CZ219796A3 - Antagonists of endothelin receptor - Google Patents
Antagonists of endothelin receptor Download PDFInfo
- Publication number
- CZ219796A3 CZ219796A3 CZ962197A CZ219796A CZ219796A3 CZ 219796 A3 CZ219796 A3 CZ 219796A3 CZ 962197 A CZ962197 A CZ 962197A CZ 219796 A CZ219796 A CZ 219796A CZ 219796 A3 CZ219796 A3 CZ 219796A3
- Authority
- CZ
- Czechia
- Prior art keywords
- methoxyphenyl
- carboxymethyloxyphenyl
- carboxymethyloxy
- dimethoxyphenyl
- phenyl
- Prior art date
Links
- 102000010180 Endothelin receptor Human genes 0.000 title description 2
- 108050001739 Endothelin receptor Proteins 0.000 title description 2
- 239000005557 antagonist Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- -1 1H-tetrazol-5-yl Chemical group 0.000 claims description 2059
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 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 3
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 2
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- ACBOEIFVNPMNBV-UHFFFAOYSA-N 1-(1,3-benzodioxol-4-ylmethyl)-4-(4-methoxyphenyl)-2-oxo-[1]benzofuro[3,2-b]pyridine-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(C=1OC2=CC=CC=C2C=11)=C(C(O)=O)C(=O)N1CC1=CC=CC2=C1OCO2 ACBOEIFVNPMNBV-UHFFFAOYSA-N 0.000 claims 1
- NGBHXSHILGTLGO-UHFFFAOYSA-N 1-(1,3-benzodioxol-4-ylmethyl)-4-(4-methoxyphenyl)-7-methyl-2-oxo-[1]benzothiolo[3,2-b]pyridine-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(C=1SC2=CC(C)=CC=C2C=11)=C(C(O)=O)C(=O)N1CC1=CC=CC2=C1OCO2 NGBHXSHILGTLGO-UHFFFAOYSA-N 0.000 claims 1
- IXXAHTXVZZRGQT-UHFFFAOYSA-N 2-(2-methoxyphenoxy)-4-(4-methoxyphenyl)-[1]benzofuro[3,2-b]pyridine-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=C(C(O)=O)C(OC=2C(=CC=CC=2)OC)=NC2=C1OC1=CC=CC=C12 IXXAHTXVZZRGQT-UHFFFAOYSA-N 0.000 claims 1
- HKMCDWDDJXYYRK-UHFFFAOYSA-N 4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-[(2-methoxyphenyl)methyl]-2-oxo-[1]benzofuro[3,2-b]pyridine-3-carboxylic acid Chemical compound COC1=CC=CC=C1CN1C(=O)C(C(O)=O)=C(C=2C=C3OCCOC3=CC=2)C2=C1C1=CC=CC=C1O2 HKMCDWDDJXYYRK-UHFFFAOYSA-N 0.000 claims 1
- FCJOBOUPUCWGGT-UHFFFAOYSA-N 4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-[(2-methoxyphenyl)methyl]-3-(2h-tetrazol-5-yl)-[1]benzofuro[3,2-b]pyridin-2-one Chemical compound COC1=CC=CC=C1CN1C(=O)C(C=2NN=NN=2)=C(C=2C=C3OCCOC3=CC=2)C2=C1C1=CC=CC=C1O2 FCJOBOUPUCWGGT-UHFFFAOYSA-N 0.000 claims 1
- BBQVZZLPYFHCQZ-UHFFFAOYSA-N 4-(4-methoxyphenyl)-1-[(2-methoxyphenyl)methyl]-2-oxo-[1]benzofuro[3,2-b]pyridine-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(C1=C2C3=CC=CC=C3O1)=C(C(O)=O)C(=O)N2CC1=CC=CC=C1OC BBQVZZLPYFHCQZ-UHFFFAOYSA-N 0.000 claims 1
- KECPGAHGNZLNCC-UHFFFAOYSA-N 4-(4-methoxyphenyl)-2-[(2-methoxyphenyl)methoxy]-[1]benzofuro[3,2-b]pyridine-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=C(C(O)=O)C(OCC=2C(=CC=CC=2)OC)=NC2=C1OC1=CC=CC=C12 KECPGAHGNZLNCC-UHFFFAOYSA-N 0.000 claims 1
- 208000028257 Joubert syndrome with oculorenal defect Diseases 0.000 claims 1
- 150000001639 boron compounds Chemical class 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 102000002045 Endothelin Human genes 0.000 abstract description 2
- 108050009340 Endothelin Proteins 0.000 abstract description 2
- 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 abstract description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 70
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 66
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 65
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 64
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 63
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 62
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 61
- 239000011664 nicotinic acid Substances 0.000 description 49
- 125000004494 ethyl ester group Chemical group 0.000 description 43
- 238000006243 chemical reaction Methods 0.000 description 27
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 235000001968 nicotinic acid Nutrition 0.000 description 14
- 239000012442 inert solvent Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
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- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 6
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- 229910052784 alkaline earth metal Inorganic materials 0.000 description 6
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 5
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- 229910002027 silica gel Inorganic materials 0.000 description 5
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 description 4
- 125000006500 3-trifluoromethoxy benzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC(F)(F)F)=C1[H])C([H])([H])* 0.000 description 4
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- UODXCYZDMHPIJE-UHFFFAOYSA-N menthanol Chemical compound CC1CCC(C(C)(C)O)CC1 UODXCYZDMHPIJE-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- XBLVHTDFJBKJLG-UHFFFAOYSA-N nicotinic acid ethyl ester Natural products CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229910001950 potassium oxide Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical class [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- 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
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Antagonisty receptoru endothelinu
Oblast vynálezu
Vynález má řešit úkol nalézt nové sloučeniny a to zejména takové, kterých lze použít jako léčiv.
Vynález se týká sloučenin o vzorci I
,RZ kde níže uvedená označení mají příslušný význam
-Y-Z- -NR-C0-,-N31 C (OR7 )-nebo -N=CR8-, i
Ar,
R‘
C00R , CN, lH-tetrazol-5-yl nebo C0NHS02Ar,
R , R4, R5 vždy nezávisle na sobě Rc, 0R°, S(O)mRb, Hal
N02, NR°r6 NHCOR*? NHSO2R? OCOR6, C00R6nebo CN,
R6, R6'
R'
R{
Ar vždy nezávisle na sobě H, alkyl s 1 až 6 C-atomy, benzyl nebo fenyl (CH2)nAr,
Ar nebo OAr nesubstituovaný nebo jednou, dvakrát nebo třikrát R9, R^9nebo Rl^-substituovaný fenyl nebo nesubstituovaný naftyl nebo jedna nesubstituovaná nebo ve fenylové
-- · 9 1 η časti jednou nebo dvakrat R nebo R substituovaná
- skupina nebo nesubstituovaná nebo v cyklohexadienylovém dílu 9 10 jednou nebo dvakrát R nebo R substituovaná
E
D
Hal
X m
R9,R10, R11 vždy nezávisle na sobě R6, OR6, Hal, CFj, OCF3, ochf2,- och2f, no2, nr6r6~ nhcor6, cn, nhso2r6, coor6, COR6, CONHSO2Ar, O(CH2)nR2, O(CH2)n0R6nebo S(O)mR6, CH2, S nebo O, karbonyl nebo [c(R6R6)J n,
F, Cl, Br nebo I,
O nebo S,
0, 1 nebo 2 η 1 nebo 2, jakož i jejich solí.
Dosavadní stav techniky
Podobné sloučeniny s indanovými a indenovými jádry jsou známy z WO 93/ 08799, sloučeniny s indolsystémy pak z WO
94/14434, pyrimidinderiváty z EP 0 525 708 AI a fenyl a naftyl sloučeniny z EP 0 617001 AI.
Bylo shledáno, že sloučeniny podle vzorce I a jejich soli se dobře snášejí a vykazují velice cenné farmakologické vlastnosti. Mají zejména endothelin-receptorové antagonistické vlastnosti a mohou tedy sloužit k léčení nemocí jako je hypertonie, srdeční insuficience, koronární onemocnění srdce, renální, cerebrální a myokardinální ischemie, insuficience ledvin, mozkové příhody, subarachnoidální hemoragie, arteriosklerosa, pulmonální vysoký tlak, zánětlivá onemocnění, astma, hyperplaze prostaty, endotoxický šok a komplikace po podávání látek jako je např cyklosporin a další a u nemocí s působením endothelinu.
Sloučeniny vykazují mezi jiným vysokou afinitu k endothelin-subreceptorům ET a ET . Tyto účinky lze zjistit obvyklými metodami in vitro nebo in vivo, jak je např, popsáno
P.D.Steinem a kol., J.Med.Chem 37, 1994, 329-331 a E.Ohlsteinem a kol. Proč. Nati. Acad. Sci USA 91, 1994, 8052-8056.
Vhodná metoda ke stanovení účinku na pokles krevního tlaku je např. popsána M.K.Basilem a kol. J.Cardiovasc. Pharmacol, 22, 1993, 897-905 a J. Langen a kol., Lab. Animal 20, 1991, č. přihl.1016.
Sloučeniny o vzorci I lze použít jako účinné látky léčiv v humánní a veterinárně medicíně, zejména k profylaxi a/nebo léčení srdečních, oběhových a cévních onemocnění, především však hypertonie a srdeční insuficience.
Předmět vynálezu
Předmětem vynálezu jsou sloučeniny o vzorci I a jejich soli, jakož i způsob přípravy těchto sloučenin a jejich solí, vyznačený tím, že (a) pro přípravu sloučeniny podle vzorce I kde
-Y-Z- znamená -NR?-CO- nebo -N=C(OR 0- , se sloučenina o vzorci II kde
R1
r\
3 4=;
Rx Ο ώ U J O · Ό
Z f f f f a X mají významy definované v nároku 1 uvede do reakce se sloučeninou o vzorci III
R7-Q III kde
Q znamená Cl,Br,I nebo volnou nebo reakce schopnou funkční
OH-skupinu a
R má význam definovaný v nároku 1, nebo že se (b) pro přípravu sloučeniny o vzorci I, kde
-Y-Z- znamená -N=C(Ar)uvede do reakce sloučenina o vzorci IV
kde
Q znamená Cl,Br nebo I a r1, R^, r4, r5 a x mají význam definovaný v nároku 1, se sloučeninou o vzorci V
Ar-BLL' V kde
L,L'znamená vždy nezávisle na sobě OH,OCH3, OC2H5nebo OC3H7a Ar má význam udaný v nároku 1, nebo že se
c) pro přípravu sloučeniny o vzorci I kde
-Y-Z- znamená -N=C(OAr)-, uvede sloučenina o vzorci IV kde
Q znamená Cl,Br,I nebo reakce schopnou funkční OH skupinu do reakce se sloučeninou o vzorci VI
Ar-OH VI, a/nebo že se ve sloučenině o vzorci I jeden nebo více zbytků R^, R2, R2, R4a/nebo R^přemění na jeden nebo více zbytků R1, R2, R2, R4 a/nebo R^ , když se například
i) nitro skupina redukuje na amino skupinu, ii) ester skupina se hydrolysuje na karboxy skupinu, iii) amino akupina se redukční aminací přemění na alkylovaný amin, iv) karboxy skupina se přemění na sulfonamidokarbonyl skupinu a/nebo se zásada nebo kyselina o vzorci I přemění na jednu z jejich solí.
