IL98794A - 4-alkyl-2-propyl-1-[(2'-(1h-tetrazol-5-yl) biphenyl-4-yl)-methyl]-imidazole derivatives and pharmaceutical compositions containing them - Google Patents

4-alkyl-2-propyl-1-[(2'-(1h-tetrazol-5-yl) biphenyl-4-yl)-methyl]-imidazole derivatives and pharmaceutical compositions containing them

Info

Publication number: IL98794A
Authority: IL; Israel
Prior art keywords: propyl; ethyl; methyl; compounds; compound
Prior art date: 1990-07-13

Application number

IL9879491A

Other languages

English (en)

Other versions

IL98794A0 (en

Original Assignee

Du Pont

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.)

1990-07-13

Filing date

1991-07-11

Publication date

1995-11-27

1991-07-11 Application filed by Du Pont filed Critical Du Pont

1992-07-15 Publication of IL98794A0 publication Critical patent/IL98794A0/xx

1995-11-27 Publication of IL98794A publication Critical patent/IL98794A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 9
239000002220 antihypertensive agent Substances 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 30
238000000034 method Methods 0.000 claims description 7
206010020772 Hypertension Diseases 0.000 claims description 6
241001465754 Metazoa Species 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 3
230000036772 blood pressure Effects 0.000 claims description 2
229940123413 Angiotensin II antagonist Drugs 0.000 abstract description 3
239000002333 angiotensin II receptor antagonist Substances 0.000 abstract description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
239000000243 solution Substances 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000000047 product Substances 0.000 description 12
239000004480 active ingredient Substances 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
239000000203 mixture Substances 0.000 description 8
239000007787 solid Substances 0.000 description 8
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000002904 solvent Substances 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
239000002775 capsule Substances 0.000 description 5
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
239000012267 brine Substances 0.000 description 4
238000001816 cooling Methods 0.000 description 4
239000003814 drug Substances 0.000 description 4
238000010828 elution Methods 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
150000002460 imidazoles Chemical class 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
239000000725 suspension Substances 0.000 description 4
PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 3
206010007559 Cardiac failure congestive Diseases 0.000 description 3
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
206010019280 Heart failures Diseases 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
230000003276 anti-hypertensive effect Effects 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
238000004440 column chromatography Methods 0.000 description 3
229910052802 copper Inorganic materials 0.000 description 3
239000010949 copper Substances 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
-1 imidazole aldehydes Chemical class 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000008297 liquid dosage form Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
GFAZHVHNLUBROE-UHFFFAOYSA-N 1-hydroxybutan-2-one Chemical compound CCC(=O)CO GFAZHVHNLUBROE-UHFFFAOYSA-N 0.000 description 2
ZOMATQMEHRJKLO-UHFFFAOYSA-N 1h-imidazol-2-ylmethanol Chemical class OCC1=NC=CN1 ZOMATQMEHRJKLO-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
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 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
229940030600 antihypertensive agent Drugs 0.000 description 2
239000011260 aqueous acid Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000007891 compressed tablet Substances 0.000 description 2
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
239000003182 parenteral nutrition solution Substances 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 2
239000008096 xylene Substances 0.000 description 2
VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
KYWMCFOWDYFYLV-UHFFFAOYSA-N 1h-imidazole-2-carboxylic acid Chemical class OC(=O)C1=NC=CN1 KYWMCFOWDYFYLV-UHFFFAOYSA-N 0.000 description 1
ZTFVTXDWDFIQEU-UHFFFAOYSA-N 5-[2-[4-(bromomethyl)phenyl]phenyl]-1-trityltetrazole Chemical group C1=CC(CBr)=CC=C1C1=CC=CC=C1C1=NN=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ZTFVTXDWDFIQEU-UHFFFAOYSA-N 0.000 description 1
MVWLYVZXKXPSLQ-UHFFFAOYSA-N 5-ethyl-2-propyl-1h-imidazole Chemical compound CCCC1=NC(CC)=CN1 MVWLYVZXKXPSLQ-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
101800000734 Angiotensin-1 Proteins 0.000 description 1
102400000344 Angiotensin-1 Human genes 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
238000006951 Weidenhagen imidazole synthesis reaction Methods 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I 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)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000003064 anti-oxidating effect Effects 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
238000004040 coloring Methods 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
238000011049 filling Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000007789 gas Substances 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
230000000004 hemodynamic effect Effects 0.000 description 1
230000009097 homeostatic mechanism Effects 0.000 description 1
229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
238000007031 hydroxymethylation reaction Methods 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
239000000463 material Substances 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
PUMCQAGLTAGULO-UHFFFAOYSA-N methyl pent-2-ynoate Chemical compound CCC#CC(=O)OC PUMCQAGLTAGULO-UHFFFAOYSA-N 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
235000019629 palatability Nutrition 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
LZTRCELOJRDYMQ-UHFFFAOYSA-N triphenylmethanol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)C1=CC=CC=C1 LZTRCELOJRDYMQ-UHFFFAOYSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
235000012141 vanillin Nutrition 0.000 description 1
239000008215 water for injection Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives

