IL97424A - שימוש של גואנידין להכנת מוצר תרופתיבעל פעילות נגד נורופפדיד y - Google Patents
שימוש של גואנידין להכנת מוצר תרופתיבעל פעילות נגד נורופפדיד yInfo
- Publication number
- IL97424A IL97424A IL9742491A IL9742491A IL97424A IL 97424 A IL97424 A IL 97424A IL 9742491 A IL9742491 A IL 9742491A IL 9742491 A IL9742491 A IL 9742491A IL 97424 A IL97424 A IL 97424A
- Authority
- IL
- Israel
- Prior art keywords
- pyridin
- propyl
- guanidine
- ethyl
- bromo
- Prior art date
Links
- 150000002357 guanidines Chemical class 0.000 title claims abstract description 10
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 title claims abstract description 10
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 9
- 229940127557 pharmaceutical product Drugs 0.000 title claims description 9
- 238000002360 preparation method Methods 0.000 title claims description 9
- 101710151321 Melanostatin Proteins 0.000 title description 18
- 102400000064 Neuropeptide Y Human genes 0.000 title description 18
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 title description 16
- 230000003042 antagnostic effect Effects 0.000 title description 7
- 206010020772 Hypertension Diseases 0.000 claims abstract description 6
- -1 2- (Diphenylmethoxy) ethyl Chemical group 0.000 claims description 58
- 125000005843 halogen group Chemical group 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 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
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- AKTINKLMHSEEAD-UHFFFAOYSA-N 1-[4-(5-bromo-3-methylpyridin-2-yl)butyl]-2-[3-(1h-imidazol-5-yl)propyl]guanidine Chemical compound CC1=CC(Br)=CN=C1CCCCNC(N)=NCCCC1=CN=CN1 AKTINKLMHSEEAD-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- SHHUUZDGUZDPTA-UHFFFAOYSA-N 1-(3,3-diphenylpropyl)-2-[3-(1h-imidazol-5-yl)propyl]guanidine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)CCNC(=N)NCCCC1=CNC=N1 SHHUUZDGUZDPTA-UHFFFAOYSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- RYYKRNLWXNQBAA-UHFFFAOYSA-N 1-[2-[benzyl-(5-bromo-3-methylpyridin-2-yl)amino]ethyl]-2-[3-(1h-imidazol-5-yl)propyl]guanidine Chemical compound CC1=CC(Br)=CN=C1N(CC=1C=CC=CC=1)CCNC(N)=NCCCC1=CN=CN1 RYYKRNLWXNQBAA-UHFFFAOYSA-N 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- LVCVWKPCWDHJMJ-UHFFFAOYSA-N 1-[3-(3,5-difluorophenyl)-3-pyridin-2-ylpropyl]-1-[3-(1h-imidazol-5-yl)propyl]guanidine Chemical compound C=1C(F)=CC(F)=CC=1C(C=1N=CC=CC=1)CCN(C(=N)N)CCCC1=CN=CN1 LVCVWKPCWDHJMJ-UHFFFAOYSA-N 0.000 claims 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims 2
- HRKLSLHRTZOWMT-UHFFFAOYSA-N 1-(2-benzhydryloxyethyl)-2-[3-(1h-imidazol-5-yl)propyl]guanidine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)OCCNC(=N)NCCCC1=CNC=N1 HRKLSLHRTZOWMT-UHFFFAOYSA-N 0.000 claims 1
- PFZKBUKUGCTUIX-UHFFFAOYSA-N 2-[3-(1h-imidazol-5-yl)propyl]-1-[2-(pyridin-3-ylmethylsulfanyl)ethyl]guanidine Chemical compound C=1C=CN=CC=1CSCCNC(=N)NCCCC1=CNC=N1 PFZKBUKUGCTUIX-UHFFFAOYSA-N 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- 125000005055 alkyl alkoxy group Chemical group 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 238000001704 evaporation Methods 0.000 description 16
- 230000008020 evaporation Effects 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 11
- 235000011167 hydrochloric acid Nutrition 0.000 description 9
- 229960000443 hydrochloric acid Drugs 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 8
