CS330591A3 - Imidazole and benzimidazole derivatives being substituted by indole and benzimidazole - Google Patents

Imidazole and benzimidazole derivatives being substituted by indole and benzimidazole Download PDF

Info

Publication number: CS330591A3
Authority: CS; Czechoslovakia
Prior art keywords: group; carbon atoms; compound; mmol; hydrogen
Prior art date: 1990-10-31

Application number

CS913305A

Other languages

Czech (cs)

English (en)

Inventor

Michael Anthony Poss

Original Assignee

Squibb & Sons Inc

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.)

1990-10-31

Filing date

1991-10-31

Publication date

1992-06-17

1991-10-31 Application filed by Squibb & Sons Inc filed Critical Squibb & Sons Inc

1992-06-17 Publication of CS330591A3 publication Critical patent/CS330591A3/cs

Links

PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims description 6
SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims description 5
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims description 4
125000001041 indolyl group Chemical group 0.000 title claims 2
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title description 12
150000001556 benzimidazoles Chemical class 0.000 title description 5
229940058303 antinematodal benzimidazole derivative Drugs 0.000 title description 4
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 title description 2
229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 272
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 127
-1 alkyl radicals Chemical class 0.000 claims description 107
239000000203 mixture Substances 0.000 claims description 90
125000004432 carbon atom Chemical group C* 0.000 claims description 69
125000000217 alkyl group Chemical group 0.000 claims description 46
239000001257 hydrogen Substances 0.000 claims description 39
229910052739 hydrogen Inorganic materials 0.000 claims description 39
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
150000003839 salts Chemical class 0.000 claims description 25
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 24
125000000753 cycloalkyl group Chemical group 0.000 claims description 21
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
125000001188 haloalkyl group Chemical group 0.000 claims description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
229910052799 carbon Inorganic materials 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 10
125000003710 aryl alkyl group Chemical group 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 8
239000005711 Benzoic acid Substances 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
239000000460 chlorine Substances 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
125000004494 ethyl ester group Chemical group 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
229940002612 prodrug Drugs 0.000 claims description 5
239000000651 prodrug Substances 0.000 claims description 5
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 4
206010020772 Hypertension Diseases 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
229910052717 sulfur Chemical group 0.000 claims description 4
239000011593 sulfur Chemical group 0.000 claims description 4
125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
WMHIWHPGXRRKJM-UHFFFAOYSA-N 1-phenylindole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC=CC=C2N1C1=CC=CC=C1 WMHIWHPGXRRKJM-UHFFFAOYSA-N 0.000 claims description 2
206010019280 Heart failures Diseases 0.000 claims description 2
125000002252 acyl group Chemical group 0.000 claims description 2
125000001931 aliphatic group Chemical group 0.000 claims description 2
229940030600 antihypertensive agent Drugs 0.000 claims description 2
239000002220 antihypertensive agent Substances 0.000 claims description 2
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 2
125000005357 cycloalkylalkynyl group Chemical group 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
150000003254 radicals Chemical class 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 3
150000001721 carbon Chemical group 0.000 claims 2
125000001309 chloro group Chemical group Cl* 0.000 claims 2
125000002883 imidazolyl group Chemical group 0.000 claims 2
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims 1
101100440696 Caenorhabditis elegans cor-1 gene Proteins 0.000 claims 1
UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 claims 1
230000000747 cardiac effect Effects 0.000 claims 1
239000003814 drug Substances 0.000 claims 1
229940079593 drug Drugs 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
239000002184 metal Substances 0.000 claims 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims 1
230000002265 prevention Effects 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 228
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 185
239000011541 reaction mixture Substances 0.000 description 183
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 156
239000000243 solution Substances 0.000 description 133
238000002360 preparation method Methods 0.000 description 121
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 111
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 92
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 83
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 81
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
239000000741 silica gel Substances 0.000 description 77
229910002027 silica gel Inorganic materials 0.000 description 77
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 74
238000000034 method Methods 0.000 description 64
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 63
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
239000000047 product Substances 0.000 description 50
239000007787 solid Substances 0.000 description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
238000004809 thin layer chromatography Methods 0.000 description 29
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 27
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 27
239000000284 extract Substances 0.000 description 26
239000002904 solvent Substances 0.000 description 26
229940126062 Compound A Drugs 0.000 description 25