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Animal Behavior & Ethology (AREA)
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Veterinary Medicine (AREA)
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Bioinformatics & Cheminformatics (AREA)
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Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Lubricants (AREA)
Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
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Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

IL9879491A 1990-07-13 1991-07-11 4-alkyl-2-propyl-1-[(2'-(1h-tetrazol-5-yl) biphenyl-4-yl)-methyl]-imidazole derivatives and pharmaceutical compositions containing them IL98794A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US55263790A	1990-07-13	1990-07-13
US07/650,258 US5137902A (en)	1990-07-13	1991-02-04	4-alkylimidazole derivatives and anti-hypertensive use thereof

Publications (2)

Publication Number	Publication Date
IL98794A0 IL98794A0 (en)	1992-07-15
IL98794A true IL98794A (en)	1995-11-27

Family

ID=27070086

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9879491A IL98794A (en)	1990-07-13	1991-07-11	4-alkyl-2-propyl-1-[(2'-(1h-tetrazol-5-yl) biphenyl-4-yl)-methyl]-imidazole derivatives and pharmaceutical compositions containing them

Country Status (23)

Country	Link
US (1)	US5137902A (pl)
EP (1)	EP0539509B1 (pl)
JP (1)	JP2550455B2 (pl)
KR (1)	KR0162669B1 (pl)
AT (1)	ATE121087T1 (pl)
AU (1)	AU639400B2 (pl)
BG (1)	BG61341B1 (pl)
CA (1)	CA2087274C (pl)
CZ (1)	CZ280018B6 (pl)
DE (1)	DE69108913T2 (pl)
DK (1)	DK0539509T3 (pl)
ES (1)	ES2071325T3 (pl)
FI (1)	FI102752B1 (pl)
HU (2)	HUT63411A (pl)
IE (1)	IE69849B1 (pl)
IL (1)	IL98794A (pl)
MY (1)	MY140243A (pl)
NO (1)	NO303015B1 (pl)
NZ (1)	NZ238920A (pl)
PL (1)	PL168311B1 (pl)
RO (1)	RO111270B1 (pl)
SK (1)	SK279326B6 (pl)
WO (1)	WO1992000977A2 (pl)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
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US5616599A (en) *	1991-02-21	1997-04-01	Sankyo Company, Limited	Angiotensin II antagosist 1-biphenylmethylimidazole compounds and their therapeutic use
DE4132633A1 (de) *	1991-10-01	1993-04-08	Bayer Ag	Cyclisch substituierte imidazolyl-propensaeurederivate
US5250558A (en) *	1992-01-28	1993-10-05	Merck & Co., Inc.	Substituted triazolinones, triazolinethiones, and triazolinimines as neurotensin antagonists used to treat psychosis
WO1993017681A1 (en) *	1992-03-02	1993-09-16	Abbott Laboratories	Angiotensin ii receptor antagonists
GB9218449D0 (en)	1992-08-29	1992-10-14	Boots Co Plc	Therapeutic agents
US5310929A (en) *	1992-08-06	1994-05-10	E. I. Du Pont De Nemours And Company	Prodrugs of imidazole carboxylic acids as angiotensin II receptor antagonists
JP3501484B2 (ja) *	1992-12-17	2004-03-02	三共株式会社	ビフェニル誘導体
US5338740A (en) *	1993-07-13	1994-08-16	Pfizer Inc.	Angiotensin II receptor antagonists
SE9903028D0 (sv)	1999-08-27	1999-08-27	Astra Ab	New use
AU2001267404A1 (en) *	2000-05-04	2001-11-12	Ipf Pharmaceuticals Gmbh	Novel compounds for the treatment of inflammatory and cardiovascular diseases
CA2568640C (en)	2004-06-04	2011-08-09	Teva Pharmaceutical Industries Ltd.	Pharmaceutical composition containing irbesartan
WO2006029057A1 (en) *	2004-09-02	2006-03-16	Teva Pharmaceutical Industries, Ltd.	Purification of olmesartan medoxomil
US20070054948A1 (en) *	2004-09-02	2007-03-08	Lilach Hedvati	Purification of olmesartan medoxomil
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
MX2009013293A (es)	2007-06-04	2010-02-15	Synergy Pharmaceuticals Inc	Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos.
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
CA2730603C (en)	2008-07-16	2019-09-24	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, 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
JP2016514671A (ja)	2013-03-15	2016-05-23	シナジーファーマシューティカルズインコーポレイテッド	グアニル酸シクラーゼのアゴニストおよびその使用
JP2016514670A (ja)	2013-03-15	2016-05-23	シナジーファーマシューティカルズインコーポレイテッド	他の薬物と組み合わせたグアニル酸シクラーゼ受容体アゴニスト
EA201592263A1 (ru)	2013-06-05	2016-05-31	Синерджи Фармасьютикалз, Инк.	Ультрачистые агонисты гуанилатциклазы c, способ их получения и использования

