CA2054465A1 - Derives du thienoimidazole, leurs production et leur utilisation - Google Patents

Derives du thienoimidazole, leurs production et leur utilisation

Info

Publication number: CA2054465A1
Authority: CA; Canada
Prior art keywords: group; alkyl; methyl; optionally substituted; alkoxy
Prior art date: 1990-10-29
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA 2054465

Other languages

English (en)

Inventor

Takehiko Naka

Yoshiyuki Inada

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

Takeda Pharmaceutical Co Ltd

Original Assignee

Individual

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

1990-10-29

Filing date

1991-10-29

Publication date

1992-05-01

1990-10-29 Priority claimed from JP2291043A external-priority patent/JPH04167678A/ja

1991-10-29 Application filed by Individual filed Critical Individual

1992-05-01 Publication of CA2054465A1 publication Critical patent/CA2054465A1/fr

Status Abandoned legal-status Critical Current

Links

238000004519 manufacturing process Methods 0.000 title claims description 5
JCZAVVUIFWZMQI-UHFFFAOYSA-N 1h-thieno[2,3-d]imidazole Chemical class N1C=NC2=C1C=CS2 JCZAVVUIFWZMQI-UHFFFAOYSA-N 0.000 title description 3
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
239000001257 hydrogen Substances 0.000 claims abstract description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
150000003839 salts Chemical class 0.000 claims abstract description 21
229950006323 angiotensin ii Drugs 0.000 claims abstract description 18
102000005862 Angiotensin II Human genes 0.000 claims abstract description 17
101800000733 Angiotensin-2 Proteins 0.000 claims abstract description 17
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 claims abstract description 17
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
125000005842 heteroatom Chemical group 0.000 claims abstract description 14
150000001450 anions Chemical class 0.000 claims abstract description 11
239000003814 drug Substances 0.000 claims abstract description 9
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 8
230000003042 antagnostic effect Effects 0.000 claims abstract description 8
125000006850 spacer group Chemical group 0.000 claims abstract description 8
238000006467 substitution reaction Methods 0.000 claims abstract description 7
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 6
125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 6
150000001875 compounds Chemical class 0.000 claims description 195
-1 nitro, cyano, amino Chemical group 0.000 claims description 112
125000000217 alkyl group Chemical group 0.000 claims description 54
229910052736 halogen Inorganic materials 0.000 claims description 30
150000002367 halogens Chemical group 0.000 claims description 30
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims description 26
125000003545 alkoxy group Chemical group 0.000 claims description 22
125000003831 tetrazolyl group Chemical group 0.000 claims description 22
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
125000004432 carbon atom Chemical group C* 0.000 claims description 20
239000000460 chlorine Substances 0.000 claims description 20
125000003282 alkyl amino group Chemical group 0.000 claims description 18
125000003342 alkenyl group Chemical group 0.000 claims description 16
125000000753 cycloalkyl group Chemical group 0.000 claims description 14
125000002252 acyl group Chemical group 0.000 claims description 13
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
125000003302 alkenyloxy group Chemical group 0.000 claims description 9
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
239000000126 substance Substances 0.000 claims description 8
125000000304 alkynyl group Chemical group 0.000 claims description 7
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
125000001589 carboacyl group Chemical group 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
125000004414 alkyl thio group Chemical group 0.000 claims description 5
125000003710 aryl alkyl group Chemical group 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
125000005415 substituted alkoxy group Chemical group 0.000 claims description 5
125000000542 sulfonic acid group Chemical group 0.000 claims description 5
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 claims description 5
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
230000004962 physiological condition Effects 0.000 claims description 3
ZOEDEYCGZMEXRS-UHFFFAOYSA-N 2-ethylsulfanyl-6-methyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylic acid Chemical compound CCSC1=NC2=C(C)SC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 ZOEDEYCGZMEXRS-UHFFFAOYSA-N 0.000 claims description 2
RQFUSHUISPDVCQ-UHFFFAOYSA-N 2-methoxy-6-methyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylic acid Chemical compound COC1=NC2=C(C)SC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 RQFUSHUISPDVCQ-UHFFFAOYSA-N 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 22
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 18
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 7
125000003107 substituted aryl group Chemical group 0.000 claims 5
