IL103021A - 2-alkyl-1- (OR3)-biphenylylmethyl-imidazoindolizinone derivatives their preparation and pharmaceutical compositions containing them - Google Patents

2-alkyl-1- (OR3)-biphenylylmethyl-imidazoindolizinone derivatives their preparation and pharmaceutical compositions containing them

Info

Publication number: IL103021A
Authority: IL; Israel
Prior art keywords: group; mixture; methyl; substituted; biphenyl
Prior art date: 1991-09-10

Application number

IL10302192A

Other languages

English (en)

Other versions

IL103021A0 (en

Original Assignee

Tanabe Seiyaku 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.)

1991-09-10

Filing date

1992-09-02

Publication date

1996-10-16

1992-09-02 Application filed by Tanabe Seiyaku Co filed Critical Tanabe Seiyaku Co

1993-02-21 Publication of IL103021A0 publication Critical patent/IL103021A0/xx

1996-10-16 Publication of IL103021A publication Critical patent/IL103021A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 3
238000002360 preparation method Methods 0.000 title abstract description 6
150000003839 salts Chemical class 0.000 claims abstract description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 15
125000000217 alkyl group Chemical group 0.000 claims abstract description 15
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 10
ZTJVDMYOVFOUDV-UHFFFAOYSA-N 5h-imidazo[4,5-g]indolizine Chemical class C1C=C2N=CN=C2C2=CC=CN12 ZTJVDMYOVFOUDV-UHFFFAOYSA-N 0.000 claims abstract description 9
125000002252 acyl group Chemical group 0.000 claims abstract description 8
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 8
125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 6
125000005129 aryl carbonyl group Chemical group 0.000 claims abstract description 6
125000002915 carbonyl group Chemical class [*:2]C([*:1])=O 0.000 claims abstract description 5
206010020772 Hypertension Diseases 0.000 claims abstract description 4
-1 carboxyphenyl group Chemical group 0.000 claims description 58
150000001875 compounds Chemical class 0.000 claims description 38
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
125000006239 protecting group Chemical group 0.000 claims description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims description 7
125000003831 tetrazolyl group Chemical group 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 4
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
125000000068 chlorophenyl group Chemical group 0.000 claims description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
206010011416 Croup infectious Diseases 0.000 claims 5
201000010549 croup Diseases 0.000 claims 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 1
239000003085 diluting agent Substances 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
229940043274 prophylactic drug Drugs 0.000 claims 1
102000005862 Angiotensin II Human genes 0.000 abstract description 6
101800000733 Angiotensin-2 Proteins 0.000 abstract description 6
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 abstract description 6
229950006323 angiotensin ii Drugs 0.000 abstract description 6
238000000034 method Methods 0.000 abstract description 4
238000011282 treatment Methods 0.000 abstract description 3
239000001257 hydrogen Substances 0.000 abstract description 2
229910052739 hydrogen Inorganic materials 0.000 abstract description 2
230000002401 inhibitory effect Effects 0.000 abstract description 2
238000011321 prophylaxis Methods 0.000 abstract description 2
239000000203 mixture Substances 0.000 description 102
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 94
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
239000002904 solvent Substances 0.000 description 72
239000000047 product Substances 0.000 description 67
