-03-12	Pfizer Inc.	Oxazolidinedione hypoglycemic agents
ES2139633T3 (es) *	1992-08-31	2000-02-16	Sankyo Co	Derivados de oxazolidina con propiedades anti-diabetica y anti-obesidad, su preparacion y su utilizacion terapeutica.
US5594016A (en) *	1992-12-28	1997-01-14	Mitsubishi Chemical Corporation	Naphthalene derivatives
TW268952B (de)	1993-02-26	1996-01-21	Takeda Pharm Industry Co Ltd
AU668818B2 (en) *	1993-04-07	1996-05-16	Taiho Pharmaceutical Co., Ltd.	Thiazolidine derivative and pharmaceutical composition containing the same
JP3300869B2 (ja)	1993-08-09	2002-07-08	武田薬品工業株式会社	２，４−オキサゾリジンジオン誘導体、その製造法およびそれを含んでなる医薬組成物
US5641796A (en) *	1994-11-01	1997-06-24	Eli Lilly And Company	Oral hypoglycemic agents
US5925656A (en) *	1995-04-10	1999-07-20	Dr. Reddy's Research Foundation	Compounds having antidiabetic, hypolipidemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
US5801173A (en) *	1996-05-06	1998-09-01	Dr. Reddy's Research Foundation	Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
ZA973848B (en) *	1996-05-06	1997-12-02	Reddy Research Foundation	Novel heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them.
US5919782A (en) *	1996-05-06	1999-07-06	Dr. Reddy's Research Foundation	Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
US5889025A (en) *	1996-05-06	1999-03-30	Reddy's Research Foundation	Antidiabetic compounds having hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
US6114526A (en) *	1996-07-01	2000-09-05	Dr. Reddy's Research Foundation	Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
US6372750B2 (en) *	1996-07-01	2002-04-16	Dr. Reddy's Research Foundation	Heterocyclic compounds, process for their preparation and pharmaceutical compounds containing them and their use in the treatment of diabetes and related diseases
US5885997A (en) *	1996-07-01	1999-03-23	Dr. Reddy's Research Foundation	Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
USRE39266E1 (en) *	1996-07-01	2006-09-05	Dr. Reddy's Laboratories, Limited	Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
CA2258949C (en)	1996-07-01	2008-05-06	Reddy-Cheminor, Inc.	Novel heterocyclic compounds process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
US6313113B1 (en)	1997-04-15	2001-11-06	Reddy-Cheminor, Inc.	Heterocyclic compounds having antidiabetic, hypolipidemic and antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
EP0894089B9 (de) *	1997-05-02	2003-04-02	Dr. Reddy's Laboratories Ltd.	Neue heterozyklische verbindungen mit antidiabetischen, hypolipiddaemischen und blutdrucksenkenden eigenschaften, verfahren zu ihrer herstellung und pharmazeutische zusammensetzungen die diese enthalten
DE69727837T2 (de) *	1997-05-02	2004-12-30	Dr. Reddy's Research Foundation, Hyderabad	Neue antidiabetische verbindungen mit hypolipidimischen und antihypertensiven eigenschaften, verfahren zu ihrer herstellung und ihre enthaltenden arzneimittel
US6011031A (en) *	1997-05-30	2000-01-04	Dr. Reddy's Research Foundation	Azolidinediones useful for the treatment of diabetes, dyslipidemia and hypertension: process for their preparation and pharmaceutical compositions containing them
EP0977753A1 (de) *	1997-12-02	2000-02-09	Dr. Reddy's Research Foundation	Azolidinedione-derivate zur bekämpfung von diabetes, dislipämie und hypertonie
JP2003040877A (ja) *	2001-07-24	2003-02-13	Sumika Fine Chemicals Co Ltd	５−［６−（２−フルオロベンジルオキシ）−２−ナフチル］メチル−２，４−チアゾリジンジオンの製造方法及びその精製方法
CA2800237C (en) *	2002-12-19	2016-05-17	The Scripps Research Institute	Compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding
WO2005113523A1 (en) *	2004-05-20	2005-12-01	Foldrx Pharmaceuticals, Inc.	2-((hetero) aryl)-benzoxazole compounds and derivatives, compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding
WO2008034016A2 (en) *	2006-09-15	2008-03-20	Foldrx Pharmaceuticals, Inc.	Assays for detecting native-state proteins and identifying compounds that modulate the stability of native-state proteins
EA016887B1 (ru)	2007-03-07	2012-08-30	Янссен Фармацевтика Н.В.	ЗАМЕЩЁННЫЕ ФЕНОКСИАМИНОТИАЗОЛОНЫ В КАЧЕСТВЕ МОДУЛЯТОРОВ РОДСТВЕННОГО ЭСТРОГЕНОВОМУ РЕЦЕПТОРУ РЕЦЕПТОРА-α
CL2008000669A1 (es) *	2007-03-07	2008-11-03	Janssen Pharmaceutica Nv	Compuestos derivados de tiazolidindionas n alquiladas, moduladores del receptor alfa relacionados con estrogenos; composicion farmaceutica; y su uso para tratar enfermedades relacionadas con los huesos, cancer, sindrome metabolicos, entre otras.
NZ579372A (en)	2007-03-07	2012-02-24	Janssen Pharmaceutica Nv	Substituted phenoxy thiazolidinediones as estrogen related receptor-alpha modulators
WO2009158118A2 (en) *	2008-05-30	2009-12-30	University Of Notre Dame Du Lac	Anti-bacterial agents from benzo[d]heterocyclic scaffolds for prevention and treatment of multidrug resistant bacteria
AU2010330894A1 (en)	2009-12-18	2012-07-05	Janssen Pharmaceutica Nv	Substituted aminothiazolone indazoles as estrogen related receptor-aalpha modulators
RU2586330C2 (ru)	2011-09-16	2016-06-10	Пфайзер Инк.	Твердые формы ингибитора диссоциации транстиретина
WO2016021706A1 (ja) *	2014-08-08	2016-02-11	カズマパートナーズ株式会社	縮合複素環化合物