- 125000001246 bromo group Chemical group Br* 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 239000011737 fluorine Substances 0.000 description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- UAIGKRVRPAJTNH-UHFFFAOYSA-N 1-(2-benzhydryloxyethyl)-2-[3-(1H-imidazol-5-yl)propyl]guanidine hydroiodide Chemical compound I.C=1C=CC=CC=1C(C=1C=CC=CC=1)OCCN=C(N)NCCCC1=CNC=N1 UAIGKRVRPAJTNH-UHFFFAOYSA-N 0.000 description 2
- AWNVXDSGXRUHRY-UHFFFAOYSA-N 1-[3-(3,5-difluorophenyl)-3-pyridin-2-ylpropyl]-2-[3-(1h-imidazol-5-yl)propyl]guanidine Chemical compound C=1N=CNC=1CCCN=C(N)NCCC(C=1N=CC=CC=1)C1=CC(F)=CC(F)=C1 AWNVXDSGXRUHRY-UHFFFAOYSA-N 0.000 description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CQACNTXCLCGZIQ-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-(2-benzhydryloxyethyl)azanium;iodide Chemical compound [I-].C=1C=CC=CC=1C(OCC[NH+]=C(N)SC)C1=CC=CC=C1 CQACNTXCLCGZIQ-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- HIQJPFXXRFOMBD-UHFFFAOYSA-N 1-[2-[benzyl-(5-bromo-3-methylpyridin-2-yl)amino]ethyl]-2-[3-(1H-imidazol-5-yl)propyl]guanidine trihydrochloride Chemical compound Cl.Cl.Cl.CC1=CC(Br)=CN=C1N(CC=1C=CC=CC=1)CCNC(N)=NCCCC1=CNC=N1 HIQJPFXXRFOMBD-UHFFFAOYSA-N 0.000 description 1
- NQYBOWDUAZYLQK-UHFFFAOYSA-N 1-[3-(3,5-difluorophenyl)-3-pyridin-2-ylpropyl]-2-[3-(1H-imidazol-5-yl)propyl]guanidine trihydrochloride Chemical compound C1=CC=NC(=C1)C(CCNC(=NCCCC2=CN=CN2)N)C3=CC(=CC(=C3)F)F.Cl.Cl.Cl NQYBOWDUAZYLQK-UHFFFAOYSA-N 0.000 description 1
- CLUSMHWEPDXBTI-UHFFFAOYSA-N 2-[3-(1H-imidazol-5-yl)propyl]-1-[2-(pyridin-3-ylmethylsulfanyl)ethyl]guanidine trihydrochloride Chemical compound C1=CC(=CN=C1)CSCCNC(=NCCCC2=CN=CN2)N.Cl.Cl.Cl CLUSMHWEPDXBTI-UHFFFAOYSA-N 0.000 description 1
- VKPJPAPCRZIUMA-UHFFFAOYSA-N 2-[3-(1h-imidazol-5-yl)propyl]guanidine Chemical compound NC(N)=NCCCC1=CN=CN1 VKPJPAPCRZIUMA-UHFFFAOYSA-N 0.000 description 1
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- NFJFUDGBWGXTHS-UHFFFAOYSA-N 2-benzhydryloxyethanamine Chemical compound C=1C=CC=CC=1C(OCCN)C1=CC=CC=C1 NFJFUDGBWGXTHS-UHFFFAOYSA-N 0.000 description 1
- IHDFTEVCMVTMSP-UHFFFAOYSA-N 3-(1h-imidazol-5-yl)propan-1-amine Chemical compound NCCCC1=CN=CN1 IHDFTEVCMVTMSP-UHFFFAOYSA-N 0.000 description 1
- WDSFBMODFMOYJQ-UHFFFAOYSA-N 3-(3,5-difluorophenyl)-3-pyridin-2-ylpropan-1-amine Chemical compound C=1C=CC=NC=1C(CCN)C1=CC(F)=CC(F)=C1 WDSFBMODFMOYJQ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- JELPPOXIPUFDJD-UHFFFAOYSA-N I.BrC=1C=C(C(=NC1)NCCCNC(=NCCCC=1N=CNC1)N)C Chemical compound I.BrC=1C=C(C(=NC1)NCCCNC(=NCCCC=1N=CNC1)N)C JELPPOXIPUFDJD-UHFFFAOYSA-N 0.000 description 1
- NWUKIMKZNVAYOZ-UHFFFAOYSA-N N1=CC(=CC=C1)CSCCNC(N)=N Chemical compound N1=CC(=CC=C1)CSCCNC(N)=N NWUKIMKZNVAYOZ-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000496 cardiotonic agent Substances 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- YFHXZQPUBCBNIP-UHFFFAOYSA-N fura-2 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=3OC(=CC=3C=2)C=2OC(=CN=2)C(O)=O)N(CC(O)=O)CC(O)=O)=C1 YFHXZQPUBCBNIP-UHFFFAOYSA-N 0.000 description 1
- 229910052602 gypsum Inorganic materials 0.000 description 1
- 239000010440 gypsum Substances 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- JBQMUCJXLDIOIF-UHFFFAOYSA-N n-[n'-[3-(1h-imidazol-5-yl)propyl]-n-[2-(pyridin-2-ylamino)ethyl]carbamimidoyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(=NCCCC=1N=CNC=1)NCCNC1=CC=CC=N1 JBQMUCJXLDIOIF-UHFFFAOYSA-N 0.000 description 1
- XPIQAUVQRGTDLF-UHFFFAOYSA-N n-[n-(3,3-diphenylpropyl)-n'-[3-(1h-imidazol-5-yl)propyl]carbamimidoyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(=NCCCC=1NC=NC=1)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 XPIQAUVQRGTDLF-UHFFFAOYSA-N 0.000 description 1