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 25
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 24
229910052943 magnesium sulfate Inorganic materials 0.000 description 22
235000019341 magnesium sulphate Nutrition 0.000 description 22
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
239000003480 eluent Substances 0.000 description 21
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 20
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 20
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
239000011347 resin Substances 0.000 description 18
229920005989 resin Polymers 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 17
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Inorganic materials [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 17
229910052938 sodium sulfate Inorganic materials 0.000 description 16
235000011152 sodium sulphate Nutrition 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000002253 acid Substances 0.000 description 15
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 14
229960001701 chloroform Drugs 0.000 description 14
239000008096 xylene Substances 0.000 description 14
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 13
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
IJIBRSFAXRFPPN-UHFFFAOYSA-N 5-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C=C1C=O IJIBRSFAXRFPPN-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 12
238000010828 elution Methods 0.000 description 12
150000002431 hydrogen Chemical group 0.000 description 12
229920006395 saturated elastomer Polymers 0.000 description 12
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
229910000024 caesium carbonate Inorganic materials 0.000 description 11
239000000706 filtrate Substances 0.000 description 11
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 10
239000000463 material Substances 0.000 description 10
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 9
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 9
238000003818 flash chromatography Methods 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
235000015497 potassium bicarbonate Nutrition 0.000 description 9
229910000028 potassium bicarbonate Inorganic materials 0.000 description 9
239000011736 potassium bicarbonate Substances 0.000 description 9
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 9
150000003738 xylenes Chemical class 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
239000012267 brine Substances 0.000 description 8
229910052731 fluorine Inorganic materials 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
230000008018 melting Effects 0.000 description 8
238000002844 melting Methods 0.000 description 8
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
239000012279 sodium borohydride Substances 0.000 description 8
229910000033 sodium borohydride Inorganic materials 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 8
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
239000000908 ammonium hydroxide Substances 0.000 description 7
239000012298 atmosphere Substances 0.000 description 7
239000000872 buffer Substances 0.000 description 7
238000010898 silica gel chromatography Methods 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 6
150000001299 aldehydes Chemical class 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
239000007853 buffer solution Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
238000001816 cooling Methods 0.000 description 6
239000011737 fluorine Substances 0.000 description 6
239000010410 layer Substances 0.000 description 6
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
239000012528 membrane Substances 0.000 description 6
229920000515 polycarbonate Polymers 0.000 description 6
239000004417 polycarbonate Substances 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 5
102000005862 Angiotensin II Human genes 0.000 description 5
101800000733 Angiotensin-2 Proteins 0.000 description 5
QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 5
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 5
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
229950006323 angiotensin ii Drugs 0.000 description 5
QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 5
239000012043 crude product Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 5
239000001632 sodium acetate Substances 0.000 description 5
235000017281 sodium acetate Nutrition 0.000 description 5
235000009518 sodium iodide Nutrition 0.000 description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
235000010233 benzoic acid Nutrition 0.000 description 4
239000002934 diuretic Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
235000011181 potassium carbonates Nutrition 0.000 description 4
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
239000004627 regenerated cellulose Substances 0.000 description 4
238000004366 reverse phase liquid chromatography Methods 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
239000007858 starting material Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
235000005074 zinc chloride Nutrition 0.000 description 4
239000011592 zinc chloride Substances 0.000 description 4
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 3
JLVIHQCWASNXCK-UHFFFAOYSA-N 2-butyl-5-chloro-1h-imidazole-4-carbaldehyde Chemical compound CCCCC1=NC(C=O)=C(Cl)N1 JLVIHQCWASNXCK-UHFFFAOYSA-N 0.000 description 3
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XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
238000007259 addition reaction Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
230000001668 ameliorated effect Effects 0.000 description 1
XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
229960002576 amiloride Drugs 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
229960003515 bendroflumethiazide Drugs 0.000 description 1
HDWIHXWEUNVBIY-UHFFFAOYSA-N bendroflumethiazidum Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1=CC=CC=C1 HDWIHXWEUNVBIY-UHFFFAOYSA-N 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
229960001541 benzthiazide Drugs 0.000 description 1
NDTSRXAMMQDVSW-UHFFFAOYSA-N benzthiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1N=C2CSCC1=CC=CC=C1 NDTSRXAMMQDVSW-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 1