Pro všechny zbytky, které se několikrát vyskytují, jako např. R4a Ar platí, že jejich významy jsou na sobě navzájem nezávislé.
V uvedených vzorcích má alkyl 1 až 6 , s výhodou 1,2,3 nebo 4 C-atomy. Alkyl znamená především methyl, dále ethyl, propyl, isopropyl, butyl, isobutyl, sek.-butyl nebo tert.-butyl, dále také pentyl, 1-, 2- nebo 3-methylbutyl, 1,1-, 1,2-nebo 2.2-nebo
2.2- dimethylpropyl, 1-etnylpropyl, hexyl, 1-,2-,3- nebo
4-methylpěntyl, l/l-/ 1/2-, 1/3-, 2,2-, 2,3- nebo
3.3- dimethylbutyl, 1- nebo 2-ethylbutyl, 1-ethyl-l-methylpropyl, l-ethyl-2-methylpropyl, 1, 1,2-nebo 1,2,2-trimethylpropyl.
E znamená především 0¾ nebo 0, dále S.
D znamená především karbonyl a CH2.
X znamená s výhodou 0, dále se dává přednost S. m znamená zejména 0, dále s výhodou také 1 a 2. n je především 1, dále s výhodou 2.
Hal znamená především F, Cl nebo Br, ale také I.
Ar je nesubstituovaný, s výhodou - jak bylo již uvedeno monosubstituovaný fenyl,t.j. je s výhodou fenyl, o-, m- nebo p-tolyl, o- m- nebo p-ethylfenyl, o-,m- nebo p-propylfenyl, o-m- nebo p-isopropylfenyl, 0-, m- nebo p-tert-butylfenyl, o-,m- nebo p-trifluormethylfenyl, o-, m- nebo p-hydroxyfenyl, o-,m- nebo p—nitrofenyl, o-,m- nebo p-aminofenyl, o-,m- nebo p-(N-methylamino)-fenyl, 0-, m- nebo p-acetamidofenyl, o-,m- nebo p-(trifluoromethoxy)-fenyl, 0-, mnebo p-kyanfenyl, o-,m- nebo p-methoxyfenyl, o-, m- nebo p-ethoxyfenyl, o-,m- nebo p-karboxyfenyl , o-, m- nebo p-methoxykarbonylfenyl, o-,m- nebo p-ethoxykarbonylfenyl, o-, mnebo p-benzyloxykarbonylfenyl, o-, m- nebo p (karboxymethoxy)-fenyl, o-, m- nebo p-(methoxykarbonylmethyloxy)fenyl,o-,m- nebo p-(methoxykarbonyl-ethyloxy)-fenyl, o-,m- nebo p(Ν,Ν-dimethylamino)-fenyl, o-, m- nebo p- (N-ethylamino)-fenyl, o-, m- nebo p(Ν,Ν-diethylamino)-fenyl,o,m- nebo p-fluorfenyl, o-,m- nebo p-bromfenyl, o-,m-nebo p-chlorfenyl, o-,m- nebo p-(difluormethoxy)-fenyl, o-,m- nebo p-(fluormethoxy)-fenyl, o-, m- nebo p-formylfenyl, o-m- nebo p-acetylfenyl, o-, m- nebo p-propionylfenyl, o-, m- nebo p-butyrylfenyl, o-, m- nebo p-pentanoylfenyl, o-, m- nebo p-(fenylsulfoamidokarbonyl)-fenyl, o-, m- nebo p-f enoxyf enyl, o-, m- nebo p-methylthiof enyl, o-, πιnebo p-methylsulfinylfenyl, o-, m- nebo p-methylsulfonylfenyl, o-, m- nebo p-benzyloxyfenyl, o-, m- nebo p-kyanmethyloxyfenyl, dále se zde také upřednostňuje 2,3-methylendioxyfenyl,
3.4- methylendioxyfenyl,2,3-ethylendioxyfenyl,3,4-ethylendioxyfenyl,
2,3-oxo-methylendioxy)fenyl 2,3, 2,4- 2,5-, 2,6-, 3,4- nebo
3.5- (difluormethoxy)-(karboxymethyloxy)-fenyl, 2,3-, 2,4- 2,5-,
2.6- , 3,4- nebo 3,5-methoxy-(karboxymethyloxy)-fenyl, 2,3-, 2,42,5-, 2,6-, 3,4- nebo 3,5-hydroxy-(karboxymethyloxy)-fenyl.
Ar znamená dále s výhodou 2,3-dihydrobenzofuranyl
2.3- dihydro-2-oxo-furanyl, 1,3-dithiaindanyl
2.1.3- benzothiadiozolyl, 2,1,3-benzoxadiazolyl, dále pak 2,32,4-, 2,5-, 2,6-, 3,4- nebo 3,5-difluorfenyl,
2,6-, 3,4- nebo 3,5-.dicnlorfenyl, 2,3-, 2,4-,
2,3-2,4-, 2,5-, 2,5-, 2,5-, 3,4· nebo 3,5-dibromfenyl, -2-chlor-5-methyl-,
2- methyl-4-chlor-',
3- chlor-4-methyl, 2-brom-3-methyl, 2-brom-6-methyl,
2-chlor-3-methyl-,2-chlor-4-methyl,
2-chlor-6-methyl, 2-methyl-5-chlor, 3-chlor-5-methyl nebo 2-brom-4-methyl, 3-brom-4-methyl,
2-methyl-3-chlor, 2-methyl-6-chlor,
3-methyl-4-chlorfenyl, 2-brom-5-methyl,
3-brom-5-methyl nebo
3-methyl-4-bromfenyl, 2,4-nebo 2,5-dinitrofenyl, 2,5-nebo 3,4-dimethoxyfenyl, 3-nitro-4-chlorfenyl, 2-amino-3-chlor,
2-amino-4-chlor, 2-amino-5-chlor-nebo 2-amino-6-chlorfenyl,
2- nitro-4-N,N-dimethylamino- nebo
3- nitro-4-N,N-dimethylaroinofenyl, 3-karboxy-2-methoxy-,
3-karboxy-4-methoxy-nebo 3-karboxy-5-methoxyfenyl, 2,3,4,-,
2,3,5-, 2,3,6-, 2,4,6-, nebo 3,4,5-trichlorfenyl,
2,4,6-tri-tert.butylfenyl, dále s výhodou
2-nitro-4-(trifluormethyl)fenyl, 3,5-Di-(trifluormethyl)-fenyl,
2,5-dimethylfenyl, 2-hydroxy-3,5-dichlorfenyl, 2-fluor-5 nebo
4-fluor-3-(trifluormethyl)-fenyl, 4-chlor-2- nebo 4-chlor-3(trifluomethyl, 2-chlor-4-nebo 2-chlor-5-(trifluormethyl)fenyl, 4-brom-2-nebo 4-brom-3-(trifluormethyl)-fenyl, p-lodfenyl, 2-nitro-4-methoxyfenyl, 2,5-dimethoxy-4-nitrofenyl,3,5-dikarboxyfenyl, 2-chlor-3-nitro-5-karboxy-fenyl, 4-chlor-3-carboxyfenyl, 2-methyl-5-nitrofenyl,2,4-dimethyl-3-nitrofenyl, 3,6-dichlor-4-4-aminofenyl,4-fluor-3-chlorfenyl, 4-fluor-3-chlorfenyl,
4-fluor-3,5-dimethylfenyl, 2-fluor-4-bromfenyl, 2,5-difluor-bromfenyl, 2,4-dichlor-5-methylfenyl, 3-brom-6-methoxyfenyl, 3-chlor6-methoxyfeny1, 3-chlor-4-acetamidofenyl, 4-hydroxy-3-karboxy fenyl,2-methoxy-5-methylfenyl nebo 2,4,6-triisopropylfenyl, dále naftyl.
Zbytek R? znamená především karbomethoxy, karboethoxy, karbopropoxy, karbobutoxy, karbobenzyloxy, dále kyan, l-H-tetrazol-5-yl nebo fenylasulfoamidokarbonyl, zejména pak karboxy skupiny.
Zbytky , R^a R^ znamenají vždy nezávisle na sobě především H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sek.-butyl nebo tert.-butyl, benzvl, F,Cl,Br, methoxy, ethoxy, fenoxy, benzyloxy, nitro nebo kyan, dále se upřednostňuje amino, methylamino, dimethylamino, ethylamino, diethylamino, acetylamino, propionylamino, butyrylamino, methylsulfonamido, ethylsulfonamido, fenylsulfonamido, methylkarbonyloxy, fenylkarbonyloxy, methyloxykarbonyl, ethyloxykarbonyl, methylthio, ethylthio, propylthio, methylsulfinyl, ethylsulfinyl, fenylsulfinyl, methylsulfonyl, ethylsulfonyl nebo i fenylsulfonyl.
Sloučeniny o vzorci I mohou mít jedno nebo několik chirálních center a proto se mohou vyskytovat v ruyných stereoisomerních formách. Vzorec I zahrnuje všechny tyto formy.
S ohledem na výše uvedené jsou předmětem vynálezu zejména takové sloučeniny podle vzorce I, ve kterých nejméně jeden z uvedených zbytků má výše uvedený význam, kterému se dává přednost Přednostní skupiny sloučenin mohou být charakterizovány následujícími dílčími vzorci Ia až Ig, které odpovídají vzorci
| I a kde vzorci I | nikoli blíže označené zbytky, mají udaný význam, znamenají | |||
| v | Ia | -Y-Z- | znamená | -NR7-CO |
| v | lb | -Y-Z- | znamená | N=CR8, |
| v | Ic | -Y-Z | znamená | nr7-co |
| X | znamená | 0, | ||
| v | Id | -Y-Z- | znamená | nr7-co, |
| X | znamená | 0 nebo | ||
| Ar | znamená | skupinu | ||
| v | Ie | -v-Z- | znamená | -N=CR8, |
| R8 | znamená | Ar, | ||
| Ar | znamená | jednou, < | ||
| R9, R10 | nebo rH | |||
| X | znamená | 0, | ||
| v | If | X | znamená | S, |
v Ig
-Y-ZR7
Ar
-Y-Z·
X
Ar
R8 znamená NR7-COznamená Cí^Ar a znamená skupinu znamená N=Cr8znamená O znamená skupinu znamená OAr .
Sloučeniny podle vzorce I a také výchozí látky k jejich přípravě se ostatně připravují podle známých metod, které jsou popsány ( např. ve standartních dílech jako jsou Houben-Weyl, Metody organické chemie, Georg-Thieme Verlag, Stuttgart, zejména však ve WO 94/14434) a sice za reakčních podmínek, které jsou pro uvedené reakce známé a vhodné. Přitom je tedy možno využít o sobě známé, zde blíže nezmiňované varianty oříoravv.
Pokud je to žádoucí, lze rovněž výchozí látky vytvořit in sítu, takže se z reakční směsi neeliminuji, ale dále přecházejí na sloučeniny podle vzorce I.
Sloučeniny podle vzorce I lze s výhodou připravit tím, že se uvedou do reakce sloučeniny podle vzorce II se sloučeninami podle vzorce III.
Ve sloučeninách podle vzorce III znamená Q především Cl, Br, I nebo reakce schopnou odloučenou skupinu OH jako alkylsulfonyloxy s 1 - 6 atomy C ( dává se přednost methylsulfonyloxy skupině ) nebo arylsulfonyloxy s 6-10 atomy C (dává se přednost fenyl- nebo p-tolylsulfonyloxy skupině ) .
