IL108507A - Phenyl Sulfonamides are converted, their preparation and pharmaceutical preparations containing them - Google Patents
Phenyl Sulfonamides are converted, their preparation and pharmaceutical preparations containing themInfo
- Publication number
- IL108507A IL108507A IL10850794A IL10850794A IL108507A IL 108507 A IL108507 A IL 108507A IL 10850794 A IL10850794 A IL 10850794A IL 10850794 A IL10850794 A IL 10850794A IL 108507 A IL108507 A IL 108507A
- Authority
- IL
- Israel
- Prior art keywords
- phenyl
- amino
- hydroxy
- compound
- ethyl
- Prior art date
Links
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical class NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 174
- -1 substituted alkyl epoxide Chemical class 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 34
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 27
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 14
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
- 208000008589 Obesity Diseases 0.000 claims abstract description 8
- 235000020824 obesity Nutrition 0.000 claims abstract description 8
- 102000015779 HDL Lipoproteins Human genes 0.000 claims abstract description 6
- 108010010234 HDL Lipoproteins Proteins 0.000 claims abstract description 6
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 6
- 208000007920 Neurogenic Inflammation Diseases 0.000 claims abstract description 4
- 230000010243 gut motility Effects 0.000 claims abstract 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 39
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 229910052757 nitrogen Chemical group 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 239000011593 sulfur Chemical group 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 229940124530 sulfonamide Drugs 0.000 claims description 20
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 16
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 150000003456 sulfonamides Chemical class 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 101100134929 Gallus gallus COR9 gene Proteins 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- XKNAGLMNQADBQE-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=CC(OC=3C=CN=CC=3)=CC=2)=N1 XKNAGLMNQADBQE-UHFFFAOYSA-N 0.000 claims description 2
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- WYQUFJJNTIGKQS-UHFFFAOYSA-N n-[4-[2-[[2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethyl]phenyl]-2-phenylethanesulfonamide Chemical compound C=1C=C(O)C=CC=1OCC(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)CCC1=CC=CC=C1 WYQUFJJNTIGKQS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 230000003247 decreasing effect Effects 0.000 claims 2
- GSFUSGKNYXRUQM-UHFFFAOYSA-N 5-chloro-2-methoxy-n-(2-methylpropyl)benzamide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCC(C)C GSFUSGKNYXRUQM-UHFFFAOYSA-N 0.000 claims 1
- HOOJNACMGWJRMJ-UHFFFAOYSA-N n-[4-[2-[(2-hydroxy-3-pyridin-3-yloxypropyl)amino]ethyl]phenyl]quinoline-3-sulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C=C3C=CC=CC3=NC=2)C=CC=1CCNCC(O)COC1=CC=CN=C1 HOOJNACMGWJRMJ-UHFFFAOYSA-N 0.000 claims 1
- KOKQDIGRUUTJDV-UHFFFAOYSA-N n-[4-[2-[[2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=C(O)C=CC=1OCC(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C1=CC=CC=C1 KOKQDIGRUUTJDV-UHFFFAOYSA-N 0.000 claims 1
- NHRGQKNRPMOPPW-UHFFFAOYSA-N n-[4-[2-[[3-(4-amino-3-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]phenyl]quinoline-3-sulfonamide Chemical compound C1=C(C#N)C(N)=CC=C1OCC(O)CNCCC(C=C1)=CC=C1NS(=O)(=O)C1=CN=C(C=CC=C2)C2=C1 NHRGQKNRPMOPPW-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 17
- 238000005859 coupling reaction Methods 0.000 abstract description 5
- 230000004130 lipolysis Effects 0.000 abstract description 5
- 230000009467 reduction Effects 0.000 abstract description 5
- 230000008878 coupling Effects 0.000 abstract description 4
- 238000010168 coupling process Methods 0.000 abstract description 4
- 239000000935 antidepressant agent Substances 0.000 abstract description 2
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 abstract description 2
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 abstract description 2
