SK150398A3 - Indole derivatives useful as endothelin receptor antagonists - Google Patents

Indole derivatives useful as endothelin receptor antagonists Download PDF

Info

Publication number: SK150398A3
Authority: SK; Slovakia
Prior art keywords: compound; formula; alkyl; lrms; mmol
Prior art date: 1996-05-09

Application number

SK1503-98A

Other languages

English (en)

Slovak (sk)

Inventor

David J Rawson

Kevin N Dack

Roger P Dickinson

Kim James

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.)

1996-05-09

Filing date

1997-04-11

Publication date

1999-03-12

1997-04-11 Application filed by Pfizer filed Critical Pfizer

1999-03-12 Publication of SK150398A3 publication Critical patent/SK150398A3/sk

Links

239000002308 endothelin receptor antagonist Substances 0.000 title description 8
229940118365 Endothelin receptor antagonist Drugs 0.000 title description 7
150000002475 indoles Chemical class 0.000 title description 5
229940054051 antipsychotic indole derivative Drugs 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 236
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
229910052736 halogen Inorganic materials 0.000 claims abstract description 9
150000002367 halogens Chemical class 0.000 claims abstract description 9
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims abstract description 8
208000002815 pulmonary hypertension Diseases 0.000 claims abstract description 8
208000037803 restenosis Diseases 0.000 claims abstract description 8
208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 7
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 7
201000006370 kidney failure Diseases 0.000 claims abstract description 7
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims abstract description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 5
125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
125000005010 perfluoroalkyl group Chemical group 0.000 claims abstract description 3
125000001424 substituent group Chemical group 0.000 claims abstract description 3
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract 3
-1 alkyl lithium Chemical compound 0.000 claims description 72
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 53
229910052739 hydrogen Inorganic materials 0.000 claims description 48
239000001257 hydrogen Substances 0.000 claims description 46
238000000034 method Methods 0.000 claims description 46
238000006243 chemical reaction Methods 0.000 claims description 43
125000000217 alkyl group Chemical group 0.000 claims description 32
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
229910052757 nitrogen Inorganic materials 0.000 claims description 25
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
150000002431 hydrogen Chemical class 0.000 claims description 21
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 12
239000002841 Lewis acid Substances 0.000 claims description 10
229910002091 carbon monoxide Inorganic materials 0.000 claims description 10
150000007517 lewis acids Chemical class 0.000 claims description 10
229910052760 oxygen Chemical group 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
239000003153 chemical reaction reagent Substances 0.000 claims description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
229910052794 bromium Inorganic materials 0.000 claims description 7
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 6
239000007818 Grignard reagent Substances 0.000 claims description 6
BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 6
239000003054 catalyst Substances 0.000 claims description 6
239000007789 gas Substances 0.000 claims description 6
150000004795 grignard reagents Chemical class 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
229920006395 saturated elastomer Polymers 0.000 claims description 6
229910000077 silane Inorganic materials 0.000 claims description 6
201000001320 Atherosclerosis Diseases 0.000 claims description 5
230000002490 cerebral effect Effects 0.000 claims description 5
206010008118 cerebral infarction Diseases 0.000 claims description 5
208000031225 myocardial ischemia Diseases 0.000 claims description 5
229910052763 palladium Inorganic materials 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
206010002383 Angina Pectoris Diseases 0.000 claims description 4
201000006474 Brain Ischemia Diseases 0.000 claims description 4
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 4
206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
206010008120 Cerebral ischaemia Diseases 0.000 claims description 4
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 4
229930105110 Cyclosporin A Natural products 0.000 claims description 4
108010036949 Cyclosporine Proteins 0.000 claims description 4
206010019280 Heart failures Diseases 0.000 claims description 4
208000006011 Stroke Diseases 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
239000002585 base Substances 0.000 claims description 4
229960001265 ciclosporin Drugs 0.000 claims description 4
