CA2078058A1 - Imidazo-fused iso- and heterocycles, process for their preparation, compositions containing them and their use - Google Patents

Imidazo-fused iso- and heterocycles, process for their preparation, compositions containing them and their use

Info

Publication number: CA2078058A1
Authority: CA; Canada
Prior art keywords: alkyl; radical; hydrogen; compound; substituted
Prior art date: 1991-09-14
Legal status (The legal status 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 status listed.): Abandoned

Application number

CA002078058A

Other languages

English (en)

French (fr)

Inventor

Holger Heitsch

Adalbert Wagner

Heinz-Werner Kleeman

Hermann Gerhards

Bernward Schoelkens

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Hoechst AG

Original Assignee

Individual

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.)

1991-09-14

Filing date

1992-09-11

Publication date

1993-03-15

1991-09-20 Priority claimed from DE19914131325 external-priority patent/DE4131325A1/de

1992-09-11 Application filed by Individual filed Critical Individual

1993-03-15 Publication of CA2078058A1 publication Critical patent/CA2078058A1/en

Status Abandoned legal-status Critical Current

Links

125000000623 heterocyclic group Chemical group 0.000 title claims abstract description 10
238000000034 method Methods 0.000 title abstract description 41
230000008569 process Effects 0.000 title abstract description 39
239000000203 mixture Substances 0.000 title abstract description 22
238000002360 preparation method Methods 0.000 title abstract description 9
150000001875 compounds Chemical class 0.000 claims abstract description 229
125000006413 ring segment Chemical group 0.000 claims abstract description 19
102000008873 Angiotensin II receptor Human genes 0.000 claims abstract description 4
108050000824 Angiotensin II receptor Proteins 0.000 claims abstract description 4
239000003814 drug Substances 0.000 claims abstract 2
-1 monocyclic radical Chemical class 0.000 claims description 61
150000003254 radicals Chemical class 0.000 claims description 51
239000001257 hydrogen Substances 0.000 claims description 38
229910052739 hydrogen Inorganic materials 0.000 claims description 38
229910052736 halogen Inorganic materials 0.000 claims description 26
150000002367 halogens Chemical class 0.000 claims description 26
150000002431 hydrogen Chemical class 0.000 claims description 25
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
229910052757 nitrogen Inorganic materials 0.000 claims description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
125000004093 cyano group Chemical group *C#N 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 10
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
125000003118 aryl group Chemical group 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 9
239000011737 fluorine Substances 0.000 claims description 9
229910052731 fluorine Inorganic materials 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 9
229920006395 saturated elastomer Polymers 0.000 claims description 9
229910052717 sulfur Inorganic materials 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
125000001072 heteroaryl group Chemical group 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
125000002950 monocyclic group Chemical group 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
125000002619 bicyclic group Chemical group 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 3
230000002152 alkylating effect Effects 0.000 claims description 3
230000003042 antagnostic effect Effects 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
235000010290 biphenyl Nutrition 0.000 claims description 3
239000004305 biphenyl Substances 0.000 claims description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
229910018828 PO3H2 Inorganic materials 0.000 claims description 2
150000005840 aryl radicals Chemical class 0.000 claims description 2
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 2
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 2
125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 2
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 2
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 2
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 12
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 5
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 3
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 2
125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims 1
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims 1
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 1
125000006347 bis(trifluoromethyl)hydroxymethyl group Chemical group [H]OC(*)(C(F)(F)F)C(F)(F)F 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
125000006239 protecting group Chemical group 0.000 claims 1
125000000547 substituted alkyl group Chemical group 0.000 claims 1
125000003396 thiol group Chemical class [H]S* 0.000 claims 1
239000005557 antagonist Substances 0.000 abstract description 3
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 abstract 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 170
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 90
229910052681 coesite Inorganic materials 0.000 description 85
229910052906 cristobalite Inorganic materials 0.000 description 85
239000000377 silicon dioxide Substances 0.000 description 85