- 102000016959 beta-3 Adrenergic Receptors Human genes 0.000 abstract description 2
- 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 abstract description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 2
- 239000000048 adrenergic agonist Substances 0.000 abstract 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 abstract 1
- 102000016967 beta-1 Adrenergic Receptors Human genes 0.000 abstract 1
- 108010014494 beta-1 Adrenergic Receptors Proteins 0.000 abstract 1
- 230000003389 potentiating effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 161
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 159
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 133
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 106
- 239000000243 solution Substances 0.000 description 90
- 238000005481 NMR spectroscopy Methods 0.000 description 85
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 61
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
- 235000019439 ethyl acetate Nutrition 0.000 description 46
- 150000001412 amines Chemical class 0.000 description 40
- 238000000746 purification Methods 0.000 description 39
- 238000003818 flash chromatography Methods 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 239000000741 silica gel Substances 0.000 description 31
- 229910002027 silica gel Inorganic materials 0.000 description 31
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 150000002118 epoxides Chemical class 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 238000003756 stirring Methods 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 17
- 235000011114 ammonium hydroxide Nutrition 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 239000000908 ammonium hydroxide Substances 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 10
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 10
- 239000012298 atmosphere Substances 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 9
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 9
- 150000004985 diamines Chemical class 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- LNPMZQXEPNWCMG-UHFFFAOYSA-N 4-(2-aminoethyl)aniline Chemical compound NCCC1=CC=C(N)C=C1 LNPMZQXEPNWCMG-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- 101150041968 CDC13 gene Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- AIHIHVZYAAMDPM-QMMMGPOBSA-N [(2s)-oxiran-2-yl]methyl 3-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)OC[C@H]2OC2)=C1 AIHIHVZYAAMDPM-QMMMGPOBSA-N 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 5
- 238000012746 preparative thin layer chromatography Methods 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 4
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 150000002828 nitro derivatives Chemical class 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- VSAXLHSQUHPTCS-UHFFFAOYSA-N quinoline-3-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CN=C21 VSAXLHSQUHPTCS-UHFFFAOYSA-N 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
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- KURDKBAAQRGXSB-UHFFFAOYSA-N tert-butyl n-(4-nitrophenyl)sulfonylcarbamate Chemical compound CC(C)(C)OC(=O)NS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 KURDKBAAQRGXSB-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
- C07C311/13—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/14—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
- C07C311/44—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
- C07C311/46—Y being a hydrogen or a carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
- C07C311/47—Y being a hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Child & Adolescent Psychology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
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|---|---|---|---|
| US1568993A | 1993-02-09 | 1993-02-09 | |
| US08/168,105 US5451677A (en) | 1993-02-09 | 1993-12-15 | Substituted phenyl sulfonamides as selective β 3 agonists for the treatment of diabetes and obesity |
Publications (2)
| Publication Number | Publication Date |
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| IL108507A0 IL108507A0 (en) | 1994-05-30 |