229930182912 cyclosporin Natural products 0.000 claims description 4
231100000268 induced nephrotoxicity Toxicity 0.000 claims description 4
239000011593 sulfur Chemical group 0.000 claims description 4
206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
125000000304 alkynyl group Chemical group 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
239000001569 carbon dioxide Substances 0.000 claims description 3
229910002092 carbon dioxide Inorganic materials 0.000 claims description 3
239000003638 chemical reducing agent Substances 0.000 claims description 3
230000000269 nucleophilic effect Effects 0.000 claims description 3
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
230000008569 process Effects 0.000 claims description 3
210000002307 prostate Anatomy 0.000 claims description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
206010020880 Hypertrophy Diseases 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
239000000969 carrier Substances 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
229910052744 lithium Inorganic materials 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
239000001301 oxygen Chemical group 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
125000003342 alkenyl group Chemical group 0.000 claims 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 261
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
239000000243 solution Substances 0.000 description 149
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
238000005481 NMR spectroscopy Methods 0.000 description 70
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 66
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 61
239000000203 mixture Substances 0.000 description 61
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 52
238000003818 flash chromatography Methods 0.000 description 46
239000000047 product Substances 0.000 description 46
239000003480 eluent Substances 0.000 description 44
239000012044 organic layer Substances 0.000 description 42
239000002904 solvent Substances 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
239000007787 solid Substances 0.000 description 34
229910052943 magnesium sulfate Inorganic materials 0.000 description 33
235000019341 magnesium sulphate Nutrition 0.000 description 33
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
239000012299 nitrogen atmosphere Substances 0.000 description 25
239000003921 oil Substances 0.000 description 25
235000019198 oils Nutrition 0.000 description 25
238000010992 reflux Methods 0.000 description 25
239000011541 reaction mixture Substances 0.000 description 24
ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
108050009340 Endothelin Proteins 0.000 description 22
102000002045 Endothelin Human genes 0.000 description 22
125000001041 indolyl group Chemical group 0.000 description 21
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 19
101800004490 Endothelin-1 Proteins 0.000 description 17
102400000686 Endothelin-1 Human genes 0.000 description 17
238000003756 stirring Methods 0.000 description 17
238000012360 testing method Methods 0.000 description 17
238000004458 analytical method Methods 0.000 description 16
239000006260 foam Substances 0.000 description 16
229940124530 sulfonamide Drugs 0.000 description 16
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
210000001519 tissue Anatomy 0.000 description 14
239000012267 brine Substances 0.000 description 13
238000001816 cooling Methods 0.000 description 13
102000005962 receptors Human genes 0.000 description 13
108020003175 receptors Proteins 0.000 description 13
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
150000003456 sulfonamides Chemical class 0.000 description 12
239000000725 suspension Substances 0.000 description 11
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 10
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
241000700159 Rattus Species 0.000 description 10
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical group CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
238000001914 filtration Methods 0.000 description 9
229910000104 sodium hydride Inorganic materials 0.000 description 9
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 8
230000002411 adverse Effects 0.000 description 8
239000005557 antagonist Substances 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
210000000056 organ Anatomy 0.000 description 8
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 7
125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
239000002253 acid Substances 0.000 description 7
235000019270 ammonium chloride Nutrition 0.000 description 7
239000000543 intermediate Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
238000000746 purification Methods 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
GFQPTVGPUTXTBG-UHFFFAOYSA-N 6-bromo-1-ethylindole Chemical compound C1=C(Br)C=C2N(CC)C=CC2=C1 GFQPTVGPUTXTBG-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
