UA79755C2 - Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation - Google Patents
Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation Download PDFInfo
- Publication number
- UA79755C2 UA79755C2 UA2004021375A UA2004021375A UA79755C2 UA 79755 C2 UA79755 C2 UA 79755C2 UA 2004021375 A UA2004021375 A UA 2004021375A UA 2004021375 A UA2004021375 A UA 2004021375A UA 79755 C2 UA79755 C2 UA 79755C2
- Authority
- UA
- Ukraine
- Prior art keywords
- dihydro
- methyl
- ethoxy
- inden
- alkyl
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 117
- 238000002360 preparation method Methods 0.000 title abstract description 78
- BUVKILSTJGGJJN-UHFFFAOYSA-N acetic acid;2,3-dihydro-1h-indene Chemical class CC(O)=O.C1=CC=C2CCCC2=C1 BUVKILSTJGGJJN-UHFFFAOYSA-N 0.000 title abstract 2
- 239000008177 pharmaceutical agent Substances 0.000 title 1
- 239000012450 pharmaceutical intermediate Substances 0.000 title 1
- 238000011282 treatment Methods 0.000 claims abstract description 34
- 201000010099 disease Diseases 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
- 208000008589 Obesity Diseases 0.000 claims abstract description 7
- 230000003143 atherosclerotic effect Effects 0.000 claims abstract description 7
- 235000020824 obesity Nutrition 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 242
- 125000001424 substituent group Chemical group 0.000 claims description 168
- -1 methylenedioxyphenyl Chemical group 0.000 claims description 162
- 239000000203 mixture Substances 0.000 claims description 133
- 125000000217 alkyl group Chemical group 0.000 claims description 117
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 85
- 150000003839 salts Chemical class 0.000 claims description 72
- 239000002904 solvent Substances 0.000 claims description 64
- 229910052731 fluorine Inorganic materials 0.000 claims description 59
- 150000002148 esters Chemical class 0.000 claims description 58
- 239000011737 fluorine Substances 0.000 claims description 56
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 54
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 52
- 125000004043 oxo group Chemical group O=* 0.000 claims description 52
- 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 claims description 49
- 125000002971 oxazolyl group Chemical group 0.000 claims description 49
- 125000000335 thiazolyl group Chemical group 0.000 claims description 48
- 125000001544 thienyl group Chemical group 0.000 claims description 48
- 239000002585 base Substances 0.000 claims description 47
- 125000004076 pyridyl group Chemical group 0.000 claims description 47
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 47
- 125000002541 furyl group Chemical group 0.000 claims description 46
- 125000002883 imidazolyl group Chemical group 0.000 claims description 46
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 46
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 45
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 45
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 45
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 45
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 45
- 125000001425 triazolyl group Chemical group 0.000 claims description 45
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 44
- 125000003386 piperidinyl group Chemical group 0.000 claims description 44
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 44
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 125000004193 piperazinyl group Chemical group 0.000 claims description 41
- 239000002253 acid Substances 0.000 claims description 40
- 125000002757 morpholinyl group Chemical group 0.000 claims description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 37
- 150000002367 halogens Chemical class 0.000 claims description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 34
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 33
- 125000001041 indolyl group Chemical group 0.000 claims description 32
- 239000003054 catalyst Substances 0.000 claims description 29
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 29
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- 239000003153 chemical reaction reagent Substances 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 125000001624 naphthyl group Chemical group 0.000 claims description 27
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 27
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 26
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 26
- 229940125396 insulin Drugs 0.000 claims description 25
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 claims description 24
- 102000004877 Insulin Human genes 0.000 claims description 24
- 108090001061 Insulin Proteins 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 22
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 21
- 239000003937 drug carrier Substances 0.000 claims description 21
- 238000005984 hydrogenation reaction Methods 0.000 claims description 21
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 21
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 21
- 125000005493 quinolyl group Chemical group 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 20
