OA12035A - Methods of reducing serum glucose and triglyceridelevels and for inhibiting angiogenesis using substituted indolealkanoic acids. - Google Patents

Methods of reducing serum glucose and triglyceridelevels and for inhibiting angiogenesis using substituted indolealkanoic acids. Download PDF

Info

Publication number: OA12035A
Authority: OA; OAPI
Prior art keywords: alkyl; fluoro; wich; subscicuced; phenyl
Prior art date: 1998-12-01

Application number

OA00100134A

Other languages

English (en)

Inventor

Jorge Jacot

Janet Sredy

Original Assignee

Inst Or Pharmaceutical Discove

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.)

1998-12-01

Filing date

1999-12-01

Publication date

2006-05-02

1999-12-01 Application filed by Inst Or Pharmaceutical Discove filed Critical Inst Or Pharmaceutical Discove

2006-05-02 Publication of OA12035A publication Critical patent/OA12035A/en

Links

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 title claims abstract description 23
239000008103 glucose Substances 0.000 title claims abstract description 23
239000002253 acid Substances 0.000 title claims abstract description 22
230000033115 angiogenesis Effects 0.000 title claims abstract description 7
230000002401 inhibitory effect Effects 0.000 title claims abstract description 5
238000000034 method Methods 0.000 title abstract description 35
150000007513 acids Chemical class 0.000 title abstract description 5
210000002966 serum Anatomy 0.000 title abstract description 3
150000001875 compounds Chemical class 0.000 claims abstract description 156
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 29
201000001421 hyperglycemia Diseases 0.000 claims abstract description 6
125000000217 alkyl group Chemical group 0.000 claims description 234
125000001153 fluoro group Chemical group F* 0.000 claims description 157
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 141
125000003545 alkoxy group Chemical group 0.000 claims description 130
229910052736 halogen Inorganic materials 0.000 claims description 125
150000002367 halogens Chemical group 0.000 claims description 124
-1 balogen Chemical group 0.000 claims description 122
125000001309 chloro group Chemical group Cl* 0.000 claims description 114
229910052739 hydrogen Inorganic materials 0.000 claims description 99
239000001257 hydrogen Substances 0.000 claims description 98
150000002431 hydrogen Chemical class 0.000 claims description 78
125000003282 alkyl amino group Chemical group 0.000 claims description 59
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 57
229910052760 oxygen Inorganic materials 0.000 claims description 56
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 55
125000005605 benzo group Chemical group 0.000 claims description 52
125000001246 bromo group Chemical group Br* 0.000 claims description 52
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 49
239000001301 oxygen Substances 0.000 claims description 49
125000004076 pyridyl group Chemical group 0.000 claims description 49
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 47
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 45
125000002541 furyl group Chemical group 0.000 claims description 43
229910052717 sulfur Inorganic materials 0.000 claims description 42
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 41
125000000623 heterocyclic group Chemical group 0.000 claims description 38
229910052799 carbon Inorganic materials 0.000 claims description 35
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 30
239000011593 sulfur Substances 0.000 claims description 30
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 28
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 28
229910052757 nitrogen Inorganic materials 0.000 claims description 27
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 27
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
125000002947 alkylene group Chemical group 0.000 claims description 25
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 24
125000004093 cyano group Chemical group *C#N 0.000 claims description 23
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 22
125000001589 carboacyl group Chemical group 0.000 claims description 21
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 20
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 20
125000003118 aryl group Chemical group 0.000 claims description 20
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
125000004432 carbon atom Chemical group C* 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 19
125000002346 iodo group Chemical group I* 0.000 claims description 18
125000001544 thienyl group Chemical group 0.000 claims description 18
125000004414 alkyl thio group Chemical group 0.000 claims description 14
239000003795 chemical substances by application Substances 0.000 claims description 14
229940002612 prodrug Drugs 0.000 claims description 14
239000000651 prodrug Chemical group 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
125000004429 atom Chemical group 0.000 claims description 12
150000002148 esters Chemical class 0.000 claims description 12
235000019000 fluorine Nutrition 0.000 claims description 12
125000001072 heteroaryl group Chemical group 0.000 claims description 12
125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 11
241000124008 Mammalia Species 0.000 claims description 10
125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 10
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 8
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 8
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
239000011737 fluorine Substances 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 7
ONCNIMLKGZSAJT-UHFFFAOYSA-N thieno[3,2-b]furan Chemical compound S1C=CC2=C1C=CO2 ONCNIMLKGZSAJT-UHFFFAOYSA-N 0.000 claims description 7
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
KDZASNPOEXNJBZ-UHFFFAOYSA-N thieno[2,3-d][1,2]thiazole Chemical compound S1N=CC2=C1C=CS2 KDZASNPOEXNJBZ-UHFFFAOYSA-N 0.000 claims description 6
230000029663 wound healing Effects 0.000 claims description 6
241000282414 Homo sapiens Species 0.000 claims description 5
WMUIZUWOEIQJEH-UHFFFAOYSA-N benzo[e][1,3]benzoxazole Chemical compound C1=CC=C2C(N=CO3)=C3C=CC2=C1 WMUIZUWOEIQJEH-UHFFFAOYSA-N 0.000 claims description 5
