IL97424A - Use of guanidine for the preparation of a medicinal product with anti-neuropfed Y activity - Google Patents

Use of guanidine for the preparation of a medicinal product with anti-neuropfed Y activity

Info

Publication number: IL97424A
Authority: IL; Israel
Prior art keywords: pyridin; propyl; guanidine; ethyl; bromo
Prior art date: 1990-03-30

Application number

IL9742491A

Other languages

English (en)

Hebrew (he)

Other versions

IL97424A0 (en

Original Assignee

Heumann Pharma Gmbh & Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-03-30

Filing date

1991-03-04

Publication date

1995-05-26

1991-03-04 Application filed by Heumann Pharma Gmbh & Co filed Critical Heumann Pharma Gmbh & Co

1992-06-21 Publication of IL97424A0 publication Critical patent/IL97424A0/xx

1995-05-26 Publication of IL97424A publication Critical patent/IL97424A/en

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)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Plural Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)

IL9742491A 1990-03-30 1991-03-04 Use of guanidine for the preparation of a medicinal product with anti-neuropfed Y activity IL97424A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP90106200A EP0448765B1 (fr)	1990-03-30	1990-03-30	Uitlisation de dérivés de la guanidine pour la fabrication d'un médicament à activité antagoniste du neuropeptide Y

Publications (2)

Publication Number	Publication Date
IL97424A0 IL97424A0 (en)	1992-06-21
IL97424A true IL97424A (en)	1995-05-26

Family

ID=8203843

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9742491A IL97424A (en)	1990-03-30	1991-03-04	Use of guanidine for the preparation of a medicinal product with anti-neuropfed Y activity

Country Status (14)

Country	Link
EP (1)	EP0448765B1 (fr)
JP (1)	JPH0789939A (fr)
KR (1)	KR910016329A (fr)
AT (1)	ATE109979T1 (fr)
AU (1)	AU637882B2 (fr)
CA (1)	CA2037433A1 (fr)
DE (1)	DE59006842D1 (fr)
DK (1)	DK0448765T3 (fr)
ES (1)	ES2058651T3 (fr)
HU (1)	HU207945B (fr)
IE (1)	IE65252B1 (fr)
IL (1)	IL97424A (fr)
PT (1)	PT97138A (fr)
ZA (1)	ZA911471B (fr)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0672054A4 (fr) *	1991-12-19	1996-02-07	Garvan Inst Med Res	Nouvelle molecule inhibant la fonction biologique du neuropeptide tyrosine.
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
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
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
AU7692996A (en) *	1995-12-01	1997-06-27	Ciba-Geigy Ag	Receptor antagonists
AU7692896A (en) *	1995-12-01	1997-06-27	Novartis Ag	Quinazolin-2,4-diazirines as NPY receptor antagonist
ZA974147B (en) *	1996-05-14	1997-11-14	Novo Nordisk As	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
ZA979701B (en) *	1996-10-31	1998-05-21	Novo Nordisk As Novo Nordisk A	Constrained somatostatin agonists and antagonists.Constrained somatostatin agonists and 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
CA2251580A1 (fr) *	1997-02-14	1998-08-20	Bayer Corporation	Amides utilises comme antagonistes du recepteur de npy5
US6245817B1 (en)	1997-02-14	2001-06-12	Bayer Corporation	NPY5 receptor antagonists and methods for using same
EP0910565A1 (fr) *	1997-02-14	1999-04-28	Bayer Corporation	Derives amides actifs comme antagonistes selectifs du recepteur du neuropeptide y
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)
KR20010020610A (ko)	1997-07-03	2001-03-15	해피 페너 ; 해리 에이치. 페너 2세	엔피와이 특이적 리간드 유형인 디아릴이미다졸 유도체
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.
AU2935200A (en)	1999-04-30	2000-11-17	Pfizer Products Inc.	Compounds for the treatment of obesity
US6506756B2 (en)	2000-09-20	2003-01-14	Schering Corporation	Substituted imidazoles as dual histamine H1 and H3 agonists or antagonists
ES2311544T3 (es)	2000-09-20	2009-02-16	Schering Corp	Imidazoles sustituidos como agonistas o antagonistas duales de histamina h1 y h3.
ES2313985T3 (es) *	2000-09-20	2009-03-16	Schering Corporation	Imidazoles sutituidos como agonistas o antagonistas de histamina h1 y h3.
JP2004514709A (ja)	2000-09-20	2004-05-20	シェーリング　コーポレイション	ヒスタミンｈ１およびｈ３の二重アゴニストまたは二重アンタゴニストとしての置換イミダゾール