235000012239 silicon dioxide Nutrition 0.000 description 85
229910052682 stishovite Inorganic materials 0.000 description 85
229910052905 tridymite Inorganic materials 0.000 description 85
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 68
239000000243 solution Substances 0.000 description 68
238000002844 melting Methods 0.000 description 34
230000008018 melting Effects 0.000 description 34
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 31
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 29
238000006243 chemical reaction Methods 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
238000004587 chromatography analysis Methods 0.000 description 20
229910001868 water Inorganic materials 0.000 description 20
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
238000010265 fast atom bombardment Methods 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
238000010992 reflux Methods 0.000 description 11
239000002904 solvent Substances 0.000 description 11
229950006323 angiotensin ii Drugs 0.000 description 10
229910052786 argon Inorganic materials 0.000 description 10
239000011780 sodium chloride Substances 0.000 description 10
102000005862 Angiotensin II Human genes 0.000 description 9
101800000733 Angiotensin-2 Proteins 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 9
108020003175 receptors Proteins 0.000 description 9
102000005962 receptors Human genes 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
238000009835 boiling Methods 0.000 description 8
238000001816 cooling Methods 0.000 description 8
238000001035 drying Methods 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
125000004076 pyridyl group Chemical group 0.000 description 8
239000007832 Na2SO4 Substances 0.000 description 7
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
235000017550 sodium carbonate Nutrition 0.000 description 7
229910000029 sodium carbonate Inorganic materials 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000002287 radioligand Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
125000004429 atom Chemical group 0.000 description 5
238000006073 displacement reaction Methods 0.000 description 5
239000006260 foam Substances 0.000 description 5
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 5
150000002500 ions Chemical group 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
229910052814 silicon oxide Inorganic materials 0.000 description 5
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 4
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
238000007792 addition Methods 0.000 description 4
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
239000000872 buffer Substances 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
229940125797 compound 12 Drugs 0.000 description 4
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000012528 membrane Substances 0.000 description 4
229910000069 nitrogen hydride Inorganic materials 0.000 description 4
239000012071 phase Substances 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
239000011734 sodium Substances 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
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 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
239000007868 Raney catalyst Substances 0.000 description 3
229910000564 Raney nickel Inorganic materials 0.000 description 3
230000009471 action Effects 0.000 description 3
210000004100 adrenal gland Anatomy 0.000 description 3
HXBPYFMVGFDZFT-UHFFFAOYSA-N allyl isocyanate Chemical compound C=CCN=C=O HXBPYFMVGFDZFT-UHFFFAOYSA-N 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
HEGXUBFMGZWSNA-UHFFFAOYSA-N amino 3-nitrobenzoate Chemical compound NOC(=O)C1=CC=CC([N+]([O-])=O)=C1 HEGXUBFMGZWSNA-UHFFFAOYSA-N 0.000 description 3
XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000013078 crystal Substances 0.000 description 3
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
239000003480 eluent Substances 0.000 description 3
239000008103 glucose Substances 0.000 description 3
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
238000011534 incubation Methods 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
238000005259 measurement Methods 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
235000015320 potassium carbonate Nutrition 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000000700 radioactive tracer Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 2
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
VVQNAFBGAWCMLU-UHFFFAOYSA-N 1h-benzimidazole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1N=CN2 VVQNAFBGAWCMLU-UHFFFAOYSA-N 0.000 description 2
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
101800000734 Angiotensin-1 Proteins 0.000 description 2
102400000344 Angiotensin-1 Human genes 0.000 description 2
108010039627 Aprotinin Proteins 0.000 description 2
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
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IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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210000003368 zona glomerulosa Anatomy 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
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Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Detergent Compositions (AREA)
Lubricants (AREA)
Pyridine Compounds (AREA)