229960004064 bumetanide Drugs 0.000 description 1
KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
HJUGFYREWKUQJT-UHFFFAOYSA-N carbon tetrabromide Natural products BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
150000001804 chlorine Chemical class 0.000 description 1
229910001919 chlorite Inorganic materials 0.000 description 1
229910052619 chlorite group Inorganic materials 0.000 description 1
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
229940106681 chloroacetic acid Drugs 0.000 description 1
229960002155 chlorothiazide Drugs 0.000 description 1
QBWCMBCROVPCKQ-UHFFFAOYSA-N chlorous acid Chemical compound OCl=O QBWCMBCROVPCKQ-UHFFFAOYSA-N 0.000 description 1
229960001523 chlortalidone Drugs 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical class OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
QXCKBQXFEWQNAE-UHFFFAOYSA-N ethyl 1-(2-cyanophenyl)-5-methylindole-2-carboxylate Chemical compound CCOC(=O)C1=CC2=CC(C)=CC=C2N1C1=CC=CC=C1C#N QXCKBQXFEWQNAE-UHFFFAOYSA-N 0.000 description 1
YZMNPRGMGVPACV-UHFFFAOYSA-N ethyl 2-(4-methylindol-1-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC=C1N1C2=CC=CC(C)=C2C=C1 YZMNPRGMGVPACV-UHFFFAOYSA-N 0.000 description 1
BIHHBTVQFPVSTE-UHFFFAOYSA-N ethyl 2-bromobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1Br BIHHBTVQFPVSTE-UHFFFAOYSA-N 0.000 description 1
ZQBIGESTMJGOAX-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-2-hydroxyimino-3-oxobutanoate Chemical compound CCOC(=O)C(=NO)C(=O)C(F)(F)F ZQBIGESTMJGOAX-UHFFFAOYSA-N 0.000 description 1
ITEZOSNBYWFOAO-UHFFFAOYSA-N ethyl 5-(bromomethyl)-1-(2-cyanophenyl)indole-2-carboxylate Chemical compound C(C)OC(=O)C=1N(C2=CC=C(C=C2C1)CBr)C1=C(C=CC=C1)C#N ITEZOSNBYWFOAO-UHFFFAOYSA-N 0.000 description 1
WPKZIWRUDDVDQI-UHFFFAOYSA-N ethyl 5-(bromomethyl)-1-phenylindole-2-carboxylate Chemical compound CCOC(=O)C1=CC2=CC(CBr)=CC=C2N1C1=CC=CC=C1 WPKZIWRUDDVDQI-UHFFFAOYSA-N 0.000 description 1
KMVFKXFOPNKHEM-UHFFFAOYSA-N ethyl 5-methyl-1h-indole-2-carboxylate Chemical compound CC1=CC=C2NC(C(=O)OCC)=CC2=C1 KMVFKXFOPNKHEM-UHFFFAOYSA-N 0.000 description 1
229940117360 ethyl pyruvate Drugs 0.000 description 1
229960003028 flumethiazide Drugs 0.000 description 1
RGUQWGXAYZNLMI-UHFFFAOYSA-N flumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O RGUQWGXAYZNLMI-UHFFFAOYSA-N 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
229960003883 furosemide Drugs 0.000 description 1
239000005337 ground glass Substances 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
229960002003 hydrochlorothiazide Drugs 0.000 description 1
229960003313 hydroflumethiazide Drugs 0.000 description 1
DMDGGSIALPNSEE-UHFFFAOYSA-N hydroflumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O DMDGGSIALPNSEE-UHFFFAOYSA-N 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
RBLWMQWAHONKNC-UHFFFAOYSA-N hydroxyazanium Chemical compound O[NH3+] RBLWMQWAHONKNC-UHFFFAOYSA-N 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000003999 initiator Substances 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000003993 interaction Effects 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
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
DVLGIQNHKLWSRU-UHFFFAOYSA-N methyl 1h-imidazole-5-carboxylate Chemical compound COC(=O)C1=CN=CN1 DVLGIQNHKLWSRU-UHFFFAOYSA-N 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
YTXAYGAYACWVGD-UHFFFAOYSA-N palladium;hydrate Chemical compound O.[Pd] YTXAYGAYACWVGD-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000003884 phenylalkyl group Chemical group 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
229960005483 polythiazide Drugs 0.000 description 1
229920000046 polythiazide Polymers 0.000 description 1
CBPYOHALYYGNOE-UHFFFAOYSA-M potassium;3,5-dinitrobenzoate Chemical compound [K+].[O-]C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 CBPYOHALYYGNOE-UHFFFAOYSA-M 0.000 description 1
BEBPTRYPELOERP-UHFFFAOYSA-M potassium;methanethiolate Chemical class [K+].[S-]C BEBPTRYPELOERP-UHFFFAOYSA-M 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
PZQSQRCNMZGWFT-QXMHVHEDSA-N propan-2-yl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC(C)C PZQSQRCNMZGWFT-QXMHVHEDSA-N 0.000 description 1
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
229960002256 spironolactone Drugs 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000000725 suspension Substances 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Substances [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
150000004685 tetrahydrates Chemical class 0.000 description 1
239000003451 thiazide diuretic agent Substances 0.000 description 1
AGHANLSBXUWXTB-UHFFFAOYSA-N tienilic acid Chemical compound ClC1=C(Cl)C(OCC(=O)O)=CC=C1C(=O)C1=CC=CS1 AGHANLSBXUWXTB-UHFFFAOYSA-N 0.000 description 1
229960000356 tienilic acid Drugs 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 1
229960001288 triamterene Drugs 0.000 description 1
MCXWSZYODJGJIB-UHFFFAOYSA-N triazido(butyl)stannane Chemical compound CCCC[Sn](N=[N+]=[N-])(N=[N+]=[N-])N=[N+]=[N-] MCXWSZYODJGJIB-UHFFFAOYSA-N 0.000 description 1
PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
229960004813 trichlormethiazide Drugs 0.000 description 1
LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- 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
- 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
- A61P9/08—Vasodilators for multiple indications
- 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
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- 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
- C07D403/06—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 only aliphatic carbon atoms
- 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
- C07D403/14—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 three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Cardiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CS913305A 1990-10-31 1991-10-31 Imidazole and benzimidazole derivatives being substituted by indole and benzimidazole CS330591A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US60663190A	1990-10-31	1990-10-31