206010011416 Croup infectious Diseases 0.000 claims description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
KXNQKOAQSGJCQU-UHFFFAOYSA-N benzo[e][1,3]benzothiazole Chemical compound C1=CC=C2C(N=CS3)=C3C=CC2=C1 KXNQKOAQSGJCQU-UHFFFAOYSA-N 0.000 claims description 4
239000000460 chlorine Substances 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
238000002648 combination therapy Methods 0.000 claims description 4
201000010549 croup Diseases 0.000 claims description 4
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 4
229930192474 thiophene Natural products 0.000 claims description 4
KYHVTMFADJNSGS-UHFFFAOYSA-N {3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1h-indol-1-yl}acetic acid Chemical compound C12=CC=CC=C2N(CC(=O)O)C=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 KYHVTMFADJNSGS-UHFFFAOYSA-N 0.000 claims description 3
MGICLRNAZXDKAT-UHFFFAOYSA-N 2-(2-methylindol-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(O)=O)C(C)=CC2=C1 MGICLRNAZXDKAT-UHFFFAOYSA-N 0.000 claims description 2
ILKTWJJFMCHYOZ-UHFFFAOYSA-N 2-[3-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]indol-1-yl]acetic acid Chemical compound C12=CC=CC=C2N(CC(=O)O)C=C1CC1=NC2=CC(C(F)(F)F)=CC=C2S1 ILKTWJJFMCHYOZ-UHFFFAOYSA-N 0.000 claims description 2
QBQAVWVRMZYUGW-UHFFFAOYSA-N 2-[5-methyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid Chemical compound FC1=CC(F)=C2SC(CC3=CN(CC(O)=O)C4=CC=C(C=C43)C)=NC2=C1F QBQAVWVRMZYUGW-UHFFFAOYSA-N 0.000 claims description 2
YAKLHRCDDYEKID-UHFFFAOYSA-N 2-[6-fluoro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid Chemical compound C12=CC=C(F)C=C2N(CC(=O)O)C=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 YAKLHRCDDYEKID-UHFFFAOYSA-N 0.000 claims description 2
IZPJNGSNFRVSDL-UHFFFAOYSA-N 2-[6-methyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid Chemical compound FC1=CC(F)=C2SC(CC=3C4=CC=C(C=C4N(CC(O)=O)C=3)C)=NC2=C1F IZPJNGSNFRVSDL-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
230000001737 promoting effect Effects 0.000 claims description 2
OVCXRBARSPBVMC-UHFFFAOYSA-N triazolopyridine Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1C=1OC=NC=1C1=CC=C(F)C=C1 OVCXRBARSPBVMC-UHFFFAOYSA-N 0.000 claims 5
VJYJJHQEVLEOFL-UHFFFAOYSA-N thieno[3,2-b]thiophene Chemical compound S1C=CC2=C1C=CS2 VJYJJHQEVLEOFL-UHFFFAOYSA-N 0.000 claims 2
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 1
240000005020 Acaciella glauca Species 0.000 claims 1
102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 claims 1
101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 claims 1
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
150000002500 ions Chemical class 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 abstract description 5
230000001684 chronic effect Effects 0.000 abstract description 3
208000031226 Hyperlipidaemia Diseases 0.000 abstract description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 abstract description 2
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 83
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 62
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
239000000203 mixture Substances 0.000 description 44
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 42
239000000243 solution Substances 0.000 description 42
235000019439 ethyl acetate Nutrition 0.000 description 35
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 21
239000000543 intermediate Substances 0.000 description 21
238000012360 testing method Methods 0.000 description 21
MYTGFBZJLDLWQG-UHFFFAOYSA-N 5-chloro-1h-indole Chemical compound ClC1=CC=C2NC=CC2=C1 MYTGFBZJLDLWQG-UHFFFAOYSA-N 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 14
235000019341 magnesium sulphate Nutrition 0.000 description 14
102000016912 Aldehyde Reductase Human genes 0.000 description 13
108010053754 Aldehyde reductase Proteins 0.000 description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 13
229940093499 ethyl acetate Drugs 0.000 description 13
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 13
150000002475 indoles Chemical class 0.000 description 13
239000007787 solid Substances 0.000 description 13
238000003786 synthesis reaction Methods 0.000 description 13
235000011054 acetic acid Nutrition 0.000 description 12
210000004369 blood Anatomy 0.000 description 12
239000008280 blood Substances 0.000 description 12
238000001816 cooling Methods 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
239000000463 material Substances 0.000 description 11
239000011780 sodium chloride Substances 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
241000699670 Mus sp. Species 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
230000000694 effects Effects 0.000 description 10
239000000843 powder Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
208000002249 Diabetes Complications Diseases 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
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239000002585 base Substances 0.000 description 9
206010012655 Diabetic complications Diseases 0.000 description 8
210000000709 aorta Anatomy 0.000 description 8
239000012267 brine Substances 0.000 description 8
239000003112 inhibitor Substances 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
239000000047 product Substances 0.000 description 8
150000003839 salts Chemical class 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
238000003556 assay Methods 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
239000011734 sodium Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 7
239000000725 suspension Substances 0.000 description 7
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
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231100000252 nontoxic Toxicity 0.000 description 6
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239000013641 positive control Substances 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
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229910004373 HOAc Inorganic materials 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
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KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Diabetes (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Obesity (AREA)
Vascular Medicine (AREA)
Endocrinology (AREA)
Urology & Nephrology (AREA)
Dermatology (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