239000010410 layer Substances 0.000 description 6
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
239000007858 starting material Substances 0.000 description 6
125000001984 thiazolidinyl group Chemical group 0.000 description 6
PXHJDPPKNUGKPM-UHFFFAOYSA-N 6-bromo-1-methylindole Chemical compound C1=C(Br)C=C2N(C)C=CC2=C1 PXHJDPPKNUGKPM-UHFFFAOYSA-N 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
238000007796 conventional method Methods 0.000 description 5
239000012043 crude product Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000010828 elution Methods 0.000 description 5
239000005457 ice water Substances 0.000 description 5
238000002844 melting Methods 0.000 description 5
230000008018 melting Effects 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
QCVIFBRTTLMEOV-FUKQNADPSA-M sodium;(2r)-2-[[(2r)-2-[[(2s)-2-[[(2s,6r)-2,6-dimethylpiperidine-1-carbonyl]amino]-4,4-dimethylpentanoyl]amino]-3-(1-methoxycarbonylindol-3-yl)propanoyl]amino]hexanoate Chemical compound [Na+].N([C@@H](CC(C)(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2N(C(=O)OC)C=1)C(=O)N[C@H](CCCC)C([O-])=O)C(=O)N1[C@@H](C)CCC[C@H]1C QCVIFBRTTLMEOV-FUKQNADPSA-M 0.000 description 5
239000000126 substance Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical compound BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 4
125000001246 bromo group Chemical group Br* 0.000 description 4
DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 4
239000006185 dispersion Substances 0.000 description 4
229940079593 drug Drugs 0.000 description 4
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 4
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
239000003446 ligand Substances 0.000 description 4
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 4
JGSZAFMDOLKPMY-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)-2-(5-bromo-1-methylindol-3-yl)acetic acid Chemical compound C12=CC(Br)=CC=C2N(C)C=C1C(C(O)=O)C1=CC=C(OCO2)C2=C1 JGSZAFMDOLKPMY-UHFFFAOYSA-N 0.000 description 3
WVOWEROKBOQYLJ-UHFFFAOYSA-N 4-propan-2-ylbenzenesulfonamide Chemical compound CC(C)C1=CC=C(S(N)(=O)=O)C=C1 WVOWEROKBOQYLJ-UHFFFAOYSA-N 0.000 description 3
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239000012528 membrane Substances 0.000 description 1
NMILWYUYIFMKTE-UHFFFAOYSA-N methyl 1-methylindole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CN(C)C2=C1 NMILWYUYIFMKTE-UHFFFAOYSA-N 0.000 description 1
HKVMFHVXIMSZSH-UHFFFAOYSA-N methyl 2-(6-bromo-1-methylindol-3-yl)-2-(6-chloro-1,3-benzodioxol-5-yl)acetate Chemical compound C=1N(C)C2=CC(Br)=CC=C2C=1C(C(=O)OC)C(C(=C1)Cl)=CC2=C1OCO2 HKVMFHVXIMSZSH-UHFFFAOYSA-N 0.000 description 1
JDZWAGRLKDXBGM-UHFFFAOYSA-N methyl 2-(6-bromo-1h-indol-3-yl)-2-(6-chloro-1,3-benzodioxol-5-yl)acetate Chemical compound C=1NC2=CC(Br)=CC=C2C=1C(C(=O)OC)C(C(=C1)Cl)=CC2=C1OCO2 JDZWAGRLKDXBGM-UHFFFAOYSA-N 0.000 description 1
MOVBJUGHBJJKOW-UHFFFAOYSA-N methyl 2-amino-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1N MOVBJUGHBJJKOW-UHFFFAOYSA-N 0.000 description 1
VDCNKTKUSQRHAI-UHFFFAOYSA-N methyl 2-bromo-2-(6-chloro-1,3-benzodioxol-5-yl)acetate Chemical compound C1=C(Cl)C(C(Br)C(=O)OC)=CC2=C1OCO2 VDCNKTKUSQRHAI-UHFFFAOYSA-N 0.000 description 1
YSTOUEVTMBJHHE-UHFFFAOYSA-N methyl 2-bromo-2-(7-methoxy-1,3-benzodioxol-5-yl)acetate Chemical compound COC1=CC(C(Br)C(=O)OC)=CC2=C1OCO2 YSTOUEVTMBJHHE-UHFFFAOYSA-N 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
210000002464 muscle smooth vascular Anatomy 0.000 description 1
JYEOZSLJYJHNHZ-UHFFFAOYSA-N n-tert-butyl-2-ethyl-4-methylbenzenesulfonamide Chemical compound CCC1=CC(C)=CC=C1S(=O)(=O)NC(C)(C)C JYEOZSLJYJHNHZ-UHFFFAOYSA-N 0.000 description 1
230000008692 neointimal formation Effects 0.000 description 1
230000016273 neuron death Effects 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
229910000489 osmium tetroxide Inorganic materials 0.000 description 1
239000012285 osmium tetroxide Substances 0.000 description 1
JNGDFYLGDPAEBY-UHFFFAOYSA-N oxadiazole-4-thione Chemical compound S=C1CON=N1 JNGDFYLGDPAEBY-UHFFFAOYSA-N 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229940081310 piperonal Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
239000003380 propellant Substances 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
210000001147 pulmonary artery Anatomy 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
235000019254 sodium formate Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000011273 tar residue Substances 0.000 description 1
DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical compound O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 1
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero 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
- C07D413/14—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)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Urology & Nephrology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pulmonology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)