238000009740 moulding (composite fabrication) Methods 0.000 claims 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
125000000041 C6-C10 aryl group Chemical group 0.000 claims 3
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims 3
KAKQVSNHTBLJCH-UHFFFAOYSA-N trifluoromethanesulfonimidic acid Chemical compound NS(=O)(=O)C(F)(F)F KAKQVSNHTBLJCH-UHFFFAOYSA-N 0.000 claims 3
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 2
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 2
229910000147 aluminium phosphate Inorganic materials 0.000 claims 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
KKPGXJNZFUKWLX-UHFFFAOYSA-N (trifluoromethylsulfonylamino) dihydrogen phosphate Chemical group FC(S(=O)(=O)NOP(O)(O)=O)(F)F KKPGXJNZFUKWLX-UHFFFAOYSA-N 0.000 claims 1
BFDOZXJMEKENFI-UHFFFAOYSA-N 2-ethoxy-6-methyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylic acid Chemical compound CCOC1=NC2=C(C)SC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 BFDOZXJMEKENFI-UHFFFAOYSA-N 0.000 claims 1
LGJJRWCUDWXHDJ-UHFFFAOYSA-N 6-methyl-2-propoxy-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylic acid Chemical compound CCCOC1=NC2=C(C)SC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 LGJJRWCUDWXHDJ-UHFFFAOYSA-N 0.000 claims 1
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 1
PMNMOFKWWPEXHV-UHFFFAOYSA-N acetyloxymethyl 2-methoxy-6-methyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylate Chemical compound COC1=NC2=C(C)SC(C(=O)OCOC(C)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 PMNMOFKWWPEXHV-UHFFFAOYSA-N 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
125000000547 substituted alkyl group Chemical group 0.000 claims 1
206010020772 Hypertension Diseases 0.000 abstract description 6
208000006011 Stroke Diseases 0.000 abstract description 6
230000003389 potentiating effect Effects 0.000 abstract description 6
206010008190 Cerebrovascular accident Diseases 0.000 abstract description 5
206010019280 Heart failures Diseases 0.000 abstract description 5
230000002490 cerebral effect Effects 0.000 abstract description 5
201000010099 disease Diseases 0.000 abstract description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
206010061216 Infarction Diseases 0.000 abstract description 4
230000000747 cardiac effect Effects 0.000 abstract description 4
208000019622 heart disease Diseases 0.000 abstract description 4
230000007574 infarction Effects 0.000 abstract description 4
201000008383 nephritis Diseases 0.000 abstract description 4
230000003276 anti-hypertensive effect Effects 0.000 abstract description 3
229940124597 therapeutic agent Drugs 0.000 abstract description 3
229940058303 antinematodal benzimidazole derivative Drugs 0.000 abstract description 2
125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 abstract description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 105
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 84
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 80
238000000921 elemental analysis Methods 0.000 description 70
239000000203 mixture Substances 0.000 description 67
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
229910001868 water Inorganic materials 0.000 description 64
238000006243 chemical reaction Methods 0.000 description 63
239000013078 crystal Substances 0.000 description 63
238000005160 1H NMR spectroscopy Methods 0.000 description 62
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
238000000034 method Methods 0.000 description 54
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 51
238000005481 NMR spectroscopy Methods 0.000 description 49
239000000243 solution Substances 0.000 description 46
239000011541 reaction mixture Substances 0.000 description 45
101150041968 CDC13 gene Proteins 0.000 description 41
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 41
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
239000002904 solvent Substances 0.000 description 37
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
238000001953 recrystallisation Methods 0.000 description 30
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
238000010992 reflux Methods 0.000 description 21
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 17
238000010898 silica gel chromatography Methods 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
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 14
239000002168 alkylating agent Substances 0.000 description 13
229940100198 alkylating agent Drugs 0.000 description 13
239000002585 base Substances 0.000 description 13
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
229910000041 hydrogen chloride Inorganic materials 0.000 description 13
235000011121 sodium hydroxide Nutrition 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
238000004440 column chromatography Methods 0.000 description 12
235000008504 concentrate Nutrition 0.000 description 12
239000012141 concentrate Substances 0.000 description 12
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 11
238000000605 extraction Methods 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
229910000027 potassium carbonate Inorganic materials 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
239000012312 sodium hydride Substances 0.000 description 8