CA002078058A 1991-09-14 1992-09-11 Imidazo-fused iso- and heterocycles, process for their preparation, compositions containing them and their use Abandoned CA2078058A1 (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DE4130659		1991-09-14
DEP4130659.7		1991-09-14
DEP4131325.9		1991-09-20
DE19914131325 DE4131325A1 (de)	1991-09-20	1991-09-20	Imidazo-annellierte iso und heterocyclen, verfahren zu deren herstellung, sie enthaltende mittel und ihre verwendung

Publications (1)

Publication Number	Publication Date
CA2078058A1 true CA2078058A1 (en)	1993-03-15

Family

ID=25907347

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002078058A Abandoned CA2078058A1 (en)	1991-09-14	1992-09-11	Imidazo-fused iso- and heterocycles, process for their preparation, compositions containing them and their use

Country Status (22)

Country	Link
US (2)	US5444068A (2)
EP (1)	EP0533058B1 (2)
JP (1)	JP3459659B2 (2)
KR (1)	KR930006020A (2)
CN (1)	CN1070646A (2)
AT (1)	ATE247644T1 (2)
AU (1)	AU659485B2 (2)
BR (1)	BR9203543A (2)
CA (1)	CA2078058A1 (2)
CZ (1)	CZ280492A3 (2)
DE (1)	DE59209986D1 (2)
DK (1)	DK0533058T3 (2)
ES (1)	ES2204888T3 (2)
FI (1)	FI924054L (2)
HU (1)	HUT62892A (2)
IL (1)	IL103141A0 (2)
NO (1)	NO300326B1 (2)
NZ (1)	NZ244303A (2)
PL (1)	PL171766B1 (2)
PT (1)	PT533058E (2)
RU (1)	RU2076105C1 (2)
TW (1)	TW300219B (2)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5571813A (en) *	1993-06-10	1996-11-05	Beiersdorf-Lilly Gmbh	Fused pyrimidine compounds and their use as pharmaceuticals
US5714508A (en) *	1993-08-05	1998-02-03	Roussel Uclaf	Bicycle Derivatives of imidazole
US6316637B1 (en)	1994-08-04	2001-11-13	Synaptic Pharmaceutical Corporation	Benzimidazole derivatives
US6495583B1 (en)	1997-03-25	2002-12-17	Synaptic Pharmaceutical Corporation	Benzimidazole derivatives