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4820843A (en) *	1987-05-22	1989-04-11	E. I. Du Pont De Nemours And Company	Tetrazole intermediates to antihypertensive compounds
US5015651A (en) *	1988-01-07	1991-05-14	E. I. Du Pont De Nemours And Company	Treatment of hypertension with 1,2,4-angiotensin II antagonists
US4880804A (en) *	1988-01-07	1989-11-14	E. I. Du Pont De Nemours And Company	Angiotensin II receptor blocking benzimidazoles
CA1338238C (en) *	1988-01-07	1996-04-09	David John Carini	Angiotensin ii receptor blocking imidazoles and combinations thereof with diuretics and nsaids
US5064825A (en) *	1989-06-01	1991-11-12	Merck & Co., Inc.	Angiotensin ii antagonists
HU217958B (hu) *	1989-06-30	2000-05-28	E. I. Du Pont De Nemours And Co.	Helyettesített imidazolszármazékok, ezeket tartalmazó gyógyszerkészítmények és eljárás előállításukra
EP0479892A1 (en) *	1989-06-30	1992-04-15	E.I. Du Pont De Nemours And Company	Fused-ring aryl substituted imidazoles
DE4132633A1 (de) *	1991-10-01	1993-04-08	Bayer Ag	Cyclisch substituierte imidazolyl-propensaeurederivate

1991
- 1991-02-04 US US07/650,258 patent/US5137902A/en not_active Expired - Lifetime
- 1991-07-11 IL IL9879491A patent/IL98794A/en not_active IP Right Cessation
- 1991-07-11 NZ NZ238920A patent/NZ238920A/en not_active IP Right Cessation
- 1991-07-12 IE IE243891A patent/IE69849B1/en not_active IP Right Cessation
- 1991-07-12 MY MYPI91001263A patent/MY140243A/en unknown
- 1991-07-15 CZ CS923912A patent/CZ280018B6/cs not_active IP Right Cessation
- 1991-07-15 ES ES91914167T patent/ES2071325T3/es not_active Expired - Lifetime
- 1991-07-15 SK SK3912-92A patent/SK279326B6/sk not_active IP Right Cessation
- 1991-07-15 HU HU924058A patent/HUT63411A/hu unknown
- 1991-07-15 AU AU83116/91A patent/AU639400B2/en not_active Expired
- 1991-07-15 KR KR1019930700076A patent/KR0162669B1/ko not_active Expired - Lifetime
- 1991-07-15 CA CA002087274A patent/CA2087274C/en not_active Expired - Lifetime
- 1991-07-15 DK DK91914167.1T patent/DK0539509T3/da active
- 1991-07-15 DE DE69108913T patent/DE69108913T2/de not_active Expired - Lifetime
- 1991-07-15 HU HU9204058A patent/HU223530B1/hu active IP Right Grant
- 1991-07-15 JP JP3513329A patent/JP2550455B2/ja not_active Expired - Lifetime
- 1991-07-15 WO PCT/US1991/004826 patent/WO1992000977A2/en not_active Ceased
- 1991-07-15 EP EP91914167A patent/EP0539509B1/en not_active Expired - Lifetime
- 1991-07-15 PL PL91297616A patent/PL168311B1/pl unknown
- 1991-07-15 RO RO93-00803A patent/RO111270B1/ro unknown
- 1991-07-15 AT AT91914167T patent/ATE121087T1/de not_active IP Right Cessation
1993
- 1993-01-11 NO NO930088A patent/NO303015B1/no not_active IP Right Cessation
- 1993-01-12 FI FI930109A patent/FI102752B1/fi not_active IP Right Cessation
- 1993-02-11 BG BG97438A patent/BG61341B1/bg unknown