229910000104 sodium hydride Inorganic materials 0.000 description 8
230000009471 action Effects 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
239000002775 capsule Substances 0.000 description 7
150000007942 carboxylates Chemical class 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
238000001816 cooling Methods 0.000 description 7
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 7
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
239000008187 granular material Substances 0.000 description 7
150000002430 hydrocarbons Chemical group 0.000 description 7
239000000047 product Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
239000003826 tablet Substances 0.000 description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
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 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
229920002678 cellulose Polymers 0.000 description 6
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 6
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
239000008101 lactose Substances 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
235000011181 potassium carbonates Nutrition 0.000 description 6
102000005962 receptors Human genes 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
239000006188 syrup Substances 0.000 description 6
235000020357 syrup Nutrition 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 5
239000001913 cellulose Substances 0.000 description 5
229910052731 fluorine Inorganic materials 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 5
239000007800 oxidant agent Substances 0.000 description 5
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
229940123413 Angiotensin II antagonist Drugs 0.000 description 4
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
239000003708 ampul Substances 0.000 description 4
239000002333 angiotensin II receptor antagonist Substances 0.000 description 4
OSJRGDBEYARHLX-UHFFFAOYSA-N azido(trimethyl)stannane Chemical compound [N-]=[N+]=[N-].C[Sn+](C)C OSJRGDBEYARHLX-UHFFFAOYSA-N 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
238000009835 boiling Methods 0.000 description 4
229940079593 drug Drugs 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
150000004702 methyl esters Chemical class 0.000 description 4
239000012434 nucleophilic reagent Substances 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
238000011160 research Methods 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
235000017550 sodium carbonate Nutrition 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
102000008873 Angiotensin II receptor Human genes 0.000 description 3
108050000824 Angiotensin II receptor Proteins 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
150000001540 azides Chemical class 0.000 description 3
239000004305 biphenyl Substances 0.000 description 3
235000010290 biphenyl Nutrition 0.000 description 3
238000000748 compression moulding Methods 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
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238000010511 deprotection reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
CCAFPWNGIUBUSD-UHFFFAOYSA-N diethyl sulfoxide Chemical compound CCS(=O)CC CCAFPWNGIUBUSD-UHFFFAOYSA-N 0.000 description 1
MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000003792 electrolyte Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
BDHXJIRTSWHBPR-UHFFFAOYSA-N ethyl 1-iodoethyl carbonate Chemical compound CCOC(=O)OC(C)I BDHXJIRTSWHBPR-UHFFFAOYSA-N 0.000 description 1
ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
WDCDAAMJNUHOIY-UHFFFAOYSA-N ethyl acetate;2-propan-2-yloxypropane Chemical compound CCOC(C)=O.CC(C)OC(C)C WDCDAAMJNUHOIY-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
KCOPWUJJPSTRIZ-UHFFFAOYSA-N ethyl ethanedithioate Chemical compound CCSC(C)=S KCOPWUJJPSTRIZ-UHFFFAOYSA-N 0.000 description 1
XLVSXTNEASHWQT-UHFFFAOYSA-N ethyl pentanimidate;hydrochloride Chemical compound Cl.CCCCC(=N)OCC XLVSXTNEASHWQT-UHFFFAOYSA-N 0.000 description 1
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
210000001105 femoral artery Anatomy 0.000 description 1
210000003191 femoral vein Anatomy 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012025 fluorinating agent Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
MOTRZVVGCFFABN-UHFFFAOYSA-N hexane;2-propan-2-yloxypropane Chemical compound CCCCCC.CC(C)OC(C)C MOTRZVVGCFFABN-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000003284 homeostatic effect Effects 0.000 description 1
FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
150000004694 iodide salts Chemical class 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
239000010410 layer Substances 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
238000005259 measurement Methods 0.000 description 1
QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
XZNOPNMOCOMOGB-UHFFFAOYSA-N methyl 2-hexylsulfanyl-4-methyl-1h-thieno[3,4-d]imidazole-6-carboxylate Chemical compound S1C(C(=O)OC)=C2NC(SCCCCCC)=NC2=C1C XZNOPNMOCOMOGB-UHFFFAOYSA-N 0.000 description 1
RILYADQKLMZBIO-UHFFFAOYSA-N methyl 2-sulfanylidene-1,3-dihydrothieno[3,4-d]imidazole-4-carboxylate Chemical compound N1C(S)=NC2=C(C(=O)OC)SC=C21 RILYADQKLMZBIO-UHFFFAOYSA-N 0.000 description 1