OA00100134A 1998-12-01 1999-12-01 Methods of reducing serum glucose and triglyceridelevels and for inhibiting angiogenesis using substituted indolealkanoic acids. OA12035A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US11039598P	1998-12-01	1998-12-01

Publications (1)

Publication Number	Publication Date
OA12035A true OA12035A (en)	2006-05-02

Family

ID=22332786

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA00100134A OA12035A (en)	1998-12-01	1999-12-01	Methods of reducing serum glucose and triglyceridelevels and for inhibiting angiogenesis using substituted indolealkanoic acids.

Country Status (30)

Country	Link
US (5)	US6555568B1 (fr)
EP (1)	EP1135124B1 (fr)
JP (1)	JP2002531398A (fr)
KR (1)	KR20010086075A (fr)
CN (1)	CN1368883A (fr)
AP (1)	AP2001002146A0 (fr)
AT (1)	ATE265210T1 (fr)
AU (1)	AU770925B2 (fr)
BG (1)	BG105531A (fr)
BR (1)	BR9915882A (fr)
CA (1)	CA2385845A1 (fr)
CZ (1)	CZ20011864A3 (fr)
DE (1)	DE69916881T2 (fr)
DZ (1)	DZ2953A1 (fr)
EE (1)	EE200100296A (fr)
HK (1)	HK1046372A1 (fr)
HU (1)	HUP0104953A3 (fr)
ID (1)	ID30037A (fr)
IL (1)	IL143247A0 (fr)
MX (1)	MXPA02003118A (fr)
NO (1)	NO20012690L (fr)
OA (1)	OA12035A (fr)
PL (1)	PL349016A1 (fr)
SK (1)	SK7352001A3 (fr)
TN (1)	TNSN99224A1 (fr)
TR (1)	TR200101539T2 (fr)
TW (1)	TW584560B (fr)
WO (1)	WO2000032180A2 (fr)
YU (1)	YU40101A (fr)
ZA (1)	ZA200104126B (fr)

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US6521659B2 (en) *	2000-03-02	2003-02-18	Institute For Pharmaceutical Discovery, Llc	Compositions containing a substituted indolealkanoic acid and an angiotensin converting enzyme inhibitor