Families Citing this family (59)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5223499A (en) *	1989-05-30	1993-06-29	Merck & Co., Inc.	6-amino substituted imidazo[4,5-bipyridines as angiotensin II antagonists
US5210092A (en) *	1990-09-25	1993-05-11	Fujisawa Pharmaceutical Co., Ltd.	Angiotensin ii antagonizing heterocyclic derivatives
CA2062558A1 (en) *	1991-03-08	1992-09-09	Prasun K. Chakravarty	Heterocyclic compounds bearing acidic functional groups as angiotensin ii antagonists
SK2895A3 (en) *	1992-07-10	1995-07-11	Boots Co Plc	Substituted 3-cyclobutene-1,2-diones, method of their preparation and pharmaceutical agents which containing thereof
TW348175B (en) *	1993-01-06	1998-12-21	Hoechst Ag	Process for the preparation of biphenyl derivatives
CA2125251C (en) *	1993-06-07	2005-04-26	Yoshiyuki Inada	A pharmaceutical composition for angiotensin ii-mediated diseases
EP0628559B1 (en) *	1993-06-10	2002-04-03	Beiersdorf-Lilly GmbH	Pyrimidine compounds and their use as pharmaceuticals
DE4320432A1 (de) *	1993-06-21	1994-12-22	Bayer Ag	Substituierte Mono- und Bipyridylmethylderivate
US6122929A (en) *	1996-12-18	2000-09-26	Showa Aluminum Corporation	Accumulator
RU2222534C2 (ru) *	1997-04-24	2004-01-27	Орто-Макнейл Фармасьютикал, Инк.	Замещенные имидазолы, способ их получения, фармацевтическая композиция на их основе, способы лечения цитокин-опосредованных заболеваний
PL337888A1 (en)	1997-07-03	2000-09-11	Du Pont Pharm Co	Imidazoprimidines and imidazopyridines for use in treating neurological disorders
SK7792000A3 (en) *	1997-11-24	2001-01-18	Procter & Gamble	5-(2-imidazolinylamino)-benzimidazole derivatives, their preparation and their use as alpha-adrenoceptor agonists with improved metabolic stability
US6365589B1 (en)	1998-07-02	2002-04-02	Bristol-Myers Squibb Pharma Company	Imidazo-pyridines, -pyridazines, and -triazines as corticotropin releasing factor antagonists
US6124463A (en) *	1998-07-02	2000-09-26	Dupont Pharmaceuticals	Benzimidazoles as corticotropin release factor antagonists
US20050267148A1 (en) *	1998-07-15	2005-12-01	Teijin Limited	Benzimidazole derivative
AU758789B2 (en) *	1998-07-15	2003-03-27	Teijin Limited	Thiobenzimidazole derivatives
WO2000019156A1 (en) *	1998-09-29	2000-04-06	Stanhope Products Company	Self-positioning adsorbent package for air conditioning accumulators
US6331539B1 (en) *	1999-06-10	2001-12-18	3M Innovative Properties Company	Sulfonamide and sulfamide substituted imidazoquinolines
US6279341B1 (en) *	1999-07-01	2001-08-28	Multisorb Technologies, Inc.	Self-retaining adsorbent unit
GB9919778D0 (en) *	1999-08-21	1999-10-27	Zeneca Ltd	Chemical compounds
WO2001053272A1 (en) *	2000-01-17	2001-07-26	Teijin Limited	Human chymase inhibitors
WO2003064414A1 (en) *	2002-01-29	2003-08-07	Vicore Pharma Ab.	Tricyclic compounds useful as angiotensin ii agonists
HRP20050248A2 (en) *	2002-09-17	2005-10-31	Warner-Lambert Company Llc	Heterocyclic substituted piperazines for the treatment of schizophrenia
US20040102360A1 (en) *	2002-10-30	2004-05-27	Barnett Stanley F.	Combination therapy
BRPI0413558A (pt)	2003-08-12	2006-10-17	3M Innovative Properties Co	compostos contendo imidazo substituìdo por hidroxilamina
MXPA06002199A (es)	2003-08-27	2006-05-22	3M Innovative Properties Co	Imidazoquinolinas sustituidas con grupos ariloxi o arilalquilenoxi.
CA2537763A1 (en)	2003-09-05	2005-03-17	3M Innovative Properties Company	Treatment for cd5+ b cell lymphoma
CA2540541C (en)	2003-10-03	2012-03-27	3M Innovative Properties Company	Alkoxy substituted imidazoquinolines
US7544697B2 (en)	2003-10-03	2009-06-09	Coley Pharmaceutical Group, Inc.	Pyrazolopyridines and analogs thereof