Also Published As

Publication number	Publication date
DE69108913T2 (de)	1995-08-24
EP0539509B1 (en)	1995-04-12
NO303015B1 (no)	1998-05-18
JP2550455B2 (ja)	1996-11-06
SK279326B6 (sk)	1998-10-07
EP0539509A1 (en)	1993-05-05
AU8311691A (en)	1992-02-04
PL168311B1 (pl)	1996-02-29
CA2087274A1 (en)	1992-01-14
FI102752B (fi)	1999-02-15
FI930109L (fi)	1993-01-12
HU223530B1 (hu)	2004-08-30
PL297616A1 (pl)	1992-07-13
ES2071325T3 (es)	1995-06-16
IE912438A1 (en)	1992-01-15
IL98794A0 (en)	1992-07-15
FI930109A0 (fi)	1993-01-12
CZ280018B6 (cs)	1995-09-13
BG61341B1 (en)	1997-06-30
RO111270B1 (ro)	1996-08-30
IE69849B1 (en)	1996-10-02
MY140243A (en)	2009-12-31
AU639400B2 (en)	1993-07-22
HUT63411A (en)	1993-08-30
KR0162669B1 (ko)	1998-12-01
WO1992000977A2 (en)	1992-01-23
NZ238920A (en)	1993-07-27
ATE121087T1 (de)	1995-04-15
CZ391292A3 (en)	1993-12-15
JPH05508415A (ja)	1993-11-25
DE69108913D1 (de)	1995-05-18
SK391292A3 (en)	1993-07-07
DK0539509T3 (da)	1995-07-03
CA2087274C (en)	2002-02-19
HU9204058D0 (en)	1993-03-29
FI102752B1 (fi)	1999-02-15
NO930088D0 (no)	1993-01-11
BG97438A (bg)	1994-03-24
WO1992000977A3 (en)	1992-02-20
US5137902A (en)	1992-08-11
NO930088L (no)	1993-01-11

Legal Events

Date	Code	Title
1996-05-14	FF	Patent granted
1997-11-20	KB	Patent renewed
2001-10-31	KB	Patent renewed
2005-09-25	KB	Patent renewed
2010-02-14	KB	Patent renewed
2012-02-29	EXP	Patent expired

Publication	Publication Date	Title
EP0539509B1 (en)	1995-04-12	4-alkylimidazole derivatives
JPH05507713A (ja)	1993-11-04	置換ベンズイミダゾール、その製造方法およびその薬学的使用
US6465505B1 (en)	2002-10-15	Benzyl-substituted benzimidazoles
HU193348B (en)	1987-09-28	Process for producing piroxicam salts of antiflogistic activity
US9079876B2 (en)	2015-07-14	Imidazole derivatives and preparation method and use thereof
JP4837722B2 (ja)	2011-12-14	置換スルホキシド化合物、その調製方法、およびその使用方法
EP0238753B1 (en)	1992-01-15	N-substituted condensed polymethylene imine derivatives
JPS6233172A (ja)	1987-02-13	ド−パミン−β−ヒドロキシラ−ゼ抑制剤
JPS60501207A (ja)	1985-08-01	化合物
JPS62230788A (ja)	1987-10-09	抗潰瘍剤としての２−〔（２−ピリジル）メチルスルフイニル〕チエノイミダゾ−ル類
JPH0680041B2 (ja)	1994-10-12	２−ピリジル酢酸誘導体、その製法およびそれを含む医薬
JP3032844B2 (ja)	2000-04-17	ピリミジンジオン誘導体
HU210071A9 (hu)	1995-02-28	4-Alkil-imidazoi-származékok és azok vérnyomáscsökkentőként történő alkalmazása
KR100487029B1 (ko)	2005-11-25	신규화합물
JPH0673008A (ja)	1994-03-15	アンジオテンシンｉｉ拮抗性ピリジン誘導体
WO2000031071A1 (en)	2000-06-02	2-alkyl-5-halo-3-[2'-(tetrazol-5-yl)-biphenyl-4-ylmethyl]-3h-imidazole-4-carboxaldehyde acetal derivatives, their preparation and use
HK1240590A1 (en)	2018-05-25	Bifunctional compounds and use for reducing uric acid levels
ZA200303891B (en)	2004-05-20	Ethanolates of sodium-hydrogen exchanger type-1 inhibitor.
RU2000116627A (ru)	2002-06-10	Новые соединения, обладающие ингибирующим действием в отношении сgmp-pde
CA2340168A1 (en)	2000-02-24	N-substituted azabicycloheptane derivatives, production and use thereof