- OCTONKACJKKBBH-UHFFFAOYSA-N n-[n-[4-(5-bromo-3-methylpyridin-2-yl)butyl]-n'-[3-(1h-imidazol-5-yl)propyl]carbamimidoyl]benzamide Chemical compound CC1=CC(Br)=CN=C1CCCCN=C(NC(=O)C=1C=CC=CC=1)NCCCC1=CNC=N1 OCTONKACJKKBBH-UHFFFAOYSA-N 0.000 description 1
- BPGXUIVWLQTVLZ-OFGSCBOVSA-N neuropeptide y(npy) Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 BPGXUIVWLQTVLZ-OFGSCBOVSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP90106200A EP0448765B1 (de) | 1990-03-30 | 1990-03-30 | Verwendung von Guanidinderivaten zur Herstellung eines Arzneimittels mit NPY-antagonistischer Wirkung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL97424A0 IL97424A0 (en) | 1992-06-21 |
| IL97424A true IL97424A (he) | 1995-05-26 |
Family
ID=8203843
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9742491A IL97424A (he) | 1990-03-30 | 1991-03-04 | שימוש של גואנידין להכנת מוצר תרופתיבעל פעילות נגד נורופפדיד y |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0448765B1 (he) |
| JP (1) | JPH0789939A (he) |
| KR (1) | KR910016329A (he) |
| AT (1) | ATE109979T1 (he) |
| AU (1) | AU637882B2 (he) |
| CA (1) | CA2037433A1 (he) |
| DE (1) | DE59006842D1 (he) |
| DK (1) | DK0448765T3 (he) |
| ES (1) | ES2058651T3 (he) |
| HU (1) | HU207945B (he) |
| IE (1) | IE65252B1 (he) |
| IL (1) | IL97424A (he) |
| PT (1) | PT97138A (he) |
| ZA (1) | ZA911471B (he) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2126212A1 (en) * | 1991-12-19 | 1993-07-08 | Albert Tseng | A novel molecule which inhibits neuropeptide tyrosine biological function |
| US5516653A (en) | 1993-12-28 | 1996-05-14 | Synaptic Pharmaceutical Corporation | DNA encoding a human neuropeptide Y/peptide YY/pancreatic polypeptide receptor (Y4) and uses thereof |
| US5545549A (en) * | 1994-02-03 | 1996-08-13 | Synaptic Pharmaceutical Corporation | DNA encoding a human neuropeptide Y/peptide YY (Y2) receptor and uses thereof |
| US5602024A (en) | 1994-12-02 | 1997-02-11 | Synaptic Pharmaceutical Corporation | DNA encoding a hypothalamic atypical neuropeptide Y/peptide YY receptor (Y5) and uses thereof |
| US5989920A (en) * | 1994-12-02 | 1999-11-23 | Synaptic Pharmaceutical Corporation | Methods of modifying feeding behavior compounds useful in such methods and DNA encoding a hypothalmic atypical neuropeptide Y/peptide YY receptor Y5 |
| AU7692996A (en) * | 1995-12-01 | 1997-06-27 | Ciba-Geigy Ag | Receptor antagonists |
| WO1997020822A1 (en) * | 1995-12-01 | 1997-06-12 | Novartis Ag | Quinazolin-2,4-diazirines as npy receptor antagonist |
| EP0912551A1 (en) * | 1996-05-14 | 1999-05-06 | Novo Nordisk A/S | Somatostatin agonists and antagonists |
| US6849733B1 (en) * | 1996-08-23 | 2005-02-01 | Agouron Pharmaceuticals, Inc. | Neuropeptide-Y ligands |
| FR2754709B1 (fr) | 1996-10-23 | 1999-03-05 | Sanofi Sa | Composition cosmetique contenant un antagoniste des recepteurs du neuropeptide gamma et alpha 2 antagonistes susceptibles d'etre incorpores dans une telle composition |
| AU4772497A (en) * | 1996-10-31 | 1998-05-22 | Novo Nordisk A/S | Constrained somatostatin agonists and antagonists |
| JP2000510870A (ja) * | 1997-02-14 | 2000-08-22 | バイエル・コーポレーシヨン | Ｎｐｙ５受容体アンタゴニストとしてのアミド類 |
| US6245817B1 (en) | 1997-02-14 | 2001-06-12 | Bayer Corporation | NPY5 receptor antagonists and methods for using same |
| CA2251368A1 (en) * | 1997-02-14 | 1998-08-20 | Bayer Corporation | Amide derivatives as selective neuropeptide y receptor antagonists |