US7897767B2 (en)	2003-11-14	2011-03-01	3M Innovative Properties Company	Oxime substituted imidazoquinolines
WO2005048945A2 (en)	2003-11-14	2005-06-02	3M Innovative Properties Company	Hydroxylamine substituted imidazo ring compounds
WO2005051317A2 (en)	2003-11-25	2005-06-09	3M Innovative Properties Company	Substituted imidazo ring systems and methods
JP2007517035A (ja)	2003-12-29	2007-06-28	スリーエムイノベイティブプロパティズカンパニー	アリールアルケニルおよびアリールアルキニル置換されたイミダゾキノリン
EP1699788A2 (en)	2003-12-30	2006-09-13	3M Innovative Properties Company	Imidazoquinolinyl, imidazopyridinyl and imidazonaphthyridinyl sulfonamides
WO2005094531A2 (en)	2004-03-24	2005-10-13	3M Innovative Properties Company	Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines
US8017779B2 (en)	2004-06-15	2011-09-13	3M Innovative Properties Company	Nitrogen containing heterocyclyl substituted imidazoquinolines and imidazonaphthyridines
US8026366B2 (en)	2004-06-18	2011-09-27	3M Innovative Properties Company	Aryloxy and arylalkyleneoxy substituted thiazoloquinolines and thiazolonaphthyridines
US7897609B2 (en)	2004-06-18	2011-03-01	3M Innovative Properties Company	Aryl substituted imidazonaphthyridines
US7915281B2 (en)	2004-06-18	2011-03-29	3M Innovative Properties Company	Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and method
JP5543068B2 (ja)	2004-12-30	2014-07-09	スリーエムイノベイティブプロパティズカンパニー	キラル縮合［１，２］イミダゾ［４，５−ｃ］環状化合物
AU2005326708C1 (en)	2004-12-30	2012-08-30	3M Innovative Properties Company	Substituted chiral fused [1,2]imidazo[4,5-c] ring compounds
WO2006084251A2 (en)	2005-02-04	2006-08-10	Coley Pharmaceutical Group, Inc.	Aqueous gel formulations containing immune reponse modifiers
CA2597587A1 (en)	2005-02-11	2006-08-17	Coley Pharmaceutical Group, Inc.	Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods
JP2008538550A (ja)	2005-04-01	2008-10-30	コーリーファーマシューティカルグループ，インコーポレイテッド	ウイルス感染および腫瘍性疾患を処置するためのサイトカイン生合成の調節因子としての１−置換ピラゾロ（３，４−ｃ）環状化合物
JP2008535832A (ja)	2005-04-01	2008-09-04	コーリーファーマシューティカルグループ，インコーポレイテッド	ピラゾロピリジン−１，４−ジアミン、およびそのアナログ
US7906506B2 (en)	2006-07-12	2011-03-15	3M Innovative Properties Company	Substituted chiral fused [1,2] imidazo [4,5-c] ring compounds and methods
US8969514B2 (en)	2007-06-04	2015-03-03	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
EP2527360B1 (en)	2007-06-04	2015-10-28	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EP2810951B1 (en)	2008-06-04	2017-03-15	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EP3241839B1 (en)	2008-07-16	2019-09-04	Bausch Health Ireland Limited	Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
CA2905438A1 (en)	2013-03-15	2014-09-25	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase and their uses
CA2905435A1 (en)	2013-03-15	2014-09-25	Synergy Pharmaceuticals Inc.	Compositions useful for the treatment of gastrointestinal disorders
SI3004138T1 (sl)	2013-06-05	2024-07-31	Bausch Health Ireland Limited	Ultra čisti agonisti gvanilat ciklaze C, postopek za njihovo pripravo in uporabo
WO2016100184A1 (en)	2014-12-16	2016-06-23	Forum Pharmaceuticals, Inc.	Geminal substituted quinuclidine amide compounds as agonists of alpha-7 nicotinic acetylcholine receptors
MX2017016231A (es)	2015-06-10	2018-11-29	Axovant Sciences Gmbh	Compuestos de aminobencisoxazol como agonistas de receptores a7-nicotínicos de acetilcolina.
WO2017027600A1 (en)	2015-08-12	2017-02-16	Forum Pharmaceuticals, Inc.	GEMINAL SUBSTITUTED AMINOBENZISOXAZOLE COMPOUNDS AS AGONISTS OF α7-NICOTINIC ACETYLCHOLINE RECEPTORS
KR102419223B1 (ko) *	2021-11-16	2022-07-08	세진산업(주)	수소유기균열 방지를 위한 초고압 배관
KR102643639B1 (ko) *	2023-02-20	2024-03-05	(주) 범강기연	무용접 가스 파이프 연결 구조 및 방법