| IL108507A true IL108507A (en) | 1998-09-24 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| IL10850794A IL108507A (en) | 1993-02-09 | 1994-02-01 | Phenyl Sulfonamides are converted, their preparation and pharmaceutical preparations containing them |
Country Status (13)
| Country | Link |
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| US (1) | US5451677A (de) |
| EP (1) | EP0611003B1 (de) |
| JP (1) | JP2690006B2 (de) |
| AT (1) | ATE154594T1 (de) |
| AU (1) | AU670477B2 (de) |
| CA (1) | CA2114712A1 (de) |
| DE (1) | DE69403823T2 (de) |
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| ES (1) | ES2104259T3 (de) |
| GR (1) | GR3024672T3 (de) |
| IL (1) | IL108507A (de) |
| WO (1) | WO1994018161A1 (de) |
| ZA (1) | ZA94846B (de) |
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| US5705515A (en) * | 1994-04-26 | 1998-01-06 | Merck & Co., Inc. | Substituted sulfonamides as selective β-3 agonists for the treatment of diabetes and obesity |
| US5561142A (en) * | 1994-04-26 | 1996-10-01 | Merck & Co., Inc. | Substituted sulfonamides as selective β3 agonists for the treatment of diabetes and obesity |
| IL113410A (en) * | 1994-04-26 | 1999-11-30 | Merck & Co Inc | Substituted sulfonamides having an asymmetric center and pharmaceutical compositions containing them |
| US5627200A (en) * | 1994-09-26 | 1997-05-06 | Pfizer Inc | β3 -Adrenoceptor agonists and antagonists for the treatment of intestinal motility disorders, depression, prostate disease and dyslipidemia |
| AU5289496A (en) * | 1995-04-14 | 1996-10-30 | Tokyo Tanabe Company Limited | Novel aryloxypropanolamino(phenyl)propanol compounds |
| CA2220399A1 (en) * | 1995-05-10 | 1996-11-14 | Pfizer Inc. | .beta.-adrenergic agonists |
| US6075040A (en) | 1996-09-05 | 2000-06-13 | Eli Lilly And Company | Selective β3 adrenergic agonists |
| KR19990045727A (ko) * | 1995-09-21 | 1999-06-25 | 피터 지. 스트링거 | 선택적 β3 아드레날린 효능제 |
| ZA967892B (en) * | 1995-09-21 | 1998-03-18 | Lilly Co Eli | Selective β3 adrenergic agonists. |
| EP0858340A4 (de) * | 1995-11-01 | 1999-12-29 | Merck & Co Inc | Kombinationstherapie zur behandlung des diabetes und der obesität |
| US5847008A (en) * | 1996-02-02 | 1998-12-08 | Merck & Co., Inc. | Method of treating diabetes and related disease states |
| US6090836A (en) * | 1996-02-02 | 2000-07-18 | Merck & Co., Inc. | Benzisoxazole-derived antidiabetic compounds |
| US5859051A (en) * | 1996-02-02 | 1999-01-12 | Merck & Co., Inc. | Antidiabetic agents |
| DE69720429T9 (de) * | 1996-02-02 | 2004-09-23 | Merck & Co., Inc. | Heterocyclische verbindungen als antidiabetische mittel und für die behandlung von fettleibigkeit |
| US6020382A (en) * | 1996-02-02 | 2000-02-01 | Merck & Co., Inc. | Method of treating diabetes and related disease states |
| ATE245622T1 (de) * | 1996-02-02 | 2003-08-15 | Merck & Co Inc | Antidiabetische mittel |
| ATE203515T1 (de) * | 1996-03-29 | 2001-08-15 | Searle & Co | Meta-substituierte phenylsulphonamidderivate |
| EP0827746B1 (de) | 1996-09-05 | 2002-04-03 | Eli Lilly And Company | Carbazolanaloge als selektive beta3-adrenergische Agonisten |
| US5908830A (en) * | 1996-10-31 | 1999-06-01 | Merck & Co., Inc. | Combination therapy for the treatment of diabetes and obesity |
| US5994398A (en) * | 1996-12-11 | 1999-11-30 | Elan Pharmaceuticals, Inc. | Arylsulfonamides as phospholipase A2 inhibitors |
| US6160000A (en) * | 1996-12-23 | 2000-12-12 | Merck & Co., Inc. | Antidiabetic agents based on aryl and heteroarylacetic acids |
| US6090839A (en) * | 1996-12-23 | 2000-07-18 | Merck & Co., Inc. | Antidiabetic agents |
| CA2272285C (en) * | 1997-01-23 | 2006-11-21 | Yamanouchi Pharmaceutical Co., Ltd. | Amide derivatives and medicinal compositions thereof |
| JP2001509166A (ja) * | 1997-01-28 | 2001-07-10 | メルク エンド カンパニー インコーポレーテッド | 糖尿病および肥満の治療のためのβ▲下3▼作動薬としてのチアゾールベンゼンスルホンアミド |
| US6011048A (en) * | 1997-01-28 | 2000-01-04 | Merck & Co., Inc. | Thiazole benzenesulfonamides as β3 agonists for treatment of diabetes and obesity |
| ES2221204T3 (es) * | 1997-10-17 | 2004-12-16 | Yamanouchi Pharmaceutical Co. Ltd. | Derivados de amidas o sales de los indicados derivados. |