Reakce probíhá obvykle v inertním rozpouštědle, za přítomnosti prostředku, který váže kyselinu, zejména hydroxidů uhličitanů nebo hydrouhličitanů alkalických kovů nebo alkalických zemin nebo jiné soli slabé kyseliny alkalických kovů hebo alkalických zemin, především draslíku,sodíku, vápníku,nebo cesia Také přídavek organické báze jako triethylamin, dimethylamin, pyridin nebo chinolin nebo přebytku amidových složek podle vzorce II resp. alkylačních derivátů podle vzorce III může reakci příznivě ovlivnit. Reakční doba se pohybuje mezi několika minutami a 14 dny podle příslušných podmínek, reakční teplota pak mezi C/až 1501’ C, normálně mezi 20° až 130’ C .
Jako inertní rozpouštědlo se hodí např. uhlovodíky jako hexan, petroléter, benzol, toluol nebo xylol , chlorované uhlovodíky jako trichlorethylen, 1,2-dichlorthan, tetrachlor, chloroform nebo dichlormethan, alkoholy jako methanol, ethanol, isopropanol, n-propanol, n-butanol nebo tert. butanol, éter jako diethyléter, isopropyléter, tetrahydrofuran (THF) nebo dioxan, gykoléter jako ethylenglykomonomethyl-nebo -monoethyléter (methylglvkol nebo ethylglykol ), ethylenglykoldimethyléter (diglymy ) , ketony jako aceton nebo butanon, amidy jako acetamid, dimethylacetamid nebo dimethylformamid (DMF), nitrily jako acetonitril, sulfoxidy jako dimethylsulfoxid (DMSO), sirouhlík, kyseliny karboxylové jako kyselina mravenčí nebo kyselina octová, nitro sloučeniny jako nitromethan nebo nitrobenzol, ester jako ethylacetát nebo směsi uvedených rozpouštědel.
Výchozí sloučeniny podle vzorce II jsou obvykle nové, lze je však podle známých metod připravit. Tak je možno připravit např.ethylester 1,2-dihydro-4-(methoxyfenyl)-2-oxo-benzofuro (3,2-b) pyridin-3-kyseliny karboxylové z 3-amino-2-(4-methoxybenzoyl)-benzofuranu a diethylesteru kyseliny malonové bez nebo za přítomnosti inertního rozpouštědla. Tato reakce probíhá při teplotách mezi 0 a asi 200° C , s výhodou se pracuje mezi 30 až 80* C.
Jako inertní rozpouštědla se hodí rozpouštědla výše uváděná.
Sloučeniny podle vzorce I lze dále ještě připravit tak, že se uvedou do reakce sloučeniny podle vzorce IV se sloučeninami podle vzorce V.
Ve sloučeninách podle vzorce IV znamená Q především Cl nebo Br, ale také I.
Ve sloučeninách podle vzorce V znamená L a I? především vždy nezávisle na sobě OH, methoxy, ethoxy, propoxy nebo iso-propoxy skupinu.
Reakce probíhá obvykle v inertním rozpouštědle za přítomnosti báze a katalyzátoru z ušlechtilého kovu.
Reakčni doba se pohybuje podle aplikovaných podmínek mezi několika minutami a 14 dny, reakčni teplota pak mezi o’a 15(/, normálně mezi 20*32 13O3C.
Jako inertní rozpouštědla a báze lze využít již výše uváděná
Jako katalyzátory z ušlechtilých kovů lze použít zejména palladium-(0)-kytalyzátory jako tetrakis (trifenylfosfin)palladium-(0) .
Výchozí sloučeniny vzorce IV jsou obvykle nové. Lze je však připravit podle známých metod.Tak je možno připravit např.ethyl ester 2-chlor-4-(4-methoxyfenyl)-benzofuro(3,2-b)pyridin-3kyseliny karboxylové z ethylesteru 1,2 dihydro-4-(4-methoxyfenyl)
2-oxobenzo-furo (3,2-b)pyridin-3-kyseliny karboxylové s POC1 . Tato reakce probíhá za teplot mezi O až 200° , s výhodou se pracuje mezi 30* až 80° C.
Sloučeniny podle vzorce I se mohou také připravit tím, že se uvedou do reakce sloučeniny podle vzorce IV se sloučeninami o vzorci VI.
Ve sloučeninách podle vzorce IV znamená Q především Cl,Br,I nebo reakce schopnou odloučenou OH skupinu.
Reakce obvykle probíhá v inertním rozpouštědle a za přídavku jedné z výše uvedených bází.
Dále je také možno sloučeninu podle vzorce I převést na jinou sloučeninu podle vzorce I, jestliže jeden nebo více zbytků R-3, R-^a/nebo R^převedeme na jeden nebo více jiných zbytků R1, R2 , R3, R'4, a/nebo R-5, když se nitroskupiny redukují na aminoskupiny např.hydrogenací na Raney-niklu nebo Pd-uhlí v inertním rozpouštědle jako je menthanol nebo ethanol a/nebo se esterová skupina převede na karboxylovou skupinu a/nebo se aminoskupina převede redukční aminací na alkylovaný amin a/nebo se karboxyskupina esterifikuje reakcí s alkoholy.
Dále je možno volné amino skupiny obvyklým způsobem acylovat chloridem nebo anhydridem kyseliny nebo alkylovat nesubstituovaným nebo substituovaným alkyhalogenidem, nejlépe v inertním rozpouštědle jako je dichlormethan nebo THF a/ nebo za přítomnosti báze jako je triethylamin nebo pyridin při teplotách mezi -60 až+30* C.
Podle potřeby je možno ve sloučenině podle vzorce I jednu funkčně obměněnou amino - u/nebo hydroxyskupinu solvolýzou nebo hydrogenolýzou podle obvyklých metod odloučit. Tak je možno např. sloučeninui podle vzorce I, která obsahuje skupinu NHCOOR - nebo skupinu COOR- - , převést na odpovídající sloučeninu podle vzorce I, která namísto těchto skupin bude obsahovat skupinu NH. - nebo HOOC. COOR' skupiny mohou být např. zmýdelněny NaOH nebo KOH ve vodě, vodě-THF nebo vodě-dioxanu při teplotách mezi 0 až 100® C .
Bázi sloučeniny podle vzorce I je možno kyselinou převést na odpovídající adiční sůl kyseliny, např. reakcí ekvivalentního množství báze a kyseliny v inertním rozpouštědle jako je ethanol a následným odpařením. Pro tuto přeměnu přicházejí v úvahu zejména kyseliny, která poskytují fyziologicky nezávadné soli. Je možno použít anorganické kyseliny jako např. kyselinu sírovou, dusičnou, halogenkyseliny jako kyselina chlorovodíková nebo bromovodíková, kyseliny fosforečné jako kyselina orthofosforečná, kyselina sulfaminová, dále organické kyseliny, zejména pak alifatické, alicyklické, aralifatické, aromatické nebo heterocyklické jedno- nebo vícebazické kyseliny karboxylové, sulfonové nebo sírové, např. kyselina mravenčí, octová, propionová, pivalinová, diethyloctová, malonová, jantarová, pimelinová, fumarová, maleinová, mléčná, vinná, jablečná, citrónová, glukonová, ascorbová, nikotinová, isonikotinová, methan - a ethansulfonová, ethandisulfonová, 2-hydroxyethansulfonová, benzolsulfonová, p-toluiosulfonová, naphtalin-mono- a disulfonová13
I laurylsírová. Soli fyziologicky závadných kyselin např. pikráty lze využít k izolaci a/nebo vyčištění sloučenin podle vzorce I.
Na druhé straně se mohou sloučeniny podle vzorce I s bázemi ( např. oxidy nebo uhličitany draslíku nebo sodíku) převést na odpovídající soli kovů, zejména alkalických kovů- nebo kovů alkalických zemin nebo na soli ammonia.
Dále je předmětem vynálezu použití sloučenin podle vzorce I a/nebo jejich fyziologicky ezávadných solí k přípravě farmaceutických přípravků, zejména nechemickou cestou. Sloučeniny je možno upravit spolu s nejméně jednou pevnou, tekutou a/nebo polotekutou pomocnou nebo nosnou látkou a případně v kombinaci s další nebo dalšími účinnými látkami do vhodné dávkovači formy.
Předmětem vynálezu jsou dále farmaceutické přípravky, které obsahují nejméně jednu sloučeninu podle vzorce I a/nebo jednu z jejich fyziologicky nezávadných solí.
Tyto přípravky lze použít jako léčiva v humánní nebo veterinární medicíně. Jako nosné látky přicházejí v úvahu organické a anorganické substance, které jsou vhodné pro enterální( např. orální ), parenterální nebo topickou aplikaci a nereagují s novými sloučeninami., např. voda, rostlinné oleje, benzylalkoholy, alkylenglykoly, polyethylenglykoly, glycerintriacetát, želatina, uhlovodíky jako laktosa nebo škrob, magnesiumstearát, talk, vazelína. Pro orální použití jsou vhodné zejména teblety, pilulky, dražé, kapsle, prášek, granulát, sirup, stávy nebo kapky, pro rektální užití čípky, pro parenterální aplikaci roztoky, především olejové nebo vodné roztoky, suspense, emulse nebo implantáty, pro topickou aplikaci masti, krémy a pudry. Nové sloučeniny lze rovněž lyofilizovat nebo dosažené lyofilizáty používat např. pro přípravu injekčních preparátů. Udané přípravky lze sterilizovat, mohou také obsahovat pomocné látky jako konzervační, stabilizační a/nebo zesitující prostředky,emulgátory, soli pro ovlivnění osmotického tlaku, pufry, barviva, příchuti a/nebo i další účinné látky, např. jeden nebo více vitaminů .
Sloučeniny podle vzorce I a jejich fyziologicky nezávadné soli mohou být využívány při léčení nemocí, zejména hypertonie a insuficience srdeční.
Pro tyto účely se připravují látky podle vynálezu v dávkovaní mezi 1 až 500 mg, zejména mezi 5 a 100 mg na jednu dávkovači jednotku. Denní dávka se především pohybuje v závislosti na kilogramu váhy pacienta od 0,002 až 10 mg. Specielní dávkování pro každého pacienta závisí totiž na nejrůznějších faktorech, např.na účinnosti specielního nasazení sloučeniny, na stáří, na tělesné váze, na všeobecném zdravotním stavu, pohlaví, na stravě, na době a způsobu podávání, na rychlosti vylučování, na kombinaci léčiv a závažnosti přéslušného onemocnění, pro které je léčení určeno. Dává se přednost orální aplikaci.
V textu přihlášky jsou teploty udávány ve stupních. Celsia,, bod tání •je označován F .' V následujících příkladech znamená obvyklé zpracování - přidá se voda, pokud je zapotřebí, upraví se pH podle konstituce konečného produktu mezi 2 až 10, extrahuje se ethylacetátem nebo dichlormethanem, odloučí se, vysuší se organická fáze nad síranem sodným, odpaří se a vyčistí se chromatografií na silikagelu, při čemž dojde také k odloučení dále popsaných isomerů a/nebo se nechá látka vykrystalizovat.