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4612323A (en) *	1983-06-27	1986-09-16	Sumitomo Chemical Company, Limited	Insecticidal and acaricidal derivatives of 1-benzylbenzimidazole
IT1173196B (it) *	1984-02-02	1987-06-18	Bellon Roger Schoum Rbs Pharma	Composti imidazopiridinici farmacologicamente attivi
JPS61151176A (ja) *	1984-12-24	1986-07-09	Sumitomo Chem Co Ltd	ベンズイミダゾール誘導体およびそれを有効成分とする殺虫、殺ダニ剤
US4728741A (en) *	1985-01-08	1988-03-01	Smithkline Beckman Corporation	1-substituted-2-mercapto benzimidazole compounds and intermediates
US4880804A (en) *	1988-01-07	1989-11-14	E. I. Du Pont De Nemours And Company	Angiotensin II receptor blocking benzimidazoles
JPH0273071A (ja) *	1988-09-09	1990-03-13	Sumitomo Chem Co Ltd	ベンズイミダゾール誘導体、その製造法およびそれを有効成分とする殺虫、殺ダニ剤
GB8904174D0 (en) *	1989-02-23	1989-04-05	British Bio Technology	Compounds
DE3928177A1 (de) *	1989-04-08	1991-02-28	Thomae Gmbh Dr K	Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
EP0400835A1 (en) *	1989-05-15	1990-12-05	Merck & Co. Inc.	Substituted benzimidazoles as angiotensin II antagonists
IE64514B1 (en) *	1989-05-23	1995-08-09	Zeneca Ltd	Azaindenes
GB8911854D0 (en) *	1989-05-23	1989-07-12	Ici Plc	Heterocyclic compounds
US5102880A (en) *	1989-05-30	1992-04-07	Merck & Co., Inc.	Substituted imidazo-fused 6-membered heterocycles as angiotensin II antagonists
US5223499A (en) *	1989-05-30	1993-06-29	Merck & Co., Inc.	6-amino substituted imidazo[4,5-bipyridines as angiotensin II antagonists
IL94390A (en) *	1989-05-30	1996-03-31	Merck & Co Inc	The 6-membered trans-nitrogen-containing heterocycles are compressed with imidazo and pharmaceutical preparations containing them
IE70593B1 (en) *	1989-09-29	1996-12-11	Eisai Co Ltd	Biphenylmethane derivative the use of it and pharmacological compositions containing same
US5298518A (en) *	1989-09-29	1994-03-29	Eisai Co., Ltd.	Biphenylmethane derivative and pharmacological use
IL95975A (en) *	1989-10-24	1997-06-10	Takeda Chemical Industries Ltd	N-benzyl- 2-alkylbenzimidazole derivatives, their production and pharmaceutical compositions containing them
GB8927277D0 (en) *	1989-12-01	1990-01-31	Glaxo Group Ltd	Chemical compounds
EP0430709A3 (en) *	1989-12-01	1992-02-12	Glaxo Group Limited	Benzthiophen derivatives
FR2658511B1 (fr) *	1990-02-16	1992-06-19	Union Pharma Scient Appl	Nouveaux derives de benzimidazole et d'azabenzimidazole, antagonistes des recepteurs au thromboxane; leurs procedes de preparation, compositions pharmaceutiques les contenant.
ES2121773T3 (es) *	1990-06-08	1998-12-16	Hoechst Marion Roussel Inc	Derivados de bencimidazol, su procedimiento de preparacion, productos intermedios, su aplicacion como medicamentos y composiciones farmaceuticas que los contienen.
AU653524B2 (en) *	1990-06-08	1994-10-06	Roussel-Uclaf	New imidazole derivatives, their preparation process, the new intermediates obtained, their use as medicaments and the pharmaceutical compositions containing them
EP0470543A1 (de) *	1990-08-10	1992-02-12	Dr. Karl Thomae GmbH	Heterocyclische Imidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zur ihrer Herstellung
DE4025359A1 (de) *	1990-08-10	1992-02-13	Triumph Adler Ag	Verfahren zur einstellung der abdruckenergie einer type und schreibmaschine, drucker o. dgl. zur durchfuehrung des verfahrens
US5087702A (en) *	1991-01-30	1992-02-11	Merck & Co., Inc.	Microbial transformation process for producing an antihypertensive product
US5177074A (en) *	1991-03-26	1993-01-05	Merck & Co., Inc.	Angiotensin ii antagonists incorporating a substituted thiophene or furan
US5158327A (en) *	1991-10-11	1992-10-27	Neil Rowe	Hydraulic hose coupling handle and method of making same
US5376666A (en) *	1992-11-30	1994-12-27	The Du Pont Merck Pharmaceutical Company	Angiotension-II receptor blocking, azacycloalkyl or azacycloalkenyl
DE4304455A1 (de) *	1993-02-15	1994-08-18	Bayer Ag	Heterocyclisch substituierte Phenyl-cyclohexan-carbonsäurederivate
US5395844A (en) *	1993-06-10	1995-03-07	The Du Pont Merck Pharmaceutical Company	Imidazole 5-position substituted angiotensin II antagonists