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
239000000243 solution Substances 0.000 description 52
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
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 45
238000006243 chemical reaction Methods 0.000 description 33
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
101150041968 CDC13 gene Proteins 0.000 description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
125000004432 carbon atom Chemical group C* 0.000 description 25
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 25
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
239000006260 foam Substances 0.000 description 24
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
229940093499 ethyl acetate Drugs 0.000 description 20
235000019439 ethyl acetate Nutrition 0.000 description 20
238000010898 silica gel chromatography Methods 0.000 description 20
239000000843 powder Substances 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000003921 oil Substances 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 15
239000012044 organic layer Substances 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
238000001816 cooling Methods 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
239000002585 base Substances 0.000 description 11
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 10
229910052783 alkali metal Inorganic materials 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000012267 brine Substances 0.000 description 9
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 8
239000010410 layer Substances 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
229940086542 triethylamine Drugs 0.000 description 8
ABWMZAYOVKWWHF-UHFFFAOYSA-N [Na].[Na].C1=CCN2C=CC(C=C12)=O Chemical compound [Na].[Na].C1=CCN2C=CC(C=C12)=O ABWMZAYOVKWWHF-UHFFFAOYSA-N 0.000 description 7
238000004440 column chromatography Methods 0.000 description 7
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
SXDFLWCFMHRIJN-UHFFFAOYSA-N [Na].[Na].C=1C=CN2CC(C=CC12)=O Chemical compound [Na].[Na].C=1C=CN2CC(C=CC12)=O SXDFLWCFMHRIJN-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
ZTFVTXDWDFIQEU-UHFFFAOYSA-N 5-[2-[4-(bromomethyl)phenyl]phenyl]-1-trityltetrazole Chemical compound 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 5
238000001914 filtration Methods 0.000 description 5
239000007858 starting material Substances 0.000 description 5
HGINADPHJQTSKN-UHFFFAOYSA-N Monoethyl malonic acid Chemical compound CCOC(=O)CC(O)=O HGINADPHJQTSKN-UHFFFAOYSA-N 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 4
239000011347 resin Substances 0.000 description 4
229920005989 resin Polymers 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
CLWNFISSJZXCJH-UHFFFAOYSA-N 2-[2-propyl-1-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]ethanamine;hydrochloride Chemical compound Cl.CCCC1=NC(CCN)=CN1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 CLWNFISSJZXCJH-UHFFFAOYSA-N 0.000 description 3
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
239000002220 antihypertensive agent Substances 0.000 description 3
239000004305 biphenyl Substances 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
238000004821 distillation Methods 0.000 description 3
239000003814 drug Substances 0.000 description 3
WQDAFQAEXDFZTP-UHFFFAOYSA-N ethyl 2-oxoacetate;hydrate Chemical compound O.CCOC(=O)C=O WQDAFQAEXDFZTP-UHFFFAOYSA-N 0.000 description 3
KWFADUNOPOSMIJ-UHFFFAOYSA-N ethyl 3-chloro-3-oxopropanoate Chemical compound CCOC(=O)CC(Cl)=O KWFADUNOPOSMIJ-UHFFFAOYSA-N 0.000 description 3
230000001077 hypotensive effect Effects 0.000 description 3
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