SK1503-98A 1996-05-09 1997-04-11 Indole derivatives useful as endothelin receptor antagonists SK150398A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9609641.7A GB9609641D0 (en)	1996-05-09	1996-05-09	Compounds useful in therapy
PCT/EP1997/001882 WO1997043260A1 (en)	1996-05-09	1997-04-11	Indole derivatives useful as endothelin receptor antagonists

Publications (1)

Publication Number	Publication Date
SK150398A3 true SK150398A3 (en)	1999-03-12

Family

ID=10793387

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1503-98A SK150398A3 (en)	1996-05-09	1997-04-11	Indole derivatives useful as endothelin receptor antagonists

Country Status (42)

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US (4)	US6017945A (de)
EP (1)	EP0901470B1 (de)
JP (1)	JP3245179B2 (de)
KR (1)	KR100331217B1 (de)
CN (1)	CN1124262C (de)
AP (1)	AP830A (de)
AR (1)	AR007030A1 (de)
AT (1)	ATE263151T1 (de)
AU (1)	AU717849B2 (de)
BG (1)	BG102873A (de)
BR (1)	BR9709072A (de)
CA (1)	CA2253876A1 (de)
CO (1)	CO4650036A1 (de)
CZ (1)	CZ292928B6 (de)
DE (1)	DE69728392T2 (de)
DK (1)	DK0901470T3 (de)
DZ (1)	DZ2227A1 (de)
EA (1)	EA001471B1 (de)
ES (1)	ES2218675T3 (de)
GB (1)	GB9609641D0 (de)
HN (1)	HN1997000058A (de)
HR (1)	HRP970249B1 (de)
HU (1)	HUP9901245A3 (de)
ID (1)	ID16878A (de)
IL (1)	IL125903A0 (de)
IS (1)	IS1856B (de)
MA (1)	MA26428A1 (de)
NO (1)	NO312547B1 (de)
NZ (1)	NZ332640A (de)
OA (1)	OA10896A (de)
PE (1)	PE65098A1 (de)
PL (1)	PL329725A1 (de)
PT (1)	PT901470E (de)
SI (1)	SI0901470T1 (de)
SK (1)	SK150398A3 (de)
TN (1)	TNSN97078A1 (de)
TR (1)	TR199802269T2 (de)
TW (1)	TW491838B (de)
UA (1)	UA50767C2 (de)
UY (1)	UY24546A1 (de)
WO (1)	WO1997043260A1 (de)
ZA (1)	ZA973963B (de)