1992
- 1992-03-07 TW TW081101731A patent/TW300219B/zh active
- 1992-09-10 AT AT92115500T patent/ATE247644T1/de active
- 1992-09-10 ES ES92115500T patent/ES2204888T3/es not_active Expired - Lifetime
- 1992-09-10 FI FI924054A patent/FI924054L/fi not_active Application Discontinuation
- 1992-09-10 PT PT92115500T patent/PT533058E/pt unknown
- 1992-09-10 EP EP92115500A patent/EP0533058B1/de not_active Expired - Lifetime
- 1992-09-10 DE DE59209986T patent/DE59209986D1/de not_active Expired - Lifetime
- 1992-09-10 DK DK92115500T patent/DK0533058T3/da active
- 1992-09-11 BR BR929203543A patent/BR9203543A/pt not_active Application Discontinuation
- 1992-09-11 JP JP24346992A patent/JP3459659B2/ja not_active Expired - Lifetime
- 1992-09-11 RU SU925053022A patent/RU2076105C1/ru active
- 1992-09-11 AU AU23533/92A patent/AU659485B2/en not_active Ceased
- 1992-09-11 CA CA002078058A patent/CA2078058A1/en not_active Abandoned
- 1992-09-11 CZ CS922804A patent/CZ280492A3/cs unknown
- 1992-09-11 IL IL103141A patent/IL103141A0/xx unknown
- 1992-09-11 NO NO923535A patent/NO300326B1/no unknown
- 1992-09-11 NZ NZ244303A patent/NZ244303A/en unknown
- 1992-09-11 PL PL92295911A patent/PL171766B1/pl unknown
- 1992-09-12 CN CN92110562A patent/CN1070646A/zh active Pending
- 1992-09-14 KR KR1019920016634A patent/KR930006020A/ko not_active Ceased
- 1992-09-14 HU HU9202931A patent/HUT62892A/hu unknown
1993
- 1993-12-13 US US08/165,655 patent/US5444068A/en not_active Expired - Lifetime
1995
- 1995-06-05 US US08/463,299 patent/US5635525A/en not_active Expired - Lifetime