- hodnoty na silikagelu, eluát - ethylacetát /methanol 9:1,
Rfg- hodnoty na silikagelu, eluát : toluol/methyl-tert-butylether 1 : 1 -Rfc- hodnoty na silikagelu, eluát - petrolether /octan : 1, - Rfg - hodnoty na silikagelu, eluát methyl-tert.butyléter/petroléter 1:1.
Příklad 1
K roztoku 2,0 g ethylesteru 4-(l,4-benzodioxan-6-yl)-l,2-dihydro-2-oxobenzofuro(3,2-b)pyridin-3-kyseliny karboxylové (možno připravit reakcí s 3-amino-2-(l,4-benzodioxan-6-karbonyl)-benzofuranu a diethylmalonátu v acetonu a uhličitanu draselném, F.255° ,
3-amino-2-(l,4-benzohydroxybenzonitrilu a 6-bromacetyl1,4-benzodioxanu, F. 157°) v 15 ml DMF a 2,5 g uhličitanu česného se přidá 50% roztok 1,8 g 2-methoxybenzylchloridu (A) v dichlormethanuu. Reakční směs se 10 hodin míchá a zpracuje jako obvyle. Dostaneme N produkt alkylace - ethylester 4-(1,4-benzodioxan-6-yl) -1,2-dihydro-l- (2-methoxybenzyl) -2-oxo-benzof uro (3,2-b)pyridin-3-kyseliny karboxylové, F, 105° C a O produkt alkylace - ethylester 4-(l,4-benzodioxan-6-yl)-2-(2-methoxy-ben-
o
-15zyloxy)-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové,F. 166°.
Analogicky obdržíme z následujících ethylesterú 4-T-l,2dihydro-2-oxo-benzofuro (3,2-b}-pyridin-3-kyseliny karboxylové, kde T znamená fenyl, F. 2930 naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxoi-5-yl, F.2460
2- methoxyfenyl, F.19 20
3- methoxyfenyl, F.18 6’
4- methoxyfenyl, F.247’
2.3- dimethoxyíenyl
2.4- dimethoxyíenyl, F.22OC'
2.5- dimethoxyfenyl, F.2170'
3.4- dimethoxyřenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethcxyfenyl
3- difluormethoxyfenyl
4- difluormethcxyfenyl, F. 208^
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl, F. 208^
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl, F.1663
4-ethoxyfenyl, F. 2230
4-díetylaminofenyl F. 24412
4-methylthiofenyl, F.2280
3-fluor-4-methoxyfenyl, F.266°
2,3-dihydro-5-benzofuryl, F.2680
4-methylfenyl, F. 246°
2- ethoxy-5-methoxyfenyl, F. >300ύ
2,1,3-benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, s A následující ethylestery 4-T-l,2-dihydro-l-(2-methoxybenzyl) -2-oxobenzofuroC3,2-b]-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl, Rig 0,55
2- methoxyfenyl, Rfc 0,39
3- methoxyfenyl, R^0,51
4- methoxyfenyl, F.1097
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoixyfenyl
2- karboxymethyloxyfenyl
3- kaborxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- dif luormethoxyf enyl, F.222
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymetyhloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl, R%0,50
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl, R.f^ 0,37
2,3 dihydro-5-benzofuryl, R^0,36
4- methylfenyl
2- ethoxy-5-methoxyfenyl, R%0,41
2,1,3-benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl zrovna tak jako následující ethylestery 4-T-2-(2-methoxybenzyl oxy)-benzofuroC3,2-bj-pyridin-3-kyseliny karboxylová , kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl, F.1460
2- methoxyfenyl, F.1810
3- methoxyfenyl, F.108?
4- methoxyfenyl, Ρ.141σ
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl, Rf^ 0,7 5
2.5- dimethoxyfenyl, F.1210
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl, F.100°
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-feny1
2-karboxymethyloxy-3-methoxy-feny1
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymetyhloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4-trifluormethoxyfenyl, F 180
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl, F.102
4-metyhlthiofenyl, F.1880
3- fluor-4-methoxyfenyl, F.176
2.3- dihydro-5-benzofuryl, F. 140
4- methylfenyl, F.126
2- ethoxy-5-methoxyfenyl, F 109°
2.1.3- benzothiadiazol-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl .
Analogicky obdržíme reakcí 3-methoxybenzylchloridu s následujícími ethylestery 4-T-l,2-dihydro-2-oxo-benzofuro ¢3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl,
3- methoxyfenyl
4- methoxyfenyl,F.247°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- diemthoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- barboxymethyloxyfenyl
2- di fluormethoxyfenyl
3- di fluormethoxyfenyl
4- d i fluormethoxyfenyl
2-methoxy-3-karboxymethoxy-fenyl
2-methoxy-4-karboxymetyhloxy-fenyl
2-karboxymetyhloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
- 19 2-difluormethoxy-3-karboxymetyhloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymetyhloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3,4,5 -trimethoxyfeny1
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, následující ethylestery 4-T-l,2-dihydro-l-(3-methoxybenzyl) 2-oxo-benzofuroC3,2-b}-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
1- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F.1040,
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymetyhloxyf enyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- di fluormethoxyfenyl
4- di fluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-merhoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, jakož i následující ethylestery 4-T-2-(3-methoxybenzyloxy) benzofuroC3,2-bO-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F.lOó4’
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
- 2P
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymetzhyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methopxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiasdiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyf enyl
2-fluor-4-methoxyfenyl .
Analogicky dostaneme reakcí 4-methoxybenzylchloridu s následujícími ethylestery 4-T-l,2-dihydro-2-oxo-benzofuro C3,2-b3-pyridin-3- kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl '
1.4- benzodioxan-5-yl
1.3- benzodioxan-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F. 2470
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4-karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluornethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboixymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-feny1
2-difluormethoxy-3.-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenmyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-díethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, i následující ethylestery 4-T-l,2-dihydro-l-(4-methoxybenzyl)-2-oxobenzoíuro£3,2-bj-pyridin-3-kyseliny karboxylové kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F.1920
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, jakož i následující ethylestery 4-T-2-(4-methoxybenzyloxy) benzofuroC3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-6-yl
1, -4benzodioxan-5-yl
1.3- benzodioxan-4-yl
1.3- benzcdioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F.IOS^
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-di fluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl.
Analogicky připravíme reakcí 3,4-methylendioxybenzylchloridu s následujícími ethylestery 4-T-l,2-dihydro-2-oxo-benzofuro C3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená f enyl naftyl
1.4- benzcdioxan-6-yl.
1.4- benzcdioxan-5-yl
1.3- benzcdioxol-4-yl
1.3- benzcdioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,F.247°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimenhoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- dif luomethoxyf enyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl , následující ethylestery 4-T-l,2-dihydro-l-(3,4-methylendioxybenzyl) -2-oxobenzofuro f3,2-bjpyridin-3-kyseliny karbo xylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,F.177*
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-f enyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-di fluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl 2-trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trif1uormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-nethoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, jakož i následující ethylestery 4-T-2-(3,4-methylendioxybenzyl oxy)-benzofuro£3,2-bj-pyridin-3-kyselimy karboxylové,kde T znamená f enyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyf enyl
3- methoxyfenyl
4- methoxyfenyl,F.124°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyf enyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2,3-dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2,1, 3-benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl.
Analogicky obdržíme reakcí 2-karboxymethyloxy-4-methoxybenzylchloridu s následujícími ethylestery 4-T-l,2-dihydro-2oxobenzofuroC3,2-bj-pyridin-3-kyseliny karboxylová, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyf enyl
-methoxyf eny 1, F. 2 4
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2-karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- di fluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-feny1
2-karboxymethyloxy-3-methoxy-feny1
2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, tyto ethylestery 4-T-l,2-dihydro-(2-karboxymethyloxy-4-methoxy benzyl)-2-oxo-benzofuro¢3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4-methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-feny1
2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-feny1 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyf enyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl , jakož i následující ethylestery 4-T-2-(2-karboxymethyloxy-4-methoxy-benzyloxy)-benzofuroC3,2-bJ-pyridin-3-kyseliny karboxylové kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
-me thoxy f enyl, F. 10 2°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormetnoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-feny1
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormenhoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl .
Analogicky obdržíme reakcí 2,3-methylendioxybenzylchloridu s následujícími ethylestery 4-T-l,2-dihydro-2-oxo-benzofuro f3,2-b}-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,F.247*
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-feny1
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-feny1 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2-ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3-chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl následující ethylestery 4-T-l,2-dihydro-l-(2,3-methylendioxy benzyl)-2-oxobenzofuroζ3,2-bJ -pyridin-3-kyselxny karboxylová, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,Rfc 0,41
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-feny1
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- tri fluormethoxyf enyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyf enyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, jakož i následující ethylestery 4-T-2-(2,3-methylendioxybenzyloxy)-benzofurof3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,F.184°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-feny1 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl.
Analogicky připravíme reakcí 2-methylthiobenzylchloridu s následujícími ethylestery 4-T-l, 2-dihydro-2-oxo-benzofuroC3,2-bG) -pyridin-3-kyseliny karboxylové , kde T znamená fenyl naftyl
1.4- benzcdioxan-6-yl
1.4- benzcdioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzcdioxol-5-yl
2- methoxyfenyl
3- methoxyf enyl
4- methoxyfenyl,F.2477
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyf enyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-feny1 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfeny1
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-nethoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, jakož i následující ethylestery 4-T-l,2-dihydro-l-(2-methylthio benzyl)-2-oxobenzofuroC3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,Rfc0,3
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4-difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihvdro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, jakož i následující ethylestery 4-T-2-(2-methylthiobenzyloxy) benzofuroC3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
-methoxyf enyl, F. 12 2’
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3,4-dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormeuhoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethcxyfenyl
4-ethoxyfenyl
4-diethylamir.of enyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfeny1
2.1.3- benzothíadiazol-5-yl
2.4.5- trimethcxyfenyl
3- chlor-4-menhoxyfenyl
2-fluor-4-methoxyfenyl.
Analogicky obdržíme reakcí s 2,3-dimethoxybenzylchloridu s následujícími ethylestery 4-T-l,2-dihydro-2-oxo-benzofuro C3,2-b^pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyf enyl
4- methoxyfenyl,F.247°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyf enyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4—methylehiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl následující ethylestery 4-T-l,2-dihydro-l-(2,3-dimethoxybenzyl) 2-oxo-benzofurof3,2-bJ-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
-methoxy f enyl, F. 16 6*
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormeuhoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, jakož i následující ethylestery 4-T-2-(2,3-dimethoxybenzyloxy) benzofuroC3,2-bQ -pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl·, F.121°
2.3- dimeuhoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyf enyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyIoxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethoxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2,3-dihydro-5-benzofuryl
4- methylfenyl
2-ethoxy-5-methoxyfenyl
2,1,3-benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3-chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl.
Analogicky dostaneme reakcí 2,5-dimethoxybenzylchloridu s následuj ícími ethylestery 4-T-l,2-dihydro-2-oxo-benzofuroC3,2-bO pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzcdioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F. 24713
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, následující etyhlestery 4-T-l,2-dihydro-l-(2,5-dimethoxybenzyl)
2-oxobenzof uro (3,2-b}-pyridin-3-karboxylové kyseliny, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl ,Rf·. 0,42
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,Rfc 0,37
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl, Rf^ 0,35
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl, F.1550
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl, jakož i následující ethylestery 4-T-2-(2,5-dimethoxybenzyloxy) benzofuroC3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl, F.1450
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F.114°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyf eny1
2- difluormethoxyfenyl
3- difluormethoxyf enyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyf eny1
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl, F.96*'
4-diethylaminofenyl
4-methylthíofenyl
3- f luor-4-methoxyf enyl, F.136”
2.3- dihydrc-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl.