PZHNENDGTWNESN-UHFFFAOYSA-N methyl 3,4-diaminothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=C(N)C=1N PZHNENDGTWNESN-UHFFFAOYSA-N 0.000 description 1
PPKZBDPFGYPNAA-UHFFFAOYSA-N methyl 3-(butanoylamino)-4-cyano-5-methylthiophene-2-carboxylate Chemical compound CCCC(=O)NC1=C(C(=O)OC)SC(C)=C1C#N PPKZBDPFGYPNAA-UHFFFAOYSA-N 0.000 description 1
QVDKSCBMAPUYEJ-UHFFFAOYSA-N methyl 4-methyl-1h-thieno[3,4-d]imidazole-6-carboxylate Chemical compound N1=CNC2=C(C(=O)OC)SC(C)=C21 QVDKSCBMAPUYEJ-UHFFFAOYSA-N 0.000 description 1
YACSXAVOHTZSSI-UHFFFAOYSA-N methyl 4-methyl-2-propan-2-ylsulfanyl-1h-thieno[3,4-d]imidazole-6-carboxylate Chemical compound N1=C(SC(C)C)NC2=C(C(=O)OC)SC(C)=C21 YACSXAVOHTZSSI-UHFFFAOYSA-N 0.000 description 1
PEMLQUOEANWDDA-UHFFFAOYSA-N methyl 4-methyl-2-propylsulfanyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-6-carboxylate Chemical compound CCCSC1=NC2=C(C(=O)OC)SC(C)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 PEMLQUOEANWDDA-UHFFFAOYSA-N 0.000 description 1
VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
OCMKTKVINZXSSC-UHFFFAOYSA-N methyl 6-methyl-2-methylsulfanyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylate Chemical compound C12=C(C(=O)OC)SC(C)=C2N=C(SC)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 OCMKTKVINZXSSC-UHFFFAOYSA-N 0.000 description 1
HSDMJKOFZMHHFC-UHFFFAOYSA-N methyl 6-methyl-2-propan-2-yl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylate Chemical compound C12=C(C(=O)OC)SC(C)=C2N=C(C(C)C)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 HSDMJKOFZMHHFC-UHFFFAOYSA-N 0.000 description 1
SUYTUJBUGOTNIS-UHFFFAOYSA-N methyl 6-methyl-2-sulfanylidene-1,3-dihydrothieno[3,4-d]imidazole-4-carboxylate Chemical compound N1C(=S)NC2=C(C(=O)OC)SC(C)=C21 SUYTUJBUGOTNIS-UHFFFAOYSA-N 0.000 description 1
GAGZNJGQPOZFLH-UHFFFAOYSA-N methyl 6-methyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylate Chemical compound C12=C(C(=O)OC)SC(C)=C2N=CN1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 GAGZNJGQPOZFLH-UHFFFAOYSA-N 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
VXFSTFCBJBTCMM-UHFFFAOYSA-N o-methyl 2,4-dimethyl-1h-thieno[3,4-d]imidazole-6-carbothioate Chemical compound N1=C(C)NC2=C(C(=S)OC)SC(C)=C21 VXFSTFCBJBTCMM-UHFFFAOYSA-N 0.000 description 1
KDZHRPZBMZJSGR-UHFFFAOYSA-N o-methyl 2-ethyl-1h-thieno[3,4-d]imidazole-4-carbothioate Chemical compound S1C=C2NC(CC)=NC2=C1C(=S)OC KDZHRPZBMZJSGR-UHFFFAOYSA-N 0.000 description 1
XEOHVNOSZMADIO-UHFFFAOYSA-N o-methyl 3,4-diamino-5-methylthiophene-2-carbothioate Chemical compound COC(=S)C=1SC(C)=C(N)C=1N XEOHVNOSZMADIO-UHFFFAOYSA-N 0.000 description 1
RQCNLKUFGZEUKU-UHFFFAOYSA-N o-methyl 4-methyl-2-propyl-1h-thieno[3,4-d]imidazole-6-carbothioate Chemical compound S1C(C(=S)OC)=C2NC(CCC)=NC2=C1C RQCNLKUFGZEUKU-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000004967 organic peroxy acids Chemical class 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen 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
229960001412 pentobarbital Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
HANHXLJTDBNSPS-UHFFFAOYSA-N phenyl 1H-thieno[3,4-d]imidazole-4-carboxylate Chemical compound C1(=CC=CC=C1)OC(=O)C=1SC=C2C1N=CN2 HANHXLJTDBNSPS-UHFFFAOYSA-N 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000000651 prodrug Chemical class 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
PFGWGEPQIUAZME-NXSMLHPHSA-N saralasin Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)C1=CC=C(O)C=C1 PFGWGEPQIUAZME-NXSMLHPHSA-N 0.000 description 1
229960004785 saralasin Drugs 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
KTORSEUXHRSIBX-UHFFFAOYSA-M sodium;2-ethylsulfanyl-6-methyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylate Chemical compound [Na+].CCSC1=NC2=C(C)SC(C([O-])=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 KTORSEUXHRSIBX-UHFFFAOYSA-M 0.000 description 1
YNAOWSHNOYAIKX-UHFFFAOYSA-M sodium;2-methoxy-6-methyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]thieno[3,4-d]imidazole-4-carboxylate Chemical compound [Na+].COC1=NC2=C(C)SC(C([O-])=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 YNAOWSHNOYAIKX-UHFFFAOYSA-M 0.000 description 1
GYBMSOFSBPZKCX-UHFFFAOYSA-N sodium;ethanol;ethanolate Chemical compound [Na+].CCO.CC[O-] GYBMSOFSBPZKCX-UHFFFAOYSA-N 0.000 description 1
239000008279 sol Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
AGZYNVVJQAOVRP-UHFFFAOYSA-N thiophene-3,4-diamine Chemical compound NC1=CSC=C1N AGZYNVVJQAOVRP-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
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
LYRCQNDYYRPFMF-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C LYRCQNDYYRPFMF-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
239000005526 vasoconstrictor agent Substances 0.000 description 1
UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA 2054465 1990-10-29 1991-10-29 Derives du thienoimidazole, leurs production et leur utilisation Abandoned CA2054465A1 (fr)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
JP2291043A JPH04167678A (ja)	1990-10-29	1990-10-29	ゴースト除去装置
JP294655-1990		1990-10-30
JP092081-1991		1991-04-23
JP9208191		1991-04-23
JP150643-1991		1991-06-21
JP15064391		1991-06-21