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5571813A (en) *	1993-06-10	1996-11-05	Beiersdorf-Lilly Gmbh	Fused pyrimidine compounds and their use as pharmaceuticals
US5602137A (en) *	1993-06-10	1997-02-11	Beiersdorf-Lilly Gmbh	Pyrimidine compounds and their use as pharmaceuticals
US5602136A (en) *	1993-06-10	1997-02-11	Beiersdorf-Lilly Gmbh	Pyrimidine compounds and their use as pharmaceuticals
US5714508A (en) *	1993-08-05	1998-02-03	Roussel Uclaf	Bicycle Derivatives of imidazole
US6316637B1 (en)	1994-08-04	2001-11-13	Synaptic Pharmaceutical Corporation	Benzimidazole derivatives
US6403626B1 (en)	1994-08-04	2002-06-11	Synaptic Pharmaceutical Corporation	Benzimidazole derivatives
US6495583B1 (en)	1997-03-25	2002-12-17	Synaptic Pharmaceutical Corporation	Benzimidazole derivatives

Also Published As

Publication number	Publication date
AU659485B2 (en)	1995-05-18
AU2353392A (en)	1993-03-18
PL295911A1 (en)	1993-03-22
NO923535D0 (no)	1992-09-11
EP0533058A1 (de)	1993-03-24
PT533058E (pt)	2004-01-30
US5635525A (en)	1997-06-03
CZ280492A3 (en)	1993-04-14
HUT62892A (en)	1993-06-28
NO923535L (no)	1993-03-15
DK0533058T3 (da)	2003-11-24
CN1070646A (zh)	1993-04-07
NO300326B1 (no)	1997-05-12
KR930006020A (ko)	1993-04-20
IL103141A0 (en)	1993-02-21
EP0533058B1 (de)	2003-08-20
PL171766B1 (pl)	1997-06-30
BR9203543A (pt)	1993-04-13
US5444068A (en)	1995-08-22
NZ244303A (en)	1995-12-21
TW300219B (2)	1997-03-11
FI924054A0 (fi)	1992-09-10
JP3459659B2 (ja)	2003-10-20
JPH05262742A (ja)	1993-10-12
FI924054A7 (fi)	1993-03-15
DE59209986D1 (de)	2003-09-25
ATE247644T1 (de)	2003-09-15
HU9202931D0 (en)	1992-11-30
FI924054L (fi)	1993-03-15
RU2076105C1 (ru)	1997-03-27
ES2204888T3 (es)	2004-05-01

Legal Events

Date	Code	Title	Description
2000-09-11	FZDE	Discontinued

Publication	Publication Date	Title
CA2078058A1 (en)	1993-03-15	Imidazo-fused iso- and heterocycles, process for their preparation, compositions containing them and their use
US5225414A (en)	1993-07-06	Substituted azoles, a process for their preparation, and their use
US5350751A (en)	1994-09-27	Substituted imidazoles, pharmaceutical compositions containing these, and the use thereof as antagonists of angiotensin II receptors for the treatment of high blood pressure
US5338740A (en)	1994-08-16	Angiotensin II receptor antagonists
US5604251A (en)	1997-02-18	Imidazole derivatives with a biphenylsulfonylurea or biphenylsulfonylurethane side chain and their use as angitensin II receptors
JPH04308587A (ja)	1992-10-30	イミダゾ−ル誘導体およびその製法
CA2026533A1 (en)	1991-03-30	Biphenylmethane derivative and pharmacological use
RU2190612C2 (ru)	2002-10-10	Новые производные индол-2,3-дион-3-оксима
US5510354A (en)	1996-04-23	Imidazopyridine derivatives
IE913991A1 (en)	1992-05-20	Substituted azoles, process for their preparation, agents¹containing them and their use
HUT62576A (en)	1993-05-28	Process for producing substituted imidazolylpropenoic acid derivatives and pharmaceutical compositions comprising such compounds
HUT62578A (en)	1993-05-28	Process for producing cyclic group-substituted imidazolylpropenoic acid derivatives and pharmaceutical compositions comprising such compounds
IL103021A (en)	1996-10-16	2-alkyl-1- (OR3)-biphenylylmethyl-imidazoindolizinone derivatives their preparation and pharmaceutical compositions containing them
JPH02200685A (ja)	1990-08-08	新規なインドール誘導体
JPH02233682A (ja)	1990-09-17	８，９―アヌレーション化―１，２，３，４―テトラヒドロ―β―カルボリン誘導体
JPS6284A (ja)	1987-01-06	イミダゾキノリン抗血栓性強心薬
CA2252116A1 (en)	1997-10-30	N-3 substituted pyrimidin-4-ones with aii antagonistic activity
DE4131325A1 (de)	1993-04-01	Imidazo-annellierte iso und heterocyclen, verfahren zu deren herstellung, sie enthaltende mittel und ihre verwendung