Analogicky dostaneme reakcí s 2,1,3-benzothiadiazol-5methylchloridem s následujícími ethylestery 4-T-l,2-dihydro 2-oxo-benzofuroC3,1-b}-pyridin-3-kyseliny karboxylová, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyf enyl, F. 247°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl 2-karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyf eny1
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- ber.zothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-mechoxyfenyl následující ethylesnery 4-T-l,2-dihydro-l-(23,1,3-benzothiazol5-methyl)-2-cxo-benzofuro(^3,2-bQ-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4-methoxyf enyl ,F. 221p
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormetzhoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethcxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-meťnoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfeny
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl jakož i následující ethylestery 4-T-2-(2,l,3-benzothiadiazol
5- methyloxy)-benzofuro(5,2-bJ-pyridin-3-kyseliny karboxylové kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyf enyl
4- methoxyfenyl,F. 183&
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl .
Analogicky obdržíme reakcí 3,4 methylendioxy-6-chlorbenzyl chloridu s 4-T-l,2-dihydro-2-oxo-benzofuroC3,2-bj-pyridin. -3-ky seliny karboxylové, kde T znamená fenyl naftyl
1, 4-benzodioxan-6-yl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,F.247°
2.3- dinetnoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karbcxymethyloxy-4-methcxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karbcxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2,3-dihydro-5-benzofuryl
4- methylfenyl
2-ethoxy-5-methoxyfenyl
2,1,3-benzothiadiazol-5~yl
2,4,5-trimethoxyfenyl
3-chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl následující ethylestery 4-T-l,2-dihydro-l-(3,4-methylendioxy6-chlor-benzyl)-2-oxo-benzofuroC3,2-bj-pyridin-3-kyseliny karboxylové , kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1, 3-benzodioxcl-4-yl
1.3- benzcdioxcl-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,Rfo 0,67
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2-karboxymethyloxyfenyl
- k a r b o x ym e t h y1oxyfeny1
4-karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-f eny1 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- tri f1uorme thoxyfeny1
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl 4-ethoxyfenyl 4-diethylaminofenyl 4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl jakož i následující etyhlestery 4-T-2-(3,4-methylendioxy-6chlor-benzylcxy)-benzofuro(3,2-bQ-pyridin-3-kyseliny karboxy lové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzcdioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyf enyl, F. 167°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethyloxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxyme thyloxy-4-methoxy-feny1
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-di fluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethcxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl.
Analogicky dostaneme reakcí 2-methoxybenzylchloridu s násle dujícími ethylestery 4-T-l,2-dihydro-2-oxo-7-methyl-benzofuro Q3,2-bj-pyridin-3-kyseliny karboxylová, kde T znamená fenyl nafryl
1.4- benzodiox=r-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfeny1
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4-difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl·
2- ethoxy-5-me~hoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl následuj ící enhylestery 4-T-l,2-dihydro-l-(2-methoxybenzyl)-2-oxo -7-methylbenzcfurof3,2-b}-pyridin-3-kyseliny karboxylové, kde i znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyf enyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3,4-dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl jakož i následující 4-T-2-(2-methoxybenzyloxy)-7-methylbenzo fůro£3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl 2-methoxyfenyl
3- methoxyfeny1
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethvloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl .
Analogicky obdržíme reakcí 2-methoxybenzylchloridu s ethylestery 4-T-l,2-dihydro-2-oxo-benzothieno(3,2-b)-pyridin-3 kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyf enyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- di f1uorme thoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormemhoxyfenyl
4- urifluormethoxyfenyl
4-trifluormemhoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl následuj ící ethylestery 4-T-l,2-dihydro-l-(2-methoxybenzyl)-2-oxo benzothieno C3,2-b}-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1.4- benzodioxan-6-yl
1.4- benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2,3-dihydro-5-benzofuryl
4- methylfenyl
2-ethoxy-5-methoxyfenyl
2,1,3-benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3-chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl , jakož i následující ethylestery 4-T-2-(2-methoxybenzyloxy)-benzo thieno£3,2-b]-pyridin-3-kyseliny karboxylová, kde T znamená fenyl naftyl
1.4- benzdioxan-6-yl
1.4- benzdioxan-5-yl
1.3- benzdioxol-4-yl
1.3- benzdioxci-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyf enyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl.
Příklad 2
Roztok 0,5 g ethylesteru 4-(l-4-benzodixoan-6-yl)-1,2-dihydro-1-(2-methoxybenzyl)-2-oxo-benzofuro(3,2-b)pyridin-3-kyseliny karboxylová a 6 ml 5N KOK v 10 ml methanolu se vaří za refluxu po dobu dvou hodin. Postupujeme jako obvykle a obdržíme 4-(1,4benzodicxan-6-yl)-1,2-dihydro-l-(2-methoxybenzyl)-2-oxo-benzofuro( 3,2-b)pyridin-3-kyseiinu karboxylovou, F.225c.
Analogicky obdržíme z ethylesteru 4-l(l,4-benzodioxan-6-yl)-2-(2-methoxybenzyloxy)-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylová 0-produkt alkylace 4-(1,4-benzodioxan-6-yl)-2-(2-methoxybenzyloxy)-benzofuro(3,2-b)-pyridin-3-kyselinu karboxylovou, F. 1790.
Analogicky dostanene z následujících ethylesterů 4-T-l,2-dihydro-l-(2-methoxybenzyl)-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylová, ethylesterů 4-T-2-(2-methoxybenzyloxy)-benzofuro(3,2-b)-pyridin3-kyseliny karboxylová, ethylesterů 4-T-l,2-dihydro-l-(3-methoxybenzyl)-2-oxo-benzofuro (3,2-b)-pyridin3-kyseliny karboxylová, ethylesterů 4-T-2-(3-methoxybenzyloxy)-benzofuro(3,2-b)pyridin3-kyseliny karboxylová, ethylesterů 4-T-l,2-dihydro-l-(4-methoxybenzyl)-2-oxo-benzofuro (3,2-b)-pyridin-3-kyseliny karboxylová, ethylesterů 4-T-2-(4-methoxybenzyloxy)-benzofuro(3,2-b)-pyridin3-kyseliny karboxylové, esthylesterů 4-T-l,2-dihydro-l-(3,4-methylendioxybenzyl)-2-oxobenzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-T-2(3,4-methyendioxybenzyloxy)-benzofuro(3,2-b)pyridin-3-kyseliny karboxylové, ethylesterů. 4-T-l,2-dihydro-l-(2-karboxymethyloxy-4-methoxybenzyl)-2-oxobenzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-T-2-(2-karboxymethyloxy-4-methoxybenzyloxy)-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-T-l,2-dihydro-l-(2,3-methylendioxybenzyl)-2-oxobenzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-T-2-(2,3-methylendioxybenzyloxy)-benzofuro(3,2-b)pyridin-3-kyseliny karboxylové, ethylesterů 4-T-l,2-dihydro-l-(2-methylthiobenzyl)-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-T-2-(2-methylthibenzyloxy)-benzofuro(3,2-b)pyridin -3-kyseliny karboxylové, ethylesterů 4-T-l,2-dihydro-l-(2,3-dimethoxybenzyl)-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesaerů 4-T-2-(2,3-dimethoxybenzyloxy)-benzofuro(3,2-b)-py— ridin-3-kyseliny karboxylové, ethylesterů 4-T-l,2-dihydro-l-(2,5-dimethoxybenzyl-2-oxo-benzofuro-(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-T-2-(2,5-dimethoxybenzyloxy)-benzofuro(3,2-b)-pyri din-3-kyseliny karboxylové , ethylesterů 4-T-l,2-dihydro-l-(2,1,3-benzothiazol-5-methyl)-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-T-2-(2,1,3-benzothiadiazol-5-methyloxy)-benzofuro (3,2-b)pyridin-3-kyseliny karboxylové, ethylesterů 4-T-l,2-dihydro-l-(3,4-methylendioxy-6-chlor-benzyl) -2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-T-2-(3,4-methylendioxy-6-chlor-benzyloxy)-benzofuro-(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-T-l,2-dihydro-l-(2-methoxybenzyl)-2-oxo-7-methylbenzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, ethylesterů 4-TR-2-(2-methoxybenzyloxy)-7-methyl-benzofuro(3,2-b) -pyridin-3-kyseliny karboxylové, ethylesterů 4-T-l,2-dihydro-l-(2-methoxybenzyl)-2-oxo-benzothieno (3,2-b)-pyridin-3-kyseliny karboxylové a ethylesterů 4-T-2-(2-methoxybenzyloxv)-benzothieno(3,2-b)-pyridin
3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl
2.3- dimerhoxyíenyl
2.4- dimerhoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxyme thy1oxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl tyto 4-T-l, 2-dihydro-l-( 2-methoxybenzyl)-2-oxo-benzofuro(J3,2-bJ) -pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzcdioxol-5-yl, F.230’
2- methoxyfenyl, F.223b
3- methoxyfenyl, draselná sůl, F.> 300ť
4- methoxyfenyl, draselná sůl, F. 258^
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl, F.2660
2.5- dimethoxyf enyl, F.2O10
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl , F.214°
2-methoxy-3-karboxymethyloxy-fenyl
2-nethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl, F.1930
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl, Γ.ΐθδ0
4-methylthiofenyl, F.2400
3- fluor-4-methoxyfenyl, F.2540
2.3- dihydro-5-benzofuryl , F.2675
4- methylfenyl , F.243<?
2- ethoxy-5-methoxyfenyl, F. 245ú
2.1.3- bem.zothiadiazol-5-yl
2.4.5- trinethcxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl dále 4-1-2- ( 2-methoxybenzyloxy) -benzofuro C’3,2-bJ -pyridin-3 kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzcdioxan-5-yl
1.3- benzcdioxol-4-yl
1.3- benzcdioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyf enyl, F. 105°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4.diethylamincfenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethcpxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-r-l,2-dihydro-l-(2-methcxybenzyl)-2-oxo-benzofuro C3,2-bJ pyridin 3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzcdioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxvfenyl,F. 22 3
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2,5-dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfeny1
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethvloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormerhoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- bsnzothiadiazol-5-yl
2.4.5- trimethcxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-2-Í3-methoxybenzyloxy)-benzofuro C3,2-bJ-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl 2-methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,F.174’
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-f enyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethvloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-meohoxyfenyl
2,2-dihydro-:-benzcfuryl
4- methy1f eny1
2- ethoxy-5-methoxyfenyl
2,1,3-benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-l,2-dihydro-l-(4-methoxybenzyl)-2-oxo-benzofuroC3,2-bDpyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,F. 2449
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluo ΣΊΓιθ thoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-feny1
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymetnyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-erhoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-2- ( 4-methoxybenzyloxy)-benzofuro(3,2-bj -pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F . 23 23
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormeohoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylamincfenyl
4-methylthiofenyl
3- fluor-4-methoxyf enyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-l,2-dihydro-l-(3,4-methylendioxybenzyl)-2-oxo-benzofuro (3,2-b}-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,draselná sůl, FX3OO“7
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimemhoxyfenyl
3.4- dimeohoxyfenyl
3.5- dimemhoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- aifluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2,3-dihydro-5-benzofuryl
4- methylfenyl
2-ethoxy-5-methoxyfenyl
2,1,3-benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3-chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl,
4-T-2-(3,4-methylendioxybenzyloxy)-benzofuroC3,2-bJ-pyridin-3kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfsny1
3- methoxyfenyl
4- methoxyf enyl, F. 85°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-l,2-dihydro-l-(2-karboxymethyloxy-4-methoxybenzyl)-2-oxoben zenfuro ,2-bQ-pyridin-3-kyseliny karboxylová, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzcdioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxy fenyl.