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5430171A (en) *	1977-08-10	1979-03-06	Taiho Pharmaceutical Co Ltd	Isooxazole derivative and production
JPS5522636A (en) *	1978-08-04	1980-02-18	Takeda Chem Ind Ltd	Thiazoliding derivative
US4753956A (en) *	1981-01-02	1988-06-28	Pfizer Inc.	Hypoglycemic 5-substituted oxazolidine-2,4-diones
US4689336A (en) *	1981-01-02	1987-08-25	Pfizer Inc.	Hypoglycemic 5-substituted oxazolidine 2,4-diones
US4550172A (en) *	1984-09-21	1985-10-29	American Home Products Corporation	Novel heterocyclic compounds as antiallergic agents
CN1003445B (zh) *	1984-10-03	1989-03-01	武田药品工业株式会社	噻唑烷二酮衍生物，其制备方法和用途
HU210339B (en) *	1985-05-21	1995-03-28	Pfizer	Process for preparing thiazolidinediones and their pharmaceutical compositions haring hypoglycemic effect
JPH06779B2 (ja) *	1985-06-10	1994-01-05	武田薬品工業株式会社	チアゾリジオン誘導体およびそれを含んでなる医薬組成物
JPS62234085A (ja) *	1985-12-18	1987-10-14	Sankyo Co Ltd	チアゾリジン誘導体を有効成分とする糖尿病性合併症治療剤
FI91869C (fi) *	1987-03-18	1994-08-25	Tanabe Seiyaku Co	Menetelmä antidiabeettisena aineena käytettävien bensoksatsolijohdannaisten valmistamiseksi
EP0842925A1 (de) *	1987-09-04	1998-05-20	Beecham Group Plc	Substituierte Thiazolidindionderivate
US4791125A (en) *	1987-12-02	1988-12-13	Pfizer Inc.	Thiazolidinediones as hypoglycemic and anti-atherosclerosis agents
WO1989008650A1 (en) *	1988-03-08	1989-09-21	Pfizer Inc.	Thiazolidinedione hypoglycemic agents