- 239000003472 antidiabetic agent Substances 0.000 claims description 19
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 125000004597 dihydrobenzothiopyranyl group Chemical group S1C(CCC2=C1C=CC=C2)* 0.000 claims description 19
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 239000007864 aqueous solution Substances 0.000 claims description 18
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 18
- 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 18
- 125000004586 dihydrobenzopyranyl group Chemical group O1C(CCC2=C1C=CC=C2)* 0.000 claims description 18
- 229940126904 hypoglycaemic agent Drugs 0.000 claims description 18
- 238000001953 recrystallisation Methods 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 238000000926 separation method Methods 0.000 claims description 17
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 16
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 15
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 15
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 15
- 125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 claims description 14
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 13
- KHUXNRRPPZOJPT-UHFFFAOYSA-N phenoxy radical Chemical group O=C1C=C[CH]C=C1 KHUXNRRPPZOJPT-UHFFFAOYSA-N 0.000 claims description 13
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 11
- 150000007522 mineralic acids Chemical class 0.000 claims description 11
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 230000003914 insulin secretion Effects 0.000 claims description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 9
- 229940100389 Sulfonylurea Drugs 0.000 claims description 8
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 8
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 229910052796 boron Inorganic materials 0.000 claims description 7
- 238000002955 isolation Methods 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 7
- 235000001258 Cinchona calisaya Nutrition 0.000 claims description 6
- 239000000556 agonist Substances 0.000 claims description 6
- 239000003316 glycosidase inhibitor Substances 0.000 claims description 6
- 229960000948 quinine Drugs 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- KNXVOGGZOFOROK-UHFFFAOYSA-N trimagnesium;dioxido(oxo)silane;hydroxy-oxido-oxosilane Chemical compound [Mg+2].[Mg+2].[Mg+2].O[Si]([O-])=O.O[Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O KNXVOGGZOFOROK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 230000001965 increasing effect Effects 0.000 claims description 5
- 235000019260 propionic acid Nutrition 0.000 claims description 5
- 102000003746 Insulin Receptor Human genes 0.000 claims description 4
- 108010001127 Insulin Receptor Proteins 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 4
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 claims description 4
- KMPWYEUPVWOPIM-LSOMNZGLSA-N cinchonine Chemical compound C1=CC=C2C([C@@H]([C@H]3N4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-LSOMNZGLSA-N 0.000 claims description 4
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 claims description 3
- 239000004912 1,5-cyclooctadiene Substances 0.000 claims description 3
- 238000011084 recovery Methods 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003613 bile acid Substances 0.000 claims description 2
- 230000027455 binding Effects 0.000 claims description 2
- 229940125753 fibrate Drugs 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 6
- 102000013275 Somatomedins Human genes 0.000 claims 3
- MUHONFFTSOCMDH-JXNOXZOESA-N (1z,5z)-cycloocta-1,5-diene;iridium;methyl(diphenyl)phosphane;hexafluorophosphate Chemical compound [Ir].F[P-](F)(F)(F)(F)F.C\1C\C=C/CC\C=C/1.C=1C=CC=CC=1P(C)C1=CC=CC=C1.C=1C=CC=CC=1P(C)C1=CC=CC=C1 MUHONFFTSOCMDH-JXNOXZOESA-N 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
- 125000004987 dibenzofuryl group Chemical group C1(=CC=CC=2OC3=C(C21)C=CC=C3)* 0.000 claims 2
- 239000011995 wilkinson's catalyst Substances 0.000 claims 2
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims 1
- YVOBBFQJMOGQOU-UHFFFAOYSA-N 5-nitro-2,3-dihydrophthalazine-1,4-dione Chemical compound O=C1NNC(=O)C2=C1C([N+](=O)[O-])=CC=C2 YVOBBFQJMOGQOU-UHFFFAOYSA-N 0.000 claims 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
- 230000004927 fusion Effects 0.000 claims 1
- 239000002815 homogeneous catalyst Substances 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 1
- CLKZWXHKFXZIMA-UHFFFAOYSA-N pyrinuron Chemical group C1=CC([N+](=O)[O-])=CC=C1NC(=O)NCC1=CC=CN=C1 CLKZWXHKFXZIMA-UHFFFAOYSA-N 0.000 claims 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 claims 1
- 230000000707 stereoselective effect Effects 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 10
- 208000031226 Hyperlipidaemia Diseases 0.000 abstract description 4
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 abstract 2
- 238000005481 NMR spectroscopy Methods 0.000 description 143
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- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
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- 230000000699 topical effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
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- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