2.3- dimemhoxyfenyl
2.4- dimemhoxyfenyl
2.5- dimemhoxyfenyl
3.4- dimethoxyfenyl
3.5- dimemhoxyfenyl
2- ka rbc xymethy1oxy f eny1
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karbcxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4- T-2-(2-karbcxymethyloxy-4-methoxybenzyloxy)-benzofuro C3,2-bj-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxoI-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F . 217°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethopxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-.-1,2-dihydro-l-(2,3-methylendioxybenzyl)-2-oxo-benzofuro (3,2-bJ-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzcdioxol-5-yi
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F . 214°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2, Ξ-dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl
- 73 2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-ka rboxymethyloxy-feny1
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4- T-2-(2,3-methylendioxybenzyloxy)-benzo fůro C3,2-bJ-pyridin-3 kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzcdioxan-5-yl
1.3- benzcdioxol-4-yl
1.3- benzcdioxol-5-yi
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylrhiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzoíuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-l,2-dihydro-l-(2-methylthiobenzyl)-2-oxo-benzofuro£3,2-bD pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzcdioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl,F >3 00
2.3- dimerhoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4-karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karbcxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylohiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyf enyl
2-fluor-4-methoxyfenyl
4-T-2-(2-nethylthiobenzylcxy)-benzofuro C3,2-b)-pyridin-3-kyseliny karboxylová, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyf enyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfeny1
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormerhoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethcxyfenyl
4-ethoxyfenyl
4-diethylamir.of enyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-meuhoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethcoxyfenyl
3- chlor-4-meuhoxyfenyl
2-fluor-4-methoxyfenyl
4-T-l,2-dihydro-l-(2,3-dimethoxybenzyl)-2-oxo-benzofuro (3,2-b^-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl 2-methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F. 251°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyf enyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl
2-diflucrmethoxy-3-karboxymethyloxy-fenyl 2-diflucrmethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methcxyf emy1
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-2- ( 2,3-dimethoxybenzyloxy)-benzofuroQ3,2-i5-pyridin-3 kyseliny kareboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyf enyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
4-T-l, 2-dihydro-l- ( 2,5-dimethoxybenzyl-2-oxo-benzofurof3,2-la) pyridin-3-kys=iiny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl, F.253®
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F. 297^
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2,5-dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-2-difluormethoxy-fenyl 2-karboxymethyloxy-i-difluormethoxy-fenyl
2- trifluormemhoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl, F.197
4.diethylaminofenyl
4-methylthiofenyl·
3- fluor-4-methoxyfenyl, draselná sůl, F. 283^
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-menhoxyfenyl
2.1.3- benzomhiadiazel-5-yl
2.4.5- trimethcpxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-2-(2,5-dimethoxybenzyloxy)-benzofuro(3,2-bJ-pyridin-3 kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-ka rboxymethyioxy-4-me thoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl
2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-e thoxy fenyl
4-diethylaminofenyl
4—methvlmhiofenvl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-l,2-dihydro-l-(2,1,3-benzothiazol-5-methyl)-2-oxo-benzofuro (3,2-bOpyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, F. 114^
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-feny1 2-d i f1uc rmethoxy-4-ka rboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- urifluormethoxyfenyl
3- trifluormethoxyfenyl
4- urifluormethoxyfenyl
4-trifluormeuhoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-2-(2,1,3-benzothiadiazol-5-methyloxy)-benzofurof3,2-b}-pyri din-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimeohoxyfenyl
2.5- dimethoxyfenyl
3.4- dimeohoxyfenyl
3.5- dimethoxyfenyl
2-karboxymethyloxyfenyl
- k a r b o x y m e t h y 1 o x y f e n y 1
4-karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- d i fluc rmethoxyf eny1
4- di fluc rmethoxyf eny1
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-diflucrmethoxy-3-karboxymethyloxy-fenyl 2-diflucrmethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- orifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethcxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2-ethoxy-5-metnoxyfenyl
2.1.3- benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3-chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-l,2-dihydro-l-(3,4-methylendioxy-6-chlor-benzyl)-2-oxobenzofuro C3,2-b}-pyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- nethoxyfenyl
3- methoxyfenyl
4- methoxyfenyl, draselná sůl, F.Z300
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3,4-dimethoxyfenyl , 5-dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
- k a r b o x y m e t h y 1 o x y f e n y 1
2- difluormethoxyfenyl
3- i1fluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethcxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2,4,5-trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-7-2-( 3,4-methylendioxy-6-chlor-benzyloxy )-benzofuro()3,2-b)) pyridin-3-kyseliny karboxylová, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxcl-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyf enyl, F. 192°
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3,4-dimethoxyfenyl , 5-dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4-trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylamincfenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2, 3-dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2,1,3-benzothiadiazol-5-yl
2.4.5- trimethcpxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-l,2-dihydro-l-(2-methoxybenzyl)-2-oxo-7-methyl-benzofuro (3,2-bj-pyridín-3-kyseliny karboxylové, kde T fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxcl-4-yl
1.3- benzodioxo1-5-yl
2- methoxyf eny1
3- methoxyf eny1
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl
2-methoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-methoxy-fenyl
2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl
2-difluormethoxy-4-karboxymethyloxy-fenyl
2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylamir.cf enyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethzxyfenyl
3- chlor-4-memhoxyfenyl
2-fluor-4-methoxyfenyl
4-T-2-(2-methoxybenzyloxy)-7-methyl-benzofuro(3,2-b)-pyridin kyseliny karhcxylové, kde T znamená fenyl naftyl
1,4-benzcdicxan-5-yl
1.3- benzodioxci-4-yl
1.3- benzcdioxol-5-yl
2- methoxyfenyl
3- methoxyf eny1
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyioxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl 2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methyirhiofenyl
3- fluor-i-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-merhoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl
4-T-l,2-dihydro-l-(2-methoxybenzyl)-2-oxo-benzothieno£3,2-bJpyridin-3-kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzodioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzodioxol-5-yl
2- methoxyfenyl
3- methoxyfenyl
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3.4- dimethoxyfenyl
3.5- dimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfenyl
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl
2- trifluormethoxyfenyl
4-trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylaminofenyl
4-methylthiofenyl
3- fluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl
2- ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3- chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl a
4-T-2-(2-methcxybenzyloxy)-benzothienoC3,2-bJ -pyridin-3 kyseliny karboxylové, kde T znamená fenyl naftyl
1,4-benzcdioxan-5-yl
1.3- benzodioxol-4-yl
1.3- benzcdioxol-5-yl
2- methoxyfenyl
3- methoxyfeny1
4- methoxyfenyl
2.3- dimethoxyfenyl
2.4- dimethoxyfenyl
2.5- dimethoxyfenyl
3,4-dimethoxyfenyl 3,ódimethoxyfenyl
2- karboxymethyloxyfenyl
3- karboxymethyloxyfeny1
4- karboxymethyloxyfenyl
2- difluormethoxyfenyl
3- difluormethoxyfenyl
4- difluormethoxyfenyl
2-methoxy-3-karboxymethyloxy-fenyl 2-methoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-methoxy-fenyl 2-karboxymethyloxy-4-methoxy-fenyl
2-difluormethoxy-3-karboxymethyloxy-fenyl 2-difluormethoxy-4-karboxymethyloxy-fenyl 2-karboxymethyloxy-3-difluormethoxy-fenyl 2-karboxymethyloxy-4-difluormethoxy-fenyl
2- trifluormethoxyfenyl
3- trifluormethoxyfenyl
4- trifluormethoxyfenyl
4-trifluormethoxy-2-karboxymethyloxy-fenyl
3.4.5- trimethoxyfenyl
4-ethoxyfenyl
4-diethylamincfenyl
4-methylthiofenyl
3- íluor-4-methoxyfenyl
2.3- dihydro-5-benzofuryl
4- methylfenyl2-ethoxy-5-methoxyfenyl
2.1.3- benzothiadiazol-5-yl
2.4.5- trimethoxyfenyl
3-chlor-4-methoxyfenyl
2-fluor-4-methoxyfenyl .
Přiklad 3
Roztok 4,1 g ethylesterů 4-(1,4-benzodioxan-6-yl)-chlor -benzo-furo(3,2-b)pyridin-3-kyseliny karboxylové a 0,25 g tetrakis(trifenylfosfin)-palladium-(0) v 50 ml toluolu se smíchá s 10 ml vodného roztoku 2M uhličitanu sodného a 1,52 g
4-methoxyfenylborité kyseliny v 25 ml methanolu a 1 hodinu se v inertní atmosféře za refluxu vaří.
Pracujeme jako obvykle a obdržíme ethylester 4-(1,4-benzodioxan-6-yl)-2-(4-methoxyfenyl)-benzofuro(3,2-b)-pyridin -3 kyseliny karboxylové.
Přiklad 4
Roztok 3,8g ethylesterú 4-(l,4-benzodioxan-6-yl)-2-chlorbenzofuro(3,2-b)pyridin-3-kyseliny karboxylové a 3,1 g uhličitanu česného v 40 ml DMF se smíchá s roztokem 1,7 g
3,4-methylendioxyfenolu v 20 ml dichlormethanu a přes noc se míchá. Pracujeme jako obvykle a dostaneme ethylester 4-(1,4-benzodioxan-6-yl)-2-(3,4-methylendioxy-fenoxy)benzofuro (3,2-b)-pyridin-3-kyseliny karboxylové.
Příklad 5
Roztok ig 1,2-dihydro-l,2(methoxybenzyl)-4-(4-methoxyfenyl) -2-oxo-7-nitrc-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, F.245, , připravené podle příkladu 1 a 2 v 25 ml methanolu se za normálního tlaku a při teplotě 20 C hydrogenuje na 1 g Raney-niklu až do klidu . Po filtraci se odstraní rozpouštědlo a dostaneme 7-amino-l,2-dihydro-l-(2-methoxybezylu)-4-(4-methoxyfenyl)-2-oxc-oenzofuro(3,2-b)-pyridin-3-kyselinu karboxylovou, F.268 .
Příklad 6
Roztek 6 g 7-amino-l,2-dihydro-l-(2-methoxybenzyl)-4-(4-methexyfenyl)-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové a 0,5 g titartetrachloridu v 100 ml methanolu se smíchá s 1 ml čerstvě destilovaného acetaldehydu. Poté se přidá 4 g narriumkyanberhydridu a míchá se 30 hodin. Přidá se polokoncentrovaná kyselina solná a postupuje se jako obvykle. Dostaneme
7-ethylamino-i,2-dihydro-l-(2-methoxybenzyl)-4-(4-methoxyfenyl)2-oxo-benzofuro(3,2-b)-pyridin-3-kyselinu karboxylovou.