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WO2004052856A1 (en)	2002-12-10	2004-06-24	Wyeth	Substituted indole oxo-acetyl amino acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1)
UA80453C2 (en)	2002-12-10	2007-09-25		Derivatives of substituted dyhydropyranoindol-3,4-dion as inhibitors of plasminogen activator inhibitor-1 (pai-1)
BRPI0406883A (pt) *	2003-01-22	2006-01-03	Lilly Co Eli	Composto, composição farmacêutica, método de tratar um distúrbio, e, uso de um composto
US7342039B2 (en)	2003-09-25	2008-03-11	Wyeth	Substituted indole oximes
US7163954B2 (en)	2003-09-25	2007-01-16	Wyeth	Substituted naphthyl benzothiophene acids
US7420083B2 (en)	2003-09-25	2008-09-02	Wyeth	Substituted aryloximes
US7351726B2 (en)	2003-09-25	2008-04-01	Wyeth	Substituted oxadiazolidinediones
US7332521B2 (en)	2003-09-25	2008-02-19	Wyeth	Substituted indoles
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US7582773B2 (en)	2003-09-25	2009-09-01	Wyeth	Substituted phenyl indoles
US7268159B2 (en)	2003-09-25	2007-09-11	Wyeth	Substituted indoles
US7446201B2 (en)	2003-09-25	2008-11-04	Wyeth	Substituted heteroaryl benzofuran acids
US7141592B2 (en)	2003-09-25	2006-11-28	Wyeth	Substituted oxadiazolidinediones
US7411083B2 (en)	2003-09-25	2008-08-12	Wyeth	Substituted acetic acid derivatives
JP2005109006A (ja) *	2003-09-29	2005-04-21	Tdk Corp	高電圧貫通型コンデンサ及びマグネトロン
HN2004000536A (es) *	2003-12-16	2009-02-18	Wyeth Corp	Un procediemiento de sintesis para la alquilacion reductiva de la posicon c-3 de indoles
WO2006023864A1 (en)	2004-08-23	2006-03-02	Wyeth	Pyrrolo-naphthyl acids as pai-1 inhibitors
WO2006023866A2 (en)	2004-08-23	2006-03-02	Wyeth	Thiazolo-naphthyl acids as inhibitors of plasminogen activator inhibitor-1
MX2007002178A (es)	2004-08-23	2007-04-02	Wyeth Corp	Acidos de oxazolo-naftilo como moduladores del inhibidor del activador de plasminogeno tipo 1 (pai-1) util en el tratamiento de trombosis y enfermedades cardiovasculares.
US7683091B2 (en)	2005-08-17	2010-03-23	Wyeth	Substituted indoles and methods of their use
WO2007119214A2 (en) *	2006-04-13	2007-10-25	Actelion Pharmaceuticals Ltd	Endothelin receptor antagonists for early stage idiopathic pulmonary fibrosis
DE102008030207A1 (de)	2008-06-25	2009-12-31	Bayer Schering Pharma Aktiengesellschaft	Substituierte 7-Sulfanylmethyl-, 7-Sulfinylmethyl- und 7-Sulfonylmethyl-Indole und ihre Verwendung
DE102008030206A1 (de)	2008-06-25	2009-12-31	Bayer Schering Pharma Aktiengesellschaft	3-Cyanoalky- und 3-Hydroxyalkyl-Indole und ihre Verwendung
EP3519816A4 (de)	2016-09-29	2020-05-06	The Regents of the University of California	Verbindungen zur erhöhung der neuronalen plastizität
CN106674065A (zh) *	2016-12-07	2017-05-17	贵州大学	一种5‑卤代‑2‑烷氧基‑4‑甲苯磺酰氯制备方法
GB201817038D0 (en) *	2018-10-19	2018-12-05	Inflazome Ltd	Novel processes
KR102946120B1 (ko)	2019-02-27	2026-03-30	더 리젠츠 오브 더 유니버시티 오브 캘리포니아	뇌 장애를 치료하기 위한 아제피노-인돌 및 다른 헤테로사이클
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1996
- 1996-05-09 GB GBGB9609641.7A patent/GB9609641D0/en active Pending
1997
- 1997-04-01 TW TW086104171A patent/TW491838B/zh not_active IP Right Cessation
- 1997-04-11 EP EP97920690A patent/EP0901470B1/de not_active Expired - Lifetime
- 1997-04-11 KR KR1019980709023A patent/KR100331217B1/ko not_active Expired - Fee Related
- 1997-04-11 WO PCT/EP1997/001882 patent/WO1997043260A1/en not_active Ceased
- 1997-04-11 DK DK97920690T patent/DK0901470T3/da active
- 1997-04-11 BR BR9709072A patent/BR9709072A/pt active Search and Examination
- 1997-04-11 AU AU26978/97A patent/AU717849B2/en not_active Ceased
- 1997-04-11 PT PT97920690T patent/PT901470E/pt unknown
- 1997-04-11 ES ES97920690T patent/ES2218675T3/es not_active Expired - Lifetime
- 1997-04-11 DE DE1997628392 patent/DE69728392T2/de not_active Expired - Fee Related
- 1997-04-11 JP JP54042397A patent/JP3245179B2/ja not_active Expired - Fee Related
- 1997-04-11 CN CN97194016A patent/CN1124262C/zh not_active Expired - Fee Related
- 1997-04-11 NZ NZ332640A patent/NZ332640A/en unknown