Publications (1)

Publication Number	Publication Date
CS330591A3 true CS330591A3 (en)	1992-06-17

Family

ID=24428787

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS913305A CS330591A3 (en)	1990-10-31	1991-10-31	Imidazole and benzimidazole derivatives being substituted by indole and benzimidazole

Country Status (23)

Country	Link
EP (1)	EP0488532A1 (ja)
JP (1)	JPH0592969A (ja)
KR (1)	KR920008032A (ja)
CN (1)	CN1061224A (ja)
AU (1)	AU650294B2 (ja)
CA (1)	CA2054594A1 (ja)
CS (1)	CS330591A3 (ja)
EG (1)	EG19826A (ja)
FI (1)	FI915148A7 (ja)
HU (1)	HU214575B (ja)
IE (1)	IE913785A1 (ja)
IL (1)	IL99917A0 (ja)
MX (1)	MX9101873A (ja)
MY (1)	MY108611A (ja)
NO (1)	NO180749C (ja)
NZ (1)	NZ240383A (ja)
PH (1)	PH31175A (ja)
PL (1)	PL168902B1 (ja)
PT (1)	PT99404A (ja)
RO (1)	RO109735B1 (ja)
RU (1)	RU2111208C1 (ja)
YU (1)	YU173791A (ja)
ZA (1)	ZA918688B (ja)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PT95899A (pt) *	1989-11-17	1991-09-13	Glaxo Group Ltd	Processo para a preparacao de derivados indole
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1991
- 1991-10-23 PH PH43330A patent/PH31175A/en unknown
- 1991-10-29 NZ NZ240383A patent/NZ240383A/en unknown
- 1991-10-30 IE IE378591A patent/IE913785A1/en not_active Application Discontinuation
- 1991-10-30 HU HU913418A patent/HU214575B/hu not_active IP Right Cessation
- 1991-10-30 RU SU5010095A patent/RU2111208C1/ru active
- 1991-10-30 NO NO914263A patent/NO180749C/no unknown
- 1991-10-30 EG EG66391A patent/EG19826A/xx active
- 1991-10-30 RO RO148651A patent/RO109735B1/ro unknown
- 1991-10-31 IL IL99917A patent/IL99917A0/xx unknown
- 1991-10-31 EP EP91310076A patent/EP0488532A1/en not_active Ceased
- 1991-10-31 MY MYPI9102106 patent/MY108611A/xx unknown
- 1991-10-31 KR KR1019910019254A patent/KR920008032A/ko not_active Abandoned
- 1991-10-31 YU YU173791A patent/YU173791A/sh unknown
- 1991-10-31 PT PT99404A patent/PT99404A/pt not_active Application Discontinuation
- 1991-10-31 AU AU86910/91A patent/AU650294B2/en not_active Ceased
- 1991-10-31 JP JP3286584A patent/JPH0592969A/ja active Pending
- 1991-10-31 MX MX9101873A patent/MX9101873A/es not_active IP Right Cessation
- 1991-10-31 PL PL91292249A patent/PL168902B1/pl unknown
- 1991-10-31 CN CN91110565A patent/CN1061224A/zh active Pending
- 1991-10-31 ZA ZA918688A patent/ZA918688B/xx unknown
- 1991-10-31 CA CA002054594A patent/CA2054594A1/en not_active Abandoned
- 1991-10-31 CS CS913305A patent/CS330591A3/cs unknown
- 1991-10-31 FI FI915148A patent/FI915148A7/fi unknown