Příklad 7
Roztok 4,85 g 4-(1,4-benzodioxan-6-yl-l,2-dihydro—l-(3,4-methylendioxy-benzyl)-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové a 0,2 g dimethylaminopyridinu v 50 ml pyridinu se smíchá s 5 ml thionylchloridu a 1,57 g fenylsulfonamidu. Míchá se hodin a poté se postupuje jako obvykle. Obdržíme 4-(l,4-benzodioxan-6-yl)-1,2-dihydro-l-(3,4-methylendioxy-benzyl)-2-oxo-3(fenyl-sulfonamidokarbonyl)-benzofuro(3,2-b)-pyridin.
Příklad 3
Analogicky k příkladu 1 dostaneme reakcí ethylesteru
4- (4-methoxyfenyl)-1,2-dihydro-2-oxo-benzofuro(3,2-b)-pyridin-3kyseliny karboxylové s následujícími T-chloridy, kde T benzyl
2- trifluormethylbenzyl
3- fenoxybenzyl
2-fluorbenzyl
2-methylbenzyl
2-kyanbenzyl naftylmemhyl
2- trifluormethoxybenzyl
3- trifluormethoxybenzyl
2-methoxy-5-acetobenzyl
2-chlorbenzyl
6-fluor-1,3-benzodioxan-8-ylmethyl
2-ethoxybenzyI
5- brom-2-methoxybenzyl
3.4.5- trimethoxybenzyl
2.4.5- trimethcxybenzyl
2-isoprcpylbenzyl
3.5- dimethoxybenzyl
2.6- dimemhoxybenzyl
1, i-benzcdioxan-6-ylmethyl
2,1,3-benzothiadiazol-4-ylmethyl
2,4-dimethoxybenzylů
6- methoxy-l,2-benzodioxol-5-ylmethyl
6-chlor-2,1,3-benzothiadiazol-5-ylmethyl znamená následující ethylestery 4-(4-methoxyfenyl)-1,2-dihydro-l-T-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, kde T znamená benzyl, F.183*
2- mrifluormethylbenzyl, F.-226
3- f enoxybenzyl, Rfc0,39
2-fluorbenzyl, Rft0,19
2-methylbenzyl, F 200’
2-kyanbenzyl naftylmethyl, F.2735
2- trifluromethoxybenzyl, R%0/4
3- trifluormethoxybenzyl, F 159e
2-methoxy-5-acetobenzyl, Rfc0,3
2-chlorbenzyl, Rfc0,36
6-fluor-1,3-benzodioxan-8-ylmetzhyl, Rfa0,5 2-ethoxybenzyl, Rfc 0,3
5- brom-2-methoxybenzyl, Ffc0,34
3.4.5- trimethcxybenzyl, Ηίς0,37
2.4.5- trimethoxybenzyl, Rfc0,4 2
2-isopropylbenzyl, R^0,38
3.5- dimethoxybenzyl, R^0,36
2,ó-dimethoxybenzyl, R^_0,3 8
1,4benzodioxan-6-ylmethyl, Rť^, 0,51
2,1,3-benzothiadiazo1-4-ylmethyl, Rfg0,36
2,4-dimethoxybenzyl
6- methoxy-l,3-benzodioxol-5-ylmethyl
6-chlor-2,1,3-benzothiadiazol-5-ylmethyl jakož i následující ethylestery 4-(4-methoxyfenyl)-2-(T-oxy) -benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové, kde T znamená benzyl, F.113P
2- mrifluormethylbenzyl, F.10lí’
3- f enoxybenzyl, Rf^0,71
2-fluorbenzyl, Rfc0,63
2-r.ethyibenzyl, F 113”
2-kyanbenzyl naftylmethyl, F 140°
2- trifluormethoxybenzyl, F.1130
3- trifluormethoxybenzyl, Rfc0,71
2-methoxy-5-acxetobenzyl, F.149*
2-chlorbenzyl, F.115p
6-f luor-1,3-benzodioxan-8-ylmethyl, F, -154’ 2-ethoxybenzyl, F.Só^
5-brom,-2-methoxybenzyl, F.147^
3.4.5- trimethoxybenzyl, F.142°
2.4.5- trimethoxybenzyl, F.115p
2-isopropylbenzyl, F.84^
3.5- dimethoxybenzyl, F.IOS^
2.6- dimethoxybenzyl, F.141*7
1.4- benzodioxan-6-ylmethyl, F.146*
2,1,3-benzothiadiazol-4-ylmethyl, F.1729
2.4- dimethoxybenzyl
6-methoxy-l,3-benzodioxol-5-ylmethyl
6-chlor-2,1,3-benzothiadiazol-5-ylmethyl.
Analogicky k příkladu 2 dostaneme hydrolýzou esterů z uve děných 4 - (4-methoxyfenyl)-1, 2-dihydro-l-T-2-oxo-benzofuro(3,2-b) pyridin-3-kyseliny karboxylové následující 4-(4-methoxyfenyl)
-1,2-dihydro-i-T-2-oxo-benzopfuro(3,2-b)-pyridin-3-kyseliny karboxylové , kde T znamená benzyl, F.25 29
2- rrifluormethylbenzyl, F.2949
3- f enoxyoenzyl, F..183ť’
2-fluorbenzyl, Ε.253ΰ
2-methylbenzyl, F.24 5*
2-kyanberzyl naftylmethyl, F.>300e
2- rrifluormethoxybenzyl, F.218^
3- nrifluormethoxybenzyl, F.2459
2-methoxy-5-acetobenzyl, F.249c?
2-ohlorbenzyl, F.102'“1
6-fluor-1,3-benzodioxan-8-ylmethyl, F, >300” 2-ethoxybenzyl, F 239^
5- brom-2-methoxybenzyl, F. 260^
3.4.5- trimethoxybenzyl, F.2430
2.4.5- trimethcxybenzyl, F.2320
2-isopropylbenzyl, 7.220^
3.5- dimethoxybenzyl, F.2150
2.6- dimethoxybenzyl, F.2329
1.4- benzodioxan-6-ylmethyl, F-2399
2,1,3-benzothiadiazol-4-ylmethyl, F.192°
2.4- dimethoxybenzyl
6- methoxy-l,3-benzodioxol-5-ylmethyl
6-chlor-2,1,3-benzothiadiazol-5-ylmethyl.
Příklad 9
Ethylester 8-brom-l-(2,5-dimethoxybenzyl)-4-(4-methoxyfenyl) -1,2-dihydro-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxyse analogicky k příkladu 33 uvede do reakce a kyselinou fenvlboritou a vznikne ethylester 8-fenyl-l-(2,5-dimethoxybenzyl) -4-14-methoxyfenyl) -1,2-dihydro-2-oxo-benzofuro(3,2-b)-pyridin-3 kyseliny karboxylové, F.216. Hydrolýzou esterů pak dostaneme
8-fenyl-l-(2,5-dimethoxybenzyl)-4-(4-methoxyfenyl)-l,2-dihydro-2oxobenzofuro(3,2-b)-pyridin-3-kyselinu karboxylovou, F. 270.^
Příklad 10
Roztok ethylesteru 7-amino-l,2-dihydro-l-(2-methoxybenzyl)
-4-'4-methoxyfenyl)-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové v DMF se smíchá s ekvimolárním množstvím mesylchloridu a uhličitanu česného a míchá se jednu hodinu. Po obvyklém zpracování dostaneme ethylester 7-methylsuldonylamino-l,2-dihydro —1- (2-methoxybenzyl)-4-(4-methoxyfenyl)-2-oxo-benzofuro(3,2-b) pyridin-3-kyseliny karboxylové.
Analogicky obdržíme sloučeniny ethylester 7-fenylsulfionylamino-1,2-dihydro-l-(2-methoxybenzyl)
-4-(4-methoxyfenyl)-2-oxo-benzofuro(3,2-b)-pyridin-3-kyseliny karboxylové a ethylester 7-tenzylsulfonylamino-l,2-dihydrro-l-(2-methoxybenzyl -4-(4-methoxyfenyl)-2-oxo-benzofuro(3,2-b)pyridin-3-kyseliny karboxy love.
Hydrolýzou esterů dostaneme volné karboxylové kyseliny > 7-methylsulfonylamino-l,2-dihydro-l-(2-methoxybenzyl)-4-(4-metho xyfenyl)-2-oxc-benzofuro(3,2-b)-pyridin-3-kyselinu karboxylovou, * 7-fenylsulfonylamino-1,2-dihydro-l-(2-methoxybenzyl)-4-(4-mwthoxyfenyl)-2-oxo-benzofuro(3,2-b)-pyridin-3-kyselinu karboxylovou,
7-benzylsulfonylamino-1,2-dihydro-l-(2-methoxybenzyl)-4-(4-methoxyfenyl )-2-oxo-benzofuro(3,2-b)-pyridin-3-kyselinu karboxylovou.
Příklad A - injekce
Roztok 100 účinné látky podle vzorce I a 5 g dinatriumhydrogenfosfátu se v 3 1 dvakrát destilované vody upraví 2 n kyselinou solnou na pH 6,5, sterilně se zfiltruje a naplní do injekcí, za sterilních podmínek se lyofilizuje a sterilně se uzavře. Každá injekce obsahuje 5 mg účinné látky.
Příklad B - čípky
Směs 20 g účinné látky podle vzorce I se roztaví s 100 g sojového lecithinu a 1400 g kakaového másla, odleje se do forem a nechá se ochladit. Každý čípek obsahuje 20 mg účinné látky.
Příklad C - roztok
Přpraví se roztok z 1 g účinné látky podle vzorce I, 9,38 g NaH PO í 2 H 0, 28,43 g Na HPO .12 H 0 a O,L benzalkoniumchloridu v 540 ml dvakrát destilované vody. Upraví se na pH 6,8, doplní na 1 litr a sterilizuje ozářením. Tento roztok lze užívat ve formě očních kapek .
Příklad D - mast
Smíchá se 500 mg účinné látky podle vzorce I s 99,5 g vazelíny za aseptických podmínek.
Příklad Ξ - tablety
Směs lg účinné látky podle vzorce I, 4 kg laktosy, 1,2 kg bramborového škrobu, 0,2 kg talku a 0,1 kg magnesiumstearátu se obvyklým způsobem zpracuje na tablety tak, že každá tableta obsahuje 10 mg účinné látky.
Příklad F - dražé
Analogicky k příkladu E se zhotoví tablety, které se pak obvyklým způsobem povlečou sacharosou, bramborovým škrobem, talkem,tragantem a barvivém.
Přiklad G - kapsle kg účinné látky podle vzorce I se obvyklým způsobem zpracuje a naplní do kapslí z tvrdé želatiny , takže každá kapsle obsahuje 20 mg účinné látky.
Přiklad H - ampule
Roztok 1 kg účinné látky podle vzorce Iv 60 1 dvakrát destilované vody se sterilně zfiltruje, naplní do . ampulí, za sterilních podmínek se lyofilizuje a sterilně se uzavře. Každá ampule obsahuje 10 mg účinné látky.