- 1997-04-11 IL IL12590397A patent/IL125903A0/xx unknown
- 1997-04-11 TR TR1998/02269T patent/TR199802269T2/xx unknown
- 1997-04-11 UA UA98115906A patent/UA50767C2/uk unknown
- 1997-04-11 CZ CZ19983582A patent/CZ292928B6/cs not_active IP Right Cessation
- 1997-04-11 PL PL97329725A patent/PL329725A1/xx unknown
- 1997-04-11 US US09/147,096 patent/US6017945A/en not_active Expired - Fee Related
- 1997-04-11 HU HU9901245A patent/HUP9901245A3/hu unknown
- 1997-04-11 AT AT97920690T patent/ATE263151T1/de not_active IP Right Cessation
- 1997-04-11 CA CA002253876A patent/CA2253876A1/en not_active Abandoned
- 1997-04-11 EA EA199800908A patent/EA001471B1/ru not_active IP Right Cessation
- 1997-04-11 SI SI9730646T patent/SI0901470T1/xx unknown
- 1997-04-11 SK SK1503-98A patent/SK150398A3/sk unknown
- 1997-04-29 HN HN1997000058A patent/HN1997000058A/es unknown
- 1997-05-02 PE PE1997000345A patent/PE65098A1/es not_active Application Discontinuation
- 1997-05-07 ID IDP971517A patent/ID16878A/id unknown
- 1997-05-07 CO CO97024471A patent/CO4650036A1/es unknown
- 1997-05-07 DZ DZ970074A patent/DZ2227A1/fr active
- 1997-05-07 AR ARP970101888A patent/AR007030A1/es not_active Application Discontinuation
- 1997-05-07 UY UY24546A patent/UY24546A1/es not_active IP Right Cessation
- 1997-05-07 TN TNTNSN97078A patent/TNSN97078A1/fr unknown
- 1997-05-07 MA MA24599A patent/MA26428A1/fr unknown
- 1997-05-08 ZA ZA973963A patent/ZA973963B/xx unknown
- 1997-05-08 AP APAP/P/1997/000982A patent/AP830A/en active
- 1997-05-09 HR HR970249A patent/HRP970249B1/xx not_active IP Right Cessation
1998
- 1998-08-28 IS IS4838A patent/IS1856B/is unknown
- 1998-10-09 OA OA9800192A patent/OA10896A/en unknown
- 1998-10-27 BG BG102873A patent/BG102873A/xx unknown
- 1998-11-09 NO NO19985225A patent/NO312547B1/no not_active IP Right Cessation
1999
- 1999-10-07 US US09/414,361 patent/US6136843A/en not_active Expired - Fee Related
2000
- 2000-04-24 US US09/556,651 patent/US6306852B1/en not_active Expired - Fee Related
2001
- 2001-01-09 US US09/756,835 patent/US6384070B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
AR007030A1 (es)	1999-10-13
ID16878A (id)	1997-11-20
TNSN97078A1 (fr)	2005-03-15
ATE263151T1 (de)	2004-04-15
ZA973963B (en)	1998-11-09
CN1124262C (zh)	2003-10-15
US6384070B2 (en)	2002-05-07
HRP970249B1 (en)	2003-06-30
HRP970249A2 (en)	1998-06-30
CZ358298A3 (cs)	1999-08-11
HUP9901245A2 (hu)	1999-08-30
KR100331217B1 (ko)	2002-05-09
EP0901470B1 (de)	2004-03-31
IL125903A0 (en)	1999-04-11
DE69728392T2 (de)	2005-01-13
HN1997000058A (es)	1997-06-26
HUP9901245A3 (en)	2002-01-28
CN1216531A (zh)	1999-05-12
EP0901470A1 (de)	1999-03-17
UY24546A1 (es)	2000-09-29
ES2218675T3 (es)	2004-11-16
OA10896A (en)	2001-10-11
EA199800908A1 (ru)	1999-06-24
IS4838A (is)	1998-08-28
US20010014677A1 (en)	2001-08-16
PL329725A1 (en)	1999-04-12
AU717849B2 (en)	2000-04-06
DE69728392D1 (de)	2004-05-06
HK1019149A1 (en)	2000-01-14
AU2697897A (en)	1997-12-05
KR20000010879A (ko)	2000-02-25
JP3245179B2 (ja)	2002-01-07
BG102873A (en)	1999-11-30
DZ2227A1 (fr)	2002-12-25
AP9700982A0 (en)	1997-07-31
AP830A (en)	2000-05-03
DK0901470T3 (da)	2004-07-12
CZ292928B6 (cs)	2004-01-14
MA26428A1 (fr)	2004-12-20
NO985225D0 (no)	1998-11-09
SI0901470T1 (en)	2004-08-31
CO4650036A1 (es)	1998-09-03
US6017945A (en)	2000-01-25
EA001471B1 (ru)	2001-04-23
NO312547B1 (no)	2002-05-27
TR199802269T2 (xx)	2001-12-21
PT901470E (pt)	2004-07-30
JPH11508285A (ja)	1999-07-21
TW491838B (en)	2002-06-21
PE65098A1 (es)	1998-10-29
IS1856B (is)	2003-02-21
US6306852B1 (en)	2001-10-23
WO1997043260A1 (en)	1997-11-20
UA50767C2 (uk)	2002-11-15
US6136843A (en)	2000-10-24
CA2253876A1 (en)	1997-11-20
BR9709072A (pt)	1999-08-03
GB9609641D0 (en)	1996-07-10
NO985225L (no)	1998-11-09
NZ332640A (en)	2001-03-30

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CZ13694A3 (en)	1994-07-13	Indoles, process of their preparation and pharmaceutical preparations based thereon
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