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0199845B1 (fr) *	1985-04-02	1990-08-01	HEUMANN PHARMA GMBH & CO	Dérivés d'imidazolylalkylguanidine, leur procédé de préparation et compositions les contenant
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 DE DE59006842T patent/DE59006842D1/de not_active Expired - Fee Related
- 1990-03-30 EP EP90106200A patent/EP0448765B1/fr not_active Expired - Lifetime
- 1990-03-30 DK DK90106200.0T patent/DK0448765T3/da active
- 1990-03-30 AT AT90106200T patent/ATE109979T1/de active
- 1990-03-30 ES ES90106200T patent/ES2058651T3/es not_active Expired - Lifetime
1991
- 1991-02-28 ZA ZA911471A patent/ZA911471B/xx unknown
- 1991-03-01 CA CA002037433A patent/CA2037433A1/fr not_active Abandoned
- 1991-03-04 IL IL9742491A patent/IL97424A/en 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 JP JP3061914A patent/JPH0789939A/ja active Pending
- 1991-03-26 IE IE99591A patent/IE65252B1/en not_active IP Right Cessation
- 1991-03-27 KR KR1019910004812A patent/KR910016329A/ko not_active Ceased

Also Published As

Publication number	Publication date
ES2058651T3 (es)	1994-11-01
HU207945B (en)	1993-07-28
IL97424A0 (en)	1992-06-21
ZA911471B (en)	1991-11-27
AU7206891A (en)	1991-10-03
JPH0789939A (ja)	1995-04-04
DE59006842D1 (de)	1994-09-22
IE65252B1 (en)	1995-10-18
HU910979D0 (en)	1991-10-28
AU637882B2 (en)	1993-06-10
EP0448765A1 (fr)	1991-10-02
DK0448765T3 (da)	1994-09-19
HUT57044A (en)	1991-11-28
PT97138A (pt)	1991-11-29
EP0448765B1 (fr)	1994-08-17
KR910016329A (ko)	1991-11-05
CA2037433A1 (fr)	1991-10-01
ATE109979T1 (de)	1994-09-15
IE910995A1 (en)	1991-10-09

Legal Events

Date	Code	Title	Description
1998-02-22	RH	Patent void

Publication	Publication Date	Title
IL97424A (en)	1995-05-26	Use of guanidine for the preparation of a medicinal product with anti-neuropfed Y activity
AU2005297966B2 (en)	2010-12-23	Amorphous object of cinnamide compound
CS244423B2 (en)	1986-07-17	Method of substituted 1,2-diaminocyclobuten-3,4-dions production
KR960009570B1 (ko)	1996-07-20	이미다졸린 유도체 및 그의 제조방법
US4912119A (en)	1990-03-27	Imidazolylguanidine derivatives and compositions containing these compounds
FI70580C (fi)	1986-09-24	Foerfarande foer framstaellning av terapeutiskt anvaendbara n-(4-/i 3-staellning substituerad pyridyl/-piperatzinyl)alk ylazaspirodecandioner
US9090624B2 (en)	2015-07-28	Aromatic bycyclic derivatives as CXCR4 receptor modulators
DE3782621T2 (de)	1993-04-22	Imidazol-derivate, verfahren zu ihrer herstellung, pharmazeutische zubereitungen, welche diese enthalten, verwendung dieser zur herstellung therapeutisch wirksamer arzneimittel und zwischenprodukte, welche beim herstellungsverfahren entstehen.
EP0441226A1 (fr)	1991-08-14	(cyanométhyl)pyridines utiles comme antagonistes du PAF
JPS62252780A (ja)	1987-11-04	新規なインデノチアゾ−ル誘導体及びその製造法
US5212187A (en)	1993-05-18	Pyridyl alkylamine compounds which are useful against histamine h1 and h2 receptors
CN101177385B (zh)	2011-06-15	芳基磺酰胺及其类似物及其在治疗神经变性疾病中的用途
JPS63270678A (ja)	1988-11-08	新規含窒素化合物
KR100248643B1 (ko)	2000-07-01	아릴 및 헤테로아릴 알콕시나프탈렌 유도체
EP0105702B1 (fr)	1986-06-25	Composés de dioxocyclobutène
DE69805033T2 (de)	2002-11-14	Tetrazolderivate als LTD4 und H1 Antagonisten
KR880002209B1 (ko)	1988-10-18	치환된 3,4-디아미노-1,2,5-티아디아졸류 및 그의 제조방법
RU2143429C1 (ru)	1999-12-27	ПРОИЗВОДНЫЕ 6-(2-ИМИДАЗОЛИНИЛАМИНО)ХИНОЛИНА И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ, ОБЛАДАЮЩАЯ АНТАГОНИСТИЧЕСКОЙ АКТИВНОСТЬЮ В ОТНОШЕНИИ α--2-АДРЕНОРЕЦЕПТОРОВ
US4948802A (en)	1990-08-14	Guanidine carboxylic acid esters and pharmaceutical preparations containing these compounds
US4772704A (en)	1988-09-20	2,5-disubstituted-4(3H)-pyrimidones having histamine H2 -receptor antagonist activity
US4590192A (en)	1986-05-20	Benzisothiazoles, their pharmaceutical compositions, and method of use
HK1112738B (en)	2012-03-23	Arylsulfonamides and analogues as well as use for the treatment of neuro-degenerative disorders
HK1097820B (en)	2009-01-23	Aryl sulfonamides and analogues thereof and their use in the treatment of neurodegenerative diseases
JPWO1998032742A1 (ja)	2000-05-30	新規なアミド誘導体及びその医薬組成物