1999
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- 1999-12-01 IL IL14324799A patent/IL143247A0/xx unknown
- 1999-12-01 TR TR2001/01539T patent/TR200101539T2/xx unknown
- 1999-12-01 DZ DZ990253A patent/DZ2953A1/fr active
- 1999-12-01 SK SK735-2001A patent/SK7352001A3/sk unknown
- 1999-12-01 AU AU21616/00A patent/AU770925B2/en not_active Ceased
- 1999-12-01 PL PL99349016A patent/PL349016A1/xx not_active Application Discontinuation
- 1999-12-01 CZ CZ20011864A patent/CZ20011864A3/cs unknown
- 1999-12-01 AT AT99965955T patent/ATE265210T1/de not_active IP Right Cessation
- 1999-12-01 OA OA00100134A patent/OA12035A/en unknown
- 1999-12-01 KR KR1020017006865A patent/KR20010086075A/ko not_active Withdrawn
- 1999-12-01 DE DE69916881T patent/DE69916881T2/de not_active Expired - Lifetime
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- 1999-12-01 AP APAP/P/2001/002146A patent/AP2001002146A0/en unknown
- 1999-12-01 JP JP2000584876A patent/JP2002531398A/ja active Pending
- 1999-12-01 CA CA002385845A patent/CA2385845A1/fr not_active Abandoned
- 1999-12-01 MX MXPA02003118A patent/MXPA02003118A/es not_active IP Right Cessation
- 1999-12-01 US US09/452,252 patent/US6555568B1/en not_active Expired - Fee Related
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- 1999-12-01 YU YU40101A patent/YU40101A/sh unknown
- 1999-12-01 HK HK02107989.6A patent/HK1046372A1/zh unknown
- 1999-12-01 BR BR9915882-5A patent/BR9915882A/pt not_active IP Right Cessation
- 1999-12-01 WO PCT/US1999/028483 patent/WO2000032180A2/fr not_active Ceased
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- 1999-12-01 HU HU0104953A patent/HUP0104953A3/hu unknown
- 1999-12-01 EP EP99965955A patent/EP1135124B1/fr not_active Expired - Lifetime
2000
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2001
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- 2001-05-31 NO NO20012690A patent/NO20012690L/no not_active Application Discontinuation
2003
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2005
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2010
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2011
- 2011-11-22 US US13/302,906 patent/US20120065203A1/en not_active Abandoned

Also Published As

Publication number	Publication date
ATE265210T1 (de)	2004-05-15
YU40101A (sh)	2005-07-19
EP1135124A2 (fr)	2001-09-26
CZ20011864A3 (cs)	2002-03-13
WO2000032180A2 (fr)	2000-06-08
MXPA02003118A (es)	2004-04-21
SK7352001A3 (en)	2002-06-04
CN1368883A (zh)	2002-09-11
HUP0104953A3 (en)	2002-08-28
US6555568B1 (en)	2003-04-29
AU770925B2 (en)	2004-03-11
EP1135124B1 (fr)	2004-04-28
CA2385845A1 (fr)	2000-06-08
EE200100296A (et)	2003-02-17
DE69916881T2 (de)	2005-02-03
DE69916881D1 (de)	2004-06-03
NO20012690L (no)	2001-07-27
AU2161600A (en)	2000-06-19
WO2000032180A3 (fr)	2000-11-16
DZ2953A1 (fr)	2004-03-15
US20120065203A1 (en)	2012-03-15
ZA200104126B (en)	2002-05-21
US20060074114A1 (en)	2006-04-06
HUP0104953A2 (hu)	2002-07-29
US6964980B2 (en)	2005-11-15
US20030216452A1 (en)	2003-11-20
TR200101539T2 (tr)	2001-12-21
BR9915882A (pt)	2001-08-21
PL349016A1 (en)	2002-06-17
IL143247A0 (en)	2002-04-21
JP2002531398A (ja)	2002-09-24
TNSN99224A1 (fr)	2005-11-10
AP2001002146A0 (en)	2001-06-30
ID30037A (id)	2001-11-01
US20100324105A1 (en)	2010-12-23
BG105531A (en)	2001-12-31
NO20012690D0 (no)	2001-05-31
TW584560B (en)	2004-04-21
KR20010086075A (ko)	2001-09-07
HK1046372A1 (zh)	2003-01-10

Publication	Publication Date	Title
OA12035A (en)	2006-05-02	Methods of reducing serum glucose and triglyceridelevels and for inhibiting angiogenesis using substituted indolealkanoic acids.
CA2383983C (fr)	2009-09-29	Acides indolalcanoiques substitues
RS59600B1 (sr)	2020-01-31	Stabilizovane kompozicije neproteinskog toksina klostridije
US6521659B2 (en)	2003-02-18	Compositions containing a substituted indolealkanoic acid and an angiotensin converting enzyme inhibitor
US20010044437A1 (en)	2001-11-22	Methods for reducing uric acid levels