SFNCYGRQJHHJAJ-UHFFFAOYSA-N methyl 2-butyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate Chemical compound CCCCC1=NC=2CCNC(C(=O)OC)C=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 SFNCYGRQJHHJAJ-UHFFFAOYSA-N 0.000 description 3
239000004533 oil dispersion Substances 0.000 description 3
MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 3
235000006408 oxalic acid Nutrition 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000000725 suspension Substances 0.000 description 3
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
TUCQOIQFSKJKPH-UHFFFAOYSA-N (2-propyl-1h-imidazol-5-yl)methanol Chemical compound CCCC1=NC(CO)=CN1 TUCQOIQFSKJKPH-UHFFFAOYSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
XLLSLEQKJDTBLZ-UHFFFAOYSA-N 2-[2-propyl-1-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]ethanamine Chemical compound CCCC1=NC(CCN)=CN1CC1=CC=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 XLLSLEQKJDTBLZ-UHFFFAOYSA-N 0.000 description 2
NHZLCNSYWKPLOI-UHFFFAOYSA-N 2-butyl-5-(chloromethyl)-1h-imidazole;hydrochloride Chemical compound Cl.CCCCC1=NC(CCl)=CN1 NHZLCNSYWKPLOI-UHFFFAOYSA-N 0.000 description 2
CVLPUQBROLPQKC-UHFFFAOYSA-N 3h-indolizin-7-one Chemical compound O=C1C=CN2CC=CC2=C1 CVLPUQBROLPQKC-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
238000010533 azeotropic distillation Methods 0.000 description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
235000010290 biphenyl Nutrition 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
238000010531 catalytic reduction reaction Methods 0.000 description 2
ISOLMABRZPQKOV-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate Chemical compound CCOC(=O)C(NC(C)=O)C(=O)OCC ISOLMABRZPQKOV-UHFFFAOYSA-N 0.000 description 2
WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
UFJKDHMPTBTUGM-UHFFFAOYSA-N ethyl 2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate Chemical compound CCCC1=NC=2CCNC(C(=O)OCC)C=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 UFJKDHMPTBTUGM-UHFFFAOYSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 2
125000001841 imino group Chemical group [H]N=* 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
239000007788 liquid Substances 0.000 description 2
JADXGOGYSFSUCG-UHFFFAOYSA-N methyl 2-butyl-1-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-6-carboxylate Chemical compound CCCCC1=NC=2CNC(C(=O)OC)CC=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 JADXGOGYSFSUCG-UHFFFAOYSA-N 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
UZKBZGAMRJRWLR-UHFFFAOYSA-N (2-butyl-1H-imidazol-4-yl)methanol Chemical compound CCCCC1=NC=C(CO)N1 UZKBZGAMRJRWLR-UHFFFAOYSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
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XIXAZYJFXKGALX-UHFFFAOYSA-N methyl 2-[4-[[4-(2-aminoethyl)-2-butylimidazol-1-yl]methyl]phenyl]benzoate;hydrochloride Chemical compound Cl.CCCCC1=NC(CCN)=CN1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 XIXAZYJFXKGALX-UHFFFAOYSA-N 0.000 description 1
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HLSMDKYPHMEPLI-UHFFFAOYSA-N tert-butyl n-[2-(2-butyl-1h-imidazol-5-yl)ethyl]carbamate Chemical compound CCCCC1=NC(CCNC(=O)OC(C)(C)C)=CN1 HLSMDKYPHMEPLI-UHFFFAOYSA-N 0.000 description 1
FRSOAIPXCHNMGL-UHFFFAOYSA-N tert-butyl n-[2-[2-butyl-3-(methoxymethyl)imidazol-4-yl]ethyl]carbamate Chemical compound CCCCC1=NC=C(CCNC(=O)OC(C)(C)C)N1COC FRSOAIPXCHNMGL-UHFFFAOYSA-N 0.000 description 1
QKPMQYPSMQVJKP-UHFFFAOYSA-N tert-butyl n-[2-[3-(methoxymethyl)imidazol-4-yl]ethyl]carbamate Chemical compound COCN1C=NC=C1CCNC(=O)OC(C)(C)C QKPMQYPSMQVJKP-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-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
238000005406 washing Methods 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1