| AU1617499A (en) * | 1997-12-05 | 1999-06-28 | Eli Lilly And Company | Selective beta3 adrenergic agonists |
| CO5011072A1 (es) | 1997-12-05 | 2001-02-28 | Lilly Co Eli | Etanolaminas pirazinil substituidas como agfonistas de los receptores |
| UA62993C2 (en) * | 1997-12-19 | 2004-01-15 | Bayer Ag | CHROMAN DERIVATIVES SUBSTITUTED ON CARBOXYLIC GROUP USED AS AGONISTS OF b-3-ADRENORECEPTOR |
| US6051586A (en) * | 1997-12-19 | 2000-04-18 | Bayer Corporation | Sulfonamide substituted chroman derivatives useful as beta 3 adrenoreceptor agonists |
| US6469031B1 (en) | 1998-12-18 | 2002-10-22 | Bayer Corporation | Carboxyl substituted chroman derivatives useful as beta 3 adrenoreceptor agonists |
| WO1999032475A1 (en) * | 1997-12-19 | 1999-07-01 | Bayer Corporation | Novel sulfonamide substituted chroman derivatives useful as beta-3 adrenoreceptor agonists |
| US6043253A (en) * | 1998-03-03 | 2000-03-28 | Merck & Co., Inc. | Fused piperidine substituted arylsulfonamides as β3-agonists |
| WO1999051564A1 (en) * | 1998-04-06 | 1999-10-14 | Fujisawa Pharmaceutical Co., Ltd. | Propanolamine derivatives |
| TW450954B (en) * | 1998-05-14 | 2001-08-21 | Pharmacia & Amp Upjohn Company | Phenylsulfonamide-phenylethylamines useful as dopamine receptors |
| AUPP549998A0 (en) * | 1998-08-26 | 1998-09-17 | Fujisawa Pharmaceutical Co., Ltd. | New compound |
| US6586475B1 (en) * | 1998-11-20 | 2003-07-01 | Takeda Chemical Industries, Ltd. | β-amyloid protein production/secretion inhibitors |
| AU3061499A (en) * | 1998-12-04 | 2000-06-26 | Rimma Iliinichna Ashkinazi | Aryl- and heteroarylamides of carboalkoxysulfanilic acids |
| JP2003055344A (ja) * | 1999-01-29 | 2003-02-26 | Dainippon Pharmaceut Co Ltd | 3,7−ジ置換インドール誘導体及びそれを含有する医薬組成物 |
| WO2001007026A2 (en) * | 1999-07-22 | 2001-02-01 | Eli Lilly And Company | Improved method of treating type ii diabetes and obesity |
| WO2001007025A2 (en) * | 1999-07-22 | 2001-02-01 | Eli Lilly And Company | Treatment of cardiac abnormalities with aryloxy propanolamines |
| EP1214293A1 (de) | 1999-09-08 | 2002-06-19 | Guilford Pharmaceuticals Inc. | Nicht-peptidische cyclophilin bindende verbindungen und ihre verwendung |
| AU7559200A (en) * | 1999-10-12 | 2001-04-23 | Japan Tobacco Inc. | Hypertriglyceridemia remedies and antiobestics |
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| EP0091749A3 (de) * | 1982-04-08 | 1984-12-05 | Beecham Group Plc | Ethanolamin-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen |
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-
1993
- 1993-12-15 US US08/168,105 patent/US5451677A/en not_active Expired - Fee Related
-
1994
- 1994-01-19 WO PCT/US1994/000766 patent/WO1994018161A1/en not_active Ceased
- 1994-02-01 IL IL10850794A patent/IL108507A/en not_active IP Right Cessation
- 1994-02-01 CA CA002114712A patent/CA2114712A1/en not_active Abandoned
- 1994-02-03 EP EP94200303A patent/EP0611003B1/de not_active Expired - Lifetime
- 1994-02-03 ES ES94200303T patent/ES2104259T3/es not_active Expired - Lifetime
- 1994-02-03 DK DK94200303.9T patent/DK0611003T3/da active
- 1994-02-03 AT AT94200303T patent/ATE154594T1/de active
- 1994-02-03 DE DE69403823T patent/DE69403823T2/de not_active Expired - Fee Related
- 1994-02-08 ZA ZA94846A patent/ZA94846B/xx unknown
- 1994-02-08 AU AU54986/94A patent/AU670477B2/en not_active Ceased
- 1994-02-09 JP JP6015323A patent/JP2690006B2/ja not_active Expired - Lifetime
-
1997
- 1997-09-10 GR GR970402315T patent/GR3024672T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO1994018161A1 (en) | 1994-08-18 |
| AU670477B2 (en) | 1996-07-18 |
| ATE154594T1 (de) | 1997-07-15 |
| AU5498694A (en) | 1995-06-29 |
| DK0611003T3 (da) | 1997-08-25 |
| GR3024672T3 (en) | 1997-12-31 |
| ZA94846B (en) | 1994-09-05 |
| IL108507A0 (en) | 1994-05-30 |
| CA2114712A1 (en) | 1994-08-10 |
| EP0611003B1 (de) | 1997-06-18 |
| ES2104259T3 (es) | 1997-10-01 |
| JPH0710827A (ja) | 1995-01-13 |
| JP2690006B2 (ja) | 1997-12-10 |
| EP0611003A1 (de) | 1994-08-17 |
| DE69403823T2 (de) | 1998-01-29 |
| US5451677A (en) | 1995-09-19 |
| DE69403823D1 (de) | 1997-07-24 |
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