Claims (5)
- Patentové nároky S1. Sloučeniny podle vzorce I (JíCO' σιCc oczx cni.íc r<ΓΚRz kde níže uvedená označení mají příslušný význam-Y-Z- -Nřť-CO- , -N=C(OR7 ) -nebo -N=CR3-zR1 Ar,R2 COOR6, CN, lH-tetrazol-5-yl nebo CONHSO2Ar,R3, R4, R5 vždy nezávisle na sobě R6, CR6, S(O)mR6, HalNC2 , NR6R°, NHCOR6, NHSC^R6, OCOR6, COOR6 nebo CN,R6 , R6R'R8Ar vždy nezávisle na sobě H, Alkyl s 1 až 6 C-atomy, benzyl nebo fenyl (CH2 )nAr,Ar nebo OAr nesubstituovaný nebo jednou, dvakrát nebo třikrát R? , RlOnebo Rllsubstituovaný fenyl nebo nesubstituovaný naftyl nebo jedna nesubstituovaná nebo ve fenylová části jednou nebo dvakrát R^ nebo R^-®substituovanáD skupina nebo nesubstituovaná nebo jednou nebo dvakrát R^ v cyklohexadienylovém nebo R10substituovaná dílu r9zr10, r11 vždy nezávisle na sobě R^, OR^, Hal, CF3, OCF3 ,OCHF2, OCH2F, N02, NR6R6' NHCOR6, CN, NHSO2R6, COOR6, CORS, CONHSO2Ar, O(CH2)nR2, O(CH2)nOR6nebo S(O)mR6,E CH2, S nebo O,D karbony 1 nebo £C(R6R6jjn ,Hal F, Cl, Br nebo I,X O nebo S, m 0,1 nebo 21 nebo 2, jakož i jejich solí.
- 2. a) l,2-dihydro-l-(2-methoxybenzyl)-4-(4-methoxyfenyl)-2oxobenzofuro(3,2-b)pyridin-3-kayselina karboxylová ,b) 2-(2-methoxybenzyloxy)-4-(4-methoxyfenyl)-benzofuro (3,2-b)-pyridin-3-kyselina karboxylová,c) 4-(1,4-benzodioxan-6-yl)-1,2-dihydro-l-(2-methoxybenzyl) 2-oxo-benzofuro(3,2-b)pyridin-3-kyselina karboxylová,d) 2-(2-methoxy-fenoxy)-4-(4-methoxyfenyl)-benzofuro(3,2-b) -pyridin-3-kyselina karboxylová ,e) 4-(1,4-benzodioxan-6-yl)—1,2-dihydro-l-(2-methoxybenzyl )-2-oxo-3-(lH-tetrazol-5-yl)-benzofuro(3,2-b)pyridin,f) 1,2-dihydro-l-(2,3-methylendioxybenzyl)-4-(4-methoxyfenyl) 2-oxo-benzofuro(3,2-b)pyridin-3-kyselina karboxylová,g) 1,2-dihydro-l-(2,3-methylendioxybenzyl)-7-methyl-4-(4trifluormethoxyfenyl)-2-oxo-benzofuro(3,2-b)pyridinkyselina karboxylová,h) 1,2-dihydro-l-(2,3-methylendioxybenzyl)-7-methyl-4-(4methoxyfenyl)-2-oxo-benzothieno(3,2-b)pyridin-3-kyselina karboxylová,i) 1,2-dihydro-l-(1,1,3-benzothiadiazol-5-methyl)-4-(4-methoxyfenyl ) -2-oxo-benzof uro ( 3 ,2-b)pyridin-3-kyselina karboxylová.
- 3. Způsob přípravy sloučenin o vzorci I podle nároku 1, jakož i jejích solí, vyznačený tím, že (a) se k přípravě sloučeniny o vzorci I kde100-Y-Z znamená NR7-CO- nebo -N=C(OR^)ř se uvede do reakce sloučenina o vzorci IIR1, R2, R2 , R^, R2 a X mají významy uvedené v nároku 1 se sloučeninou o vzorci III r7-q iii kdeQ znamená Cl,Br,I nebo volnou nebo reakce schopnou funkční odloučenou OH-skupinu a 7 ,R ma význam udaný v nároku 1, mebo že seb) pro přípravu sloučeniny o vzorci I, kde-Y-Z- znamená N=C(Ar)sloučenina o vzorci IV101JV <Q znamená Cl,Br nebo I aR1 ,r3 ,Ι?4 ,Ι?5 a X mají význam udaný v nároku 1 uvede do reakce se sloučeninou boru o vzorci VAr-BLL' V kdeL,L' znamená vždy nezávisle na sobě OH, OCH3 , OC2H5nebo OC β H-j aAr má význam udaný v nároku 1 nebo že sec) pro přípravu sloučeniny o vzorci I, kde-Y-Z- znamená -N=C(OAr)sloučenina o vzorci IV, kdeQ znamená Cl,Br.neba I,102 uvede do reakce se sloučeninou o vzorci VIAr-OH VI, a/nebo že se ve sloučenině o vzorci I jeden nebo několik zbytků R 1 , R 2, R 3, R 4 , a/nebo R 5 přemění na jeden nebo několik zbytků r\ R2, R3 , R4, a/nebo R2 když se např.i) nitroskupina redukuje na aminoskupinu, ii) ester skupina se hydrolyžuje na karboxy skupinu, iii) aminoskupina se redukční aminací přemění na alkylovaný amin, iv) karboxy skupina se přemění na sulfonamidokarbonyl skupinu a/nebo báze nebo kyselina o vzorci I na jednu z jejich solí.
- 4. Způsob přípravy farmaceutických přípravků, vyznačený tím, že se sloučenina o vzorci I podle nároku 1 a/nebo jedna z jejich fyziologicky nezávadných solí upraví spolu s alespoň jednou pevnou, tekutou nebo polotekutou nosnou nebo pomocnou látkou do vhodné dávkovači formy.Farmaceutický přípravek, vyznačený sloučeniny o vzorci I podle nároku 1 fyziologicky nezávadných solí.obsahem alespoň jedné a/nebo jednou z jejich6.Sloučeniny o vzorci I podle nároku 1 a jejich fyziologicky nezávadné soli za účelem potírání nemocí.
- 7. Léčiva o vzorci L podle nároku 1 a jejich fyziologicky nezávadné soli jako antagonisty endothelin-receptoru.- 103 8. Použití sloučenin o vzorci I podle nároku 1 a/nebo jejich fyziologicky nezávadných solí pro přípravu léčiv.
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| DE19527568A DE19527568A1 (de) | 1995-07-28 | 1995-07-28 | Endothelin-Rezeptor-Antagonisten |
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| US6291442B1 (en) | 1998-02-03 | 2001-09-18 | The General Hospital Corporation | Pharmacological modulators of voltage-gated potassium ion channels |
| IL125659A (en) † | 1998-08-05 | 2002-09-12 | Cadent Ltd | Method and device for three-dimensional simulation of a structure |
| US6638929B2 (en) | 1999-12-29 | 2003-10-28 | Wyeth | Tricyclic protein kinase inhibitors |
| DE10155076A1 (de) * | 2001-11-09 | 2003-05-22 | Merck Patent Gmbh | Verwendung von Endothelin-Rezeptor-Antagonisten zur Behandlung von Tumorerkrankungen |
| JP5082033B2 (ja) | 2001-12-21 | 2012-11-28 | エグゼリクシス パテント カンパニー エルエルシー | Ｌｘｒのモジュレーター |
| US7482366B2 (en) | 2001-12-21 | 2009-01-27 | X-Ceptor Therapeutics, Inc. | Modulators of LXR |
| HK1080467B (zh) * | 2002-02-22 | 2008-02-01 | Bayer Healthcare Llc | 用於治疗过度增生疾病的苯并呋喃和苯并噻吩衍生物 |
| KR101186386B1 (ko) * | 2003-08-29 | 2012-09-26 | 오노 야꾸힝 고교 가부시키가이샤 | Ｓ１ｐ 수용체 결합능을 갖는 화합물 및 그 의약 용도 |
| WO2015088564A1 (en) * | 2013-12-13 | 2015-06-18 | Sunovion Pharmaceuticals Inc. | P2x4 receptor modulating compounds |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0256485A (ja) * | 1988-04-27 | 1990-02-26 | Glaxo Group Ltd | ラクタム誘導体 |
| RU2086544C1 (ru) | 1991-06-13 | 1997-08-10 | Хоффманн-Ля Рош АГ | Бензолсульфонамидные производные пиримидина или их соли, фармацевтическая композиция для лечения заболеваний, связанных с активностью эндотелина |
| DE69232072T2 (de) | 1991-11-05 | 2002-06-20 | Smithkline Beecham Corp., Philadelphia | Endothelin-rezeptor-antagonisten |
| ZA939516B (en) | 1992-12-22 | 1994-06-06 | Smithkline Beecham Corp | Endothelin receptor antagonists |
| DK0617001T3 (da) | 1993-03-19 | 2000-04-17 | Merck & Co Inc | Phenoxyphenyleddikesyrederivater |
| US6075037A (en) * | 1994-06-09 | 2000-06-13 | Smithkline Beecham Corporation | Endothelin receptor antagonists |
-
1995
- 1995-07-28 DE DE19527568A patent/DE19527568A1/de not_active Withdrawn
-
1996
- 1996-07-12 TW TW085108491A patent/TW367328B/zh active
- 1996-07-16 SK SK924-96A patent/SK92496A3/sk unknown
- 1996-07-19 AU AU60607/96A patent/AU6060796A/en not_active Abandoned
- 1996-07-19 EP EP96111677A patent/EP0755934A1/en not_active Withdrawn
- 1996-07-25 CZ CZ962197A patent/CZ219796A3/cs unknown
- 1996-07-26 JP JP8214052A patent/JPH0940678A/ja active Pending
- 1996-07-26 BR BR9603164A patent/BR9603164A/pt not_active Application Discontinuation
- 1996-07-26 HU HU9602054A patent/HUP9602054A3/hu unknown
- 1996-07-26 US US08/687,922 patent/US5700807A/en not_active Expired - Fee Related
- 1996-07-26 ZA ZA9606399A patent/ZA966399B/xx unknown
- 1996-07-26 NO NO963131A patent/NO963131L/no unknown
- 1996-07-26 CA CA002182156A patent/CA2182156A1/en not_active Abandoned
- 1996-07-26 MX MX9603045A patent/MX9603045A/es unknown
- 1996-07-26 PL PL96315422A patent/PL315422A1/xx unknown
- 1996-07-26 KR KR1019960030674A patent/KR970006305A/ko not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| NO963131D0 (no) | 1996-07-26 |
| SK92496A3 (en) | 1997-07-09 |
| BR9603164A (pt) | 1998-05-05 |
| HU9602054D0 (en) | 1996-09-30 |
| MX9603045A (es) | 1997-01-31 |
| CA2182156A1 (en) | 1997-01-29 |
| HUP9602054A2 (en) | 1997-11-28 |
| ZA966399B (en) | 1997-02-19 |
| KR970006305A (ko) | 1997-02-19 |
| US5700807A (en) | 1997-12-23 |
| AU6060796A (en) | 1997-02-06 |
| EP0755934A1 (en) | 1997-01-29 |
| PL315422A1 (en) | 1997-02-03 |
| TW367328B (en) | 1999-08-21 |
| NO963131L (no) | 1997-01-29 |
| HUP9602054A3 (en) | 1998-07-28 |
| DE19527568A1 (de) | 1997-01-30 |
| JPH0940678A (ja) | 1997-02-10 |
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