Also Published As

Publication number	Publication date
NO180749B (no)	1997-03-03
IL99917A0 (en)	1992-08-18
HUT59677A (en)	1992-06-29
MX9101873A (es)	1992-06-05
FI915148A0 (fi)	1991-10-31
PL168902B1 (pl)	1996-05-31
HU214575B (hu)	1998-04-28
JPH0592969A (ja)	1993-04-16
NO180749C (no)	1997-06-11
RU2111208C1 (ru)	1998-05-20
PH31175A (en)	1998-03-20
EG19826A (en)	1996-03-31
NZ240383A (en)	1994-12-22
YU173791A (sh)	1994-01-20
PT99404A (pt)	1992-09-30
NO914263D0 (no)	1991-10-30
HU913418D0 (en)	1992-01-28
FI915148A7 (fi)	1992-05-01
KR920008032A (ko)	1992-05-27
RO109735B1 (ro)	1995-05-30
NO914263L (no)	1992-05-04
CN1061224A (zh)	1992-05-20
IE913785A1 (en)	1992-05-22
EP0488532A1 (en)	1992-06-03
AU650294B2 (en)	1994-06-16
PL292249A1 (en)	1992-07-13
CA2054594A1 (en)	1992-05-01
MY108611A (en)	1996-10-31
ZA918688B (en)	1992-08-26
AU8691091A (en)	1992-05-07

Publication	Publication Date	Title
US5374615A (en)	1994-12-20	Indole- and benzimidazole-substituted imidazole and benzimidazole derivatives
AU650294B2 (en)	1994-06-16	Indole-and benzimidazole-substituted imidazole and benzimidazole derivatives
EP0450566B1 (de)	1995-07-05	Substituierte Azole, Verfahren zu deren Herstellung, diese enthaltende Mittel und deren Verwendung
US5190942A (en)	1993-03-02	Benzoxazole and related heterocyclic substituted imidazole and benzimidazole derivatives
US5436260A (en)	1995-07-25	Angiotensin II receptor antagonists
US5322950A (en)	1994-06-21	Imidazole with angiotensin II antagonist properties
US5378704A (en)	1995-01-03	Non-peptidic angiotensin-II-receptor-antagonists
NZ525917A (en)	2005-11-25	Phenylethenyl or phenylethinyl derivatives as glutamate receptor antagonists and their use in treating mGLuR5 receptor mediated disorders
US5208235A (en)	1993-05-04	Indole- and benzimidazole-substituted imidazole derivatives
US5212177A (en)	1993-05-18	Indole and benzimidazole-substituted dihydropyrimidine derivatives
WO1992004343A1 (fr)	1992-03-19	Nouveau derive de tetrahydrobenzazole
FI110512B (fi)	2003-02-14	Menetelmä angiotensiini II:n antagonisteina käyttökelpoisten substituoitujen indolien valmistamiseksi
SK2895A3 (en)	1995-07-11	Substituted 3-cyclobutene-1,2-diones, method of their preparation and pharmaceutical agents which containing thereof
EP0485929A1 (de)	1992-05-20	Substituierte Azole, Verfahren zu ihrer Herstellung und ihre Verwendung
SK297692A3 (en)	1995-09-13	Imidazolylpropene acid substituted derivatives
HU217627B (hu)	2000-03-28	Eljárás bifenil-szubsztituált kinolin- és naftiridinszármazékok és ezeket tartalmazó gyógyszerkészítmények előállítására
DE4142366A1 (de)	1993-06-24	Phenylalkylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
US5389661A (en)	1995-02-14	Imidazole and 1,2,4-triazole derivatives with angiotensin II antagonist properties
CA2061159A1 (en)	1992-08-27	Imidazole and benzimidazole derivatives
CA2085310A1 (en)	1993-06-17	Substituted indole and benzimidazole derivatives
PT99008A (pt)	1992-07-31	Processo para a preparacao de compostos 1,3,5-trisubstituido-1,2,4-triazole para o tratamento de perturbacoes circulatorias
HU206343B (en)	1992-10-28	Process for producing 1,2-benzizoxazol- and 1,2-benzizothiazol derivatives and pharmaceutical compositions containing them
US5466704A (en)	1995-11-14	N-substituted imidazole and benzimidazole derivatives useful as angiotenson II antagonists
MC1962A1 (fr)	1989-06-30	Derives du benzimidazole
HK1002004A (en)	1998-07-24	Indole- and benzimidazole-substituted imidazole and benzimidazole derivatives