| US6048900A (en) * | 1998-02-13 | 2000-04-11 | Bayer Corporation | Amide derivatives and methods for using the same as selective neuropeptide Y receptor antagonists |
| US6713265B1 (en) | 1997-06-04 | 2004-03-30 | Synaptic Pharmaceutical Corporation | Methods of modifying feeding behavior, compounds useful in such methods, and DNA encoding a hypothalamic atypical neuropeptide Y/peptide YY receptor (Y5) |
| IL133731A0 (en) | 1997-07-03 | 2001-04-30 | Neurogen Corp | Certain diarylimidazole derivatives, a new class of npy specific ligands |
| ES2161594B1 (es) * | 1998-12-17 | 2003-04-01 | Servier Lab | Nuevos derivados de la hidrazida, su procedimiento de preparacion y las composiciones farmaceuticas que los contienen. |
| WO2000066578A1 (en) | 1999-04-30 | 2000-11-09 | Pfizer Products Inc. | Compounds for the treatment of obesity |
| ES2311544T3 (es) | 2000-09-20 | 2009-02-16 | Schering Corp | Imidazoles sustituidos como agonistas o antagonistas duales de histamina h1 y h3. |
| CN1461304A (zh) | 2000-09-20 | 2003-12-10 | 先灵公司 | 作为双组织胺h1和h3促效剂或拮抗剂的取代的咪唑类化合物 |
| ES2313985T3 (es) | 2000-09-20 | 2009-03-16 | Schering Corporation | Imidazoles sutituidos como agonistas o antagonistas de histamina h1 y h3. |
| CA2421826C (en) | 2000-09-20 | 2009-10-27 | Schering Corporation | Substituted imidazoles as dual histamine h1 and h3 agonists or antagonists |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3579000D1 (de) * | 1985-04-02 | 1990-09-06 | Heumann Pharma Gmbh & Co | Imidazolylalkylguanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel. |
| DE3631334A1 (de) * | 1986-09-15 | 1988-03-17 | Heumann Pharma Gmbh & Co | Neue imidazolylguanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
-
1990
- 1990-03-30 AT AT90106200T patent/ATE109979T1/de active
- 1990-03-30 DE DE59006842T patent/DE59006842D1/de not_active Expired - Fee Related
- 1990-03-30 ES ES90106200T patent/ES2058651T3/es not_active Expired - Lifetime
- 1990-03-30 EP EP90106200A patent/EP0448765B1/de not_active Expired - Lifetime
- 1990-03-30 DK DK90106200.0T patent/DK0448765T3/da active
-
1991
- 1991-02-28 ZA ZA911471A patent/ZA911471B/xx unknown
- 1991-03-01 CA CA002037433A patent/CA2037433A1/en not_active Abandoned
- 1991-03-04 IL IL9742491A patent/IL97424A/he not_active IP Right Cessation
- 1991-03-04 AU AU72068/91A patent/AU637882B2/en not_active Ceased
- 1991-03-25 HU HU91979A patent/HU207945B/hu not_active IP Right Cessation
- 1991-03-25 PT PT97138A patent/PT97138A/pt not_active Application Discontinuation
- 1991-03-26 IE IE99591A patent/IE65252B1/en not_active IP Right Cessation
- 1991-03-26 JP JP3061914A patent/JPH0789939A/ja active Pending
- 1991-03-27 KR KR1019910004812A patent/KR910016329A/ko not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CA2037433A1 (en) | 1991-10-01 |
| HU207945B (en) | 1993-07-28 |
| ATE109979T1 (de) | 1994-09-15 |
| IE65252B1 (en) | 1995-10-18 |
| ZA911471B (en) | 1991-11-27 |
| DE59006842D1 (de) | 1994-09-22 |
| EP0448765A1 (de) | 1991-10-02 |
| IE910995A1 (en) | 1991-10-09 |
| HUT57044A (en) | 1991-11-28 |
| PT97138A (pt) | 1991-11-29 |
| JPH0789939A (ja) | 1995-04-04 |
| AU7206891A (en) | 1991-10-03 |
| ES2058651T3 (es) | 1994-11-01 |
| HU910979D0 (en) | 1991-10-28 |
| DK0448765T3 (da) | 1994-09-19 |
| KR910016329A (ko) | 1991-11-05 |
| EP0448765B1 (de) | 1994-08-17 |
| IL97424A0 (en) | 1992-06-21 |
| AU637882B2 (en) | 1993-06-10 |
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Legal Events
| Date | Code | Title | Description |
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| RH | Patent void |