Classifications

- 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
- 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
- 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
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)

IL10302192A 1991-09-10 1992-09-02 2-alkyl-1- (OR3)-biphenylylmethyl-imidazoindolizinone derivatives their preparation and pharmaceutical compositions containing them IL103021A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP30856091		1991-09-10
JP5304492		1992-01-27

Publications (2)

Publication Number	Publication Date
IL103021A0 IL103021A0 (en)	1993-02-21
IL103021A true IL103021A (en)	1996-10-16

Family

ID=26393753

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10302192A IL103021A (en)	1991-09-10	1992-09-02	2-alkyl-1- (OR3)-biphenylylmethyl-imidazoindolizinone derivatives their preparation and pharmaceutical compositions containing them

Country Status (16)

Country	Link
US (1)	US5268377A (de)
EP (1)	EP0531876B1 (de)
JP (1)	JP2590797B2 (de)
KR (1)	KR0168457B1 (de)
AT (1)	ATE146474T1 (de)
AU (1)	AU644539B2 (de)
CA (1)	CA2077420C (de)
DE (1)	DE69216013T2 (de)
DK (1)	DK0531876T3 (de)
ES (1)	ES2098403T3 (de)
FI (1)	FI98369C (de)
GR (1)	GR3022106T3 (de)
ID (1)	ID902B (de)
IL (1)	IL103021A (de)
MY (1)	MY129927A (de)
SG (1)	SG42962A1 (de)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH06271576A (ja) *	1993-03-19	1994-09-27	Upjohn Co:The	イミダゾール誘導体の製法
FR2712592B1 (fr) *	1993-11-17	1995-12-22	Adir	Nouveaux dérivés tricycliques azotés, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
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
WO2008151257A2 (en)	2007-06-04	2008-12-11	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
ES2627848T3 (es)	2008-06-04	2017-07-31	Synergy Pharmaceuticals Inc.	Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos
ES2624828T3 (es)	2008-07-16	2017-07-17	Synergy Pharmaceuticals Inc.	Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
EP2968439A2 (de)	2013-03-15	2016-01-20	Synergy Pharmaceuticals Inc.	Zusammensetzungen zur behandlung von magen-darm-störungen
US9708367B2 (en)	2013-03-15	2017-07-18	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase and their uses
PL3004138T3 (pl)	2013-06-05	2024-07-29	Bausch Health Ireland Limited	Ultra-oczyszczeni agoniści peptydowi cyklazy guanylanowej C, sposób ich uzyskiwania i ich zastosowanie
BR112018077075A2 (pt)	2016-06-29	2019-04-30	Universite De Montreal	heterociclos de biarilmetila

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SU1047148A1 (ru) *	1981-03-30	1986-12-23	Институт физико-органической химии и углехимии АН УССР	Бензилиденпроизводные имидазо-[4,5-L]-индолизинов,обладающие бактериостатической и фунгистатической активностью
US4686226A (en) *	1985-09-03	1987-08-11	Merck & Co., Inc.	Substituted benzo[b]furo- and benzo[b]thieno quinolizines
US4812462A (en) *	1986-04-01	1989-03-14	Warner-Lambert Company	4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid analogs having antihypertensive activity
US4816463A (en) *	1986-04-01	1989-03-28	Warner-Lambert Company	Substituted diimidazo [1,5-a: 4',5'-d]pyridines having antihypertensive activity
CA1334092C (en) *	1986-07-11	1995-01-24	David John Carini	Angiotensin ii receptor blocking imidazoles
DE3928177A1 (de) *	1989-04-08	1991-02-28	Thomae Gmbh Dr K	Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
IL96019A0 (en) *	1989-10-31	1991-07-18	Fujisawa Pharmaceutical Co	Imidazole derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same

1992
- 1992-09-02 AT AT92114987T patent/ATE146474T1/de not_active IP Right Cessation
- 1992-09-02 IL IL10302192A patent/IL103021A/en not_active IP Right Cessation
- 1992-09-02 CA CA002077420A patent/CA2077420C/en not_active Expired - Fee Related
- 1992-09-02 SG SG1996001486A patent/SG42962A1/en unknown
- 1992-09-02 AU AU22056/92A patent/AU644539B2/en not_active Ceased
- 1992-09-02 DE DE69216013T patent/DE69216013T2/de not_active Expired - Fee Related
- 1992-09-02 ES ES92114987T patent/ES2098403T3/es not_active Expired - Lifetime
- 1992-09-02 DK DK92114987.8T patent/DK0531876T3/da active
- 1992-09-02 EP EP92114987A patent/EP0531876B1/de not_active Expired - Lifetime
- 1992-09-03 US US07/939,652 patent/US5268377A/en not_active Expired - Fee Related
- 1992-09-07 MY MYPI92001597A patent/MY129927A/en unknown
- 1992-09-08 KR KR1019920016409A patent/KR0168457B1/ko not_active Expired - Fee Related
- 1992-09-08 JP JP4239080A patent/JP2590797B2/ja not_active Expired - Lifetime
- 1992-09-10 ID IDP469892A patent/ID902B/id unknown
- 1992-09-10 FI FI924043A patent/FI98369C/fi active
1996
- 1996-12-19 GR GR960403177T patent/GR3022106T3/el unknown