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- 150000003672 ureas Chemical class 0.000 description 1
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- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
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- 229960001729 voglibose Drugs 0.000 description 1
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- 238000009736 wetting Methods 0.000 description 1
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- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
- C07C51/44—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation by distillation
-
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/72—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
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- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
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- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
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- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers
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- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/28—Radicals substituted by nitrogen atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Crystallography & Structural Chemistry (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US37304802P | 2002-04-16 | 2002-04-16 | |
PCT/US2002/023614 WO2003011842A1 (en) | 2001-07-27 | 2002-07-25 | Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
UA79755C2 true UA79755C2 (en) | 2007-07-25 |
Family
ID=29250951
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UA2004021375A UA79755C2 (en) | 2002-04-16 | 2002-07-25 | Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation |
Country Status (7)
Country | Link |
---|---|
US (1) | US7476742B2 (ja) |
EP (1) | EP1497271A1 (ja) |
JP (1) | JP4530668B2 (ja) |
AU (1) | AU2003221960A1 (ja) |
CA (1) | CA2482714A1 (ja) |
UA (1) | UA79755C2 (ja) |
WO (1) | WO2003089418A1 (ja) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004011446A1 (en) * | 2002-07-26 | 2004-02-05 | Bayer Pharmaceuticals Corporation | Indane, dihydrobenzofuran, and tetrahydronaphthalene carboxylic acid derivatives and their use as antidiabetics |
KR101089904B1 (ko) | 2002-12-19 | 2011-12-05 | 더 스크립스 리서치 인스티튜트 | 트란스타이레틴 안정화 및 트란스타이레틴 미스폴딩 저해용조성물 및 방법 |
US7714004B2 (en) | 2002-12-20 | 2010-05-11 | Bayer Pharmaceuticals Corporation | Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation |
US7820837B2 (en) | 2003-05-30 | 2010-10-26 | Takeda Pharmaceutical Company Limited | Condensed ring compound |
DE102004003812A1 (de) * | 2004-01-25 | 2005-08-11 | Aventis Pharma Deutschland Gmbh | Arylsubstituierte Heterozyklen, Verfahren ihrer Herstellung und ihre Verwendung als Arzneimittel |
US7319108B2 (en) | 2004-01-25 | 2008-01-15 | Sanofi-Aventis Deutschland Gmbh | Aryl-substituted heterocycles, process for their preparation and their use as medicaments |
AU2005236055B2 (en) * | 2004-04-20 | 2011-10-06 | Transtech Pharma, Llc | Substituted thiazole and pyrimidine derivatives as melanocortin receptor modulators |
MXPA06013381A (es) | 2004-05-20 | 2007-03-01 | Scripps Research Inst | Estabilizacion de transtiretina. |
SG2014013270A (en) | 2011-09-16 | 2014-05-29 | Pfizer | Solid forms of a transthyretin dissociation inhibitor |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999011255A1 (fr) * | 1997-08-28 | 1999-03-11 | Ono Pharmaceutical Co., Ltd. | Regulateurs du recepteur active par les agents de proliferation des peroxysomes |
AU7073400A (en) | 1999-08-27 | 2001-03-26 | Eli Lilly And Company | Biaryl-oxa(thia)zole derivatives and their use as ppars modulators |
JP2001354671A (ja) * | 2000-04-14 | 2001-12-25 | Nippon Chemiphar Co Ltd | ペルオキシソーム増殖剤応答性受容体δの活性化剤 |
CA2420178A1 (en) * | 2000-08-23 | 2002-03-07 | Eli Lilly And Company | Oxazolyl-aryloxyacetic acid derivatives and their use as ppar agonists |
AU2001280187A1 (en) * | 2000-08-28 | 2002-03-13 | Toray Industries, Inc. | Cyclic amine derivatives |
AR036237A1 (es) * | 2001-07-27 | 2004-08-25 | Bayer Corp | Derivados del acido indan acetico, intermediarios, y metodo para su preparacion, composicion farmaceutica y el uso de dichos derivados para la manufactura de un medicamento |
-
2002
- 2002-07-25 UA UA2004021375A patent/UA79755C2/uk unknown
-
2003
- 2003-04-16 EP EP03718423A patent/EP1497271A1/en not_active Withdrawn
- 2003-04-16 US US10/506,270 patent/US7476742B2/en not_active Expired - Fee Related
- 2003-04-16 WO PCT/US2003/011725 patent/WO2003089418A1/en active Application Filing
- 2003-04-16 CA CA002482714A patent/CA2482714A1/en not_active Abandoned
- 2003-04-16 JP JP2003586139A patent/JP4530668B2/ja not_active Expired - Fee Related
- 2003-04-16 AU AU2003221960A patent/AU2003221960A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
US7476742B2 (en) | 2009-01-13 |
EP1497271A1 (en) | 2005-01-19 |
US20050107392A1 (en) | 2005-05-19 |
WO2003089418A1 (en) | 2003-10-30 |
WO2003089418A8 (en) | 2005-03-03 |
CA2482714A1 (en) | 2003-10-30 |
JP4530668B2 (ja) | 2010-08-25 |
AU2003221960A1 (en) | 2003-11-03 |
JP2005526834A (ja) | 2005-09-08 |
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