Publications (1)

Publication Number	Publication Date
CA2054465A1 true CA2054465A1 (fr)	1992-05-01

Family

ID=27306933

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2054465 Abandoned CA2054465A1 (fr)	1990-10-29	1991-10-29	Derives du thienoimidazole, leurs production et leur utilisation

Country Status (1)

Country	Link
CA (1)	CA2054465A1 (fr)

1991
- 1991-10-29 CA CA 2054465 patent/CA2054465A1/fr not_active Abandoned

Legal Events

Date	Code	Title	Description
1998-10-07	EEER	Examination request
2005-04-11	FZDE	Dead

Publication	Publication Date	Title
US5463073A (en)	1995-10-31	Thienoimidazole derivatives, their production and use
US5703110A (en)	1997-12-30	Benzimidazole derivatives, their production and use
CA2204290C (fr)	2001-12-18	Derives du benzimidazole; production et utilisation
US5162326A (en)	1992-11-10	Pyrimidinedione derivatives, their production and use
US5243054A (en)	1993-09-07	Compound which is angiotensin ii antagonist
US6004989A (en)	1999-12-21	Benzimidazole derivatives, their production and use
EP0434038A1 (fr)	1991-06-26	Dérivés condensés d'imidazole, leur préparation et leur utilisation
NO179283B (no)	1996-06-03	Analogifremgangsmåte for fremstilling av terapeutisk aktive substituerte azoler
EP0588299B1 (fr)	1998-07-01	Dérivés de 1,2,4-oxadiazolyl ou de 1,2,4-thiadiazolyl-biphényl comme antagonistes d'angiotensine II
JPH05186462A (ja)	1993-07-27	複素環式化合物、その製造方法および該化合物を含有する高血圧症およびうつ血性心麻痺用の医薬調剤
JP3099096B2 (ja)	2000-10-16	チエノイミダゾール誘導体
RU2052455C1 (ru)	1996-01-20	Производные бензимидазола их фармацевтически приемлемые соли стабильный кристалл и композиция для ингибирования ангиотензина ii
RU2144022C1 (ru)	2000-01-10	Эфиры n-(бифенилметил)аминобензойной кислоты и способ их получения
IL97882A (en)	1996-11-14	N-aralkylbenzimidazole derivatives their production and pharmaceutical compositions containing them
SK282473B6 (sk)	2002-02-05	Benzimidazolová zlúčenina a spôsob jej prípravy, stabilný kryštál, farmaceutický prípravok a medziprodukt