Also Published As

Publication number	Publication date
JPH05279365A (ja)	1993-10-26
FI98369C (fi)	1997-06-10
DE69216013D1 (de)	1997-01-30
ID902B (id)	1996-09-09
KR930006024A (ko)	1993-04-20
CA2077420A1 (en)	1993-03-11
EP0531876A2 (de)	1993-03-17
US5268377A (en)	1993-12-07
FI924043A0 (fi)	1992-09-10
AU2205692A (en)	1993-03-11
JP2590797B2 (ja)	1997-03-12
FI924043L (fi)	1993-03-11
DE69216013T2 (de)	1997-05-07
IL103021A0 (en)	1993-02-21
ES2098403T3 (es)	1997-05-01
MY129927A (en)	2007-05-31
SG42962A1 (en)	1997-10-17
EP0531876A3 (de)	1993-05-05
DK0531876T3 (de)	1997-02-17
CA2077420C (en)	1998-08-25
ATE146474T1 (de)	1997-01-15
AU644539B2 (en)	1993-12-09
EP0531876B1 (de)	1996-12-18
KR0168457B1 (ko)	1999-01-15
FI98369B (fi)	1997-02-28
GR3022106T3 (en)	1997-03-31

Legal Events

Date	Code	Title
1997-03-18	FF	Patent granted
1997-07-13	KB	Patent renewed
1999-01-26	KB	Patent renewed
2003-06-24	RH1	Patent not in force

Publication	Publication Date	Title
US5424316A (en)	1995-06-13	Imidazopyridine derivatives for the treatment of hypertension
EP1572113B1 (de)	2017-05-17	Calcium-rezeptor-modulierende verbindung und ihre verwendung
CZ292544B6 (cs)	2003-10-15	Deriváty 1H-imidazopyridinu a léčiva na jejich bázi
WO2003053926A1 (en)	2003-07-03	Novel phenylalanine derivative
EP0531876B1 (de)	1996-12-18	Imidazoindolizinderivate mit Angiotensin-II Hemmwirkung
IE58115B1 (en)	1993-07-14	New beta -carboline-3-oxadiazolyl derivatives,method of preparing the same and their use
US5281613A (en)	1994-01-25	Heterocyclic compounds
CA2119095A1 (en)	1994-09-19	Heterotricyclically substituted phenyl-cyclohexane-carboxylic acid derivatives
EP0812838A1 (de)	1997-12-17	Pyridoncarbonsäurederivate substituiert von bicyclischer aminogruppe, deren ester und salze, und bicyclisches amin als zwischenprodukt davon
US6080756A (en)	2000-06-27	Polymorphs of the prodrug 6-N-(L-ALA-L-ALA)-trovafloxacin
JP2564784B2 (ja)	1996-12-18	イミダゾピリジン誘導体及びその製法
EP0682023B1 (de)	1997-02-12	Imidazopyridin-Derivate und Verfahren zu ihrer Herstellung
JPH06312927A (ja)	1994-11-08	アンジオテンシンｉｉ拮抗薬
JPH06312926A (ja)	1994-11-08	アンジオテンシンｉｉ拮抗薬
JP2564785B2 (ja)	1996-12-18	イミダゾピリジン誘導体及びその製法
AU8036998A (en)	1999-02-08	4,5-dihydro-{1h}-benz{g}indazole-3-carboxylic acid derivatives
JP2989865B2 (ja)	1999-12-13	ピロロキノリン誘導体、そのエステルおよびその塩
US5753672A (en)	1998-05-19	Imidazopyridine derivatives and process for preparing the same
JPH05202043A (ja)	1993-08-10	イミダゾール誘導体及びその製法
JPH06192258A (ja)	1994-07-12	新規１，６−ナフチリジン誘導体
JPH05201991A (ja)	1993-08-10	アミノ酸誘導体
JPH0753550A (ja)	1995-02-28	スルホニルベンジル−置換されたベンズイミダゾール類、それらの製造方法および薬品におけるそれらの使用
JPH072859A (ja)	1995-01-06	ピラゾール誘導体およびこれを有効成分とする医薬組成物
WO1993024487A1 (en)	1993-12-09	Nitrogen containing heterocyclic compounds as angiotensin-ii-antagonists