1990
- 1990-06-05 US US07/533,615 patent/US5037842A/en not_active Expired - Lifetime
1991
- 1991-05-20 DE DE69109291T patent/DE69109291T2/de not_active Expired - Fee Related
- 1991-05-20 HU HU9203837A patent/HUT65676A/hu unknown
- 1991-05-20 WO PCT/US1991/003541 patent/WO1991019704A2/en not_active Ceased
- 1991-05-20 ES ES91918661T patent/ES2071339T3/es not_active Expired - Lifetime
- 1991-05-20 DK DK91918661.9T patent/DK0537300T3/da active
- 1991-05-20 CA CA002084195A patent/CA2084195A1/en not_active Abandoned
- 1991-05-20 EP EP91918661A patent/EP0537300B1/de not_active Expired - Lifetime
- 1991-05-20 JP JP3517780A patent/JPH0714924B2/ja not_active Expired - Fee Related
- 1991-05-20 AT AT91918661T patent/ATE121736T1/de not_active IP Right Cessation
- 1991-05-20 AU AU87531/91A patent/AU640284B2/en not_active Ceased
- 1991-05-28 TW TW080104192A patent/TW200481B/zh active
- 1991-05-29 IL IL9830091A patent/IL98300A/en not_active IP Right Cessation
- 1991-06-03 ZA ZA914188A patent/ZA914188B/xx unknown
- 1991-06-04 IE IE188591A patent/IE65628B1/en not_active IP Right Cessation
- 1991-06-04 MY MYPI91000991A patent/MY135758A/en unknown
- 1991-06-04 NZ NZ238382A patent/NZ238382A/en unknown
- 1991-06-04 PT PT97856A patent/PT97856A/pt not_active Application Discontinuation
1992
- 1992-12-04 FI FI925522A patent/FI94756C/fi not_active IP Right Cessation
- 1992-12-04 NO NO924696A patent/NO924696D0/no unknown

Also Published As

Publication number	Publication date
HUT65676A (en)	1994-07-28
DK0537300T3 (da)	1995-07-03
NZ238382A (en)	1995-12-21
IL98300A0 (en)	1992-06-21
FI94756B (fi)	1995-07-14
JPH05506456A (ja)	1993-09-22
IE65628B1 (en)	1995-11-01
PT97856A (pt)	1992-03-31
WO1991019704A2 (en)	1991-12-26
DE69109291T2 (de)	1995-08-31
AU640284B2 (en)	1993-08-19
MY135758A (en)	2008-06-30
TW200481B (de)	1993-02-21
EP0537300A1 (de)	1993-04-21
ES2071339T3 (es)	1995-06-16
ATE121736T1 (de)	1995-05-15
WO1991019704A3 (en)	1992-03-19
ZA914188B (en)	1993-01-27
US5037842A (en)	1991-08-06
CA2084195A1 (en)	1991-12-06
NO924696L (no)	1992-12-04
JPH0714924B2 (ja)	1995-02-22
DE69109291D1 (de)	1995-06-01
FI925522L (fi)	1992-12-04
NO924696D0 (no)	1992-12-04
HU9203837D0 (en)	1993-03-29
AU8753191A (en)	1992-01-07
FI94756C (fi)	1995-10-25
EP0537300B1 (de)	1995-04-26
FI925522A0 (fi)	1992-12-04
IE911885A1 (en)	1991-12-18

Legal Events

Date	Code	Title	Description
1996-07-23	FF	Patent granted
1998-04-05	RH	Patent void

Publication	Publication Date	Title
EP0537300B1 (de)	1995-04-26	Oxazolidindione als hypoglykämische und hypocholesterolämische Wirkstoffe
CA2029703C (en)	1996-10-15	Oxazolidinedione hypoglycemic agents
US5330998A (en)	1994-07-19	Thiazolidinedione derivatives as hypoglycemic agents
US5498621A (en)	1996-03-12	Oxazolidinedione hypoglycemic agents
RU2122002C1 (ru)	1998-11-20	Новые тиазолидиндионы и содержащие их лекарственные средства
US5036079A (en)	1991-07-30	Hypoglycemic thiazolidinedione derivatives
EP0389699B1 (de)	1994-05-11	Thiazolidin-Derivate als hypoglykämisches Mittel
AU665775B2 (en)	1996-01-18	Hypoglycemic thiazolidinediones and intermediates
US4968707A (en)	1990-11-06	Oxazolidin-2-one derivatives as hypoglycemic agents
US5130379A (en)	1992-07-14	Hypoglycemic thiazolidinedione derivatives
EP0591252B1 (de)	1996-09-11	Thiazolidindione als hypoglykämische wirkstoffe
US5401761A (en)	1995-03-28	Thiazolidinedione hypoglycemic agents
WO1991003474A1 (en)	1991-03-21	Hypoglycemic thiazolidinedione derivatives
IE63187B1 (en)	1995-03-22	Thiazolidinedione derivatives as hypoglycemic agents