DK174948B1 - Antihypertensive forbindelser, farmaceutisk præparat indeholdende en sådan forbindelse, anvendelse af forbindelserne til fremstilling af et lægemiddel samt fremgangsmåde til fremstilling af forbindelserne - Google Patents
Antihypertensive forbindelser, farmaceutisk præparat indeholdende en sådan forbindelse, anvendelse af forbindelserne til fremstilling af et lægemiddel samt fremgangsmåde til fremstilling af forbindelserne Download PDFInfo
- Publication number
- DK174948B1 DK174948B1 DK198900051A DK5189A DK174948B1 DK 174948 B1 DK174948 B1 DK 174948B1 DK 198900051 A DK198900051 A DK 198900051A DK 5189 A DK5189 A DK 5189A DK 174948 B1 DK174948 B1 DK 174948B1
- Authority
- DK
- Denmark
- Prior art keywords
- butyl
- imidazole
- methyl
- nmr
- chloro
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 166
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title claims description 221
- 150000001875 compounds Chemical class 0.000 title claims description 143
- 239000003814 drug Substances 0.000 title claims description 11
- 239000002220 antihypertensive agent Substances 0.000 title claims description 10
- 229940079593 drug Drugs 0.000 title description 8
- 239000002934 diuretic Substances 0.000 claims abstract description 14
- 230000001882 diuretic effect Effects 0.000 claims abstract description 11
- 230000003276 anti-hypertensive effect Effects 0.000 claims abstract description 9
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims abstract description 9
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- 230000008569 process Effects 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 166
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- 239000002904 solvent Substances 0.000 claims description 110
- 238000006243 chemical reaction Methods 0.000 claims description 101
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- KKKDZZRICRFGSD-UHFFFAOYSA-N 1-benzylimidazole Chemical compound C1=CN=CN1CC1=CC=CC=C1 KKKDZZRICRFGSD-UHFFFAOYSA-N 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 26
- 238000010992 reflux Methods 0.000 claims description 24
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
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- 150000003839 salts Chemical class 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 206010020772 Hypertension Diseases 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 3
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical group C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 2
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- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical class CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 1
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- KPMAPYWGVVZFGY-HTQZYQBOSA-N ethyl (1r,2r)-2-(trifluoromethylsulfonylamino)cyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCC[C@H]1NS(=O)(=O)C(F)(F)F KPMAPYWGVVZFGY-HTQZYQBOSA-N 0.000 description 1
- VODUKXHGDCJEOZ-HTQZYQBOSA-N ethyl (1r,2r)-2-aminocyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCC[C@H]1N VODUKXHGDCJEOZ-HTQZYQBOSA-N 0.000 description 1
- AEIFFTVPAFUZJC-UHFFFAOYSA-N ethyl 2-(4-methylbenzoyl)-4-oxobutanoate Chemical compound CCOC(=O)C(CC=O)C(=O)C1=CC=C(C)C=C1 AEIFFTVPAFUZJC-UHFFFAOYSA-N 0.000 description 1
- LNXJXSGTLAYHQS-UHFFFAOYSA-N ethyl 2-(4-methylphenyl)benzoate Chemical compound CCOC(=O)C1=CC=CC=C1C1=CC=C(C)C=C1 LNXJXSGTLAYHQS-UHFFFAOYSA-N 0.000 description 1
- GEQMJBPKCOZHMV-UHFFFAOYSA-N ethyl 3-(4-methylphenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=C(C)C=C1 GEQMJBPKCOZHMV-UHFFFAOYSA-N 0.000 description 1
- USZCXXUVCXVGGF-UHFFFAOYSA-N ethyl 3-[3-[(4-aminophenyl)methyl]-2-butyl-5-chloroimidazol-4-yl]prop-2-enoate Chemical compound CCCCC1=NC(Cl)=C(C=CC(=O)OCC)N1CC1=CC=C(N)C=C1 USZCXXUVCXVGGF-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-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
- 238000002474 experimental method Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000019382 gum benzoic Nutrition 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 238000006698 hydrazinolysis reaction Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007031 hydroxymethylation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- VQYGGVWYIFZILX-UHFFFAOYSA-N imidazol-1-yl(phenyl)methanamine Chemical class C1=CN=CN1C(N)C1=CC=CC=C1 VQYGGVWYIFZILX-UHFFFAOYSA-N 0.000 description 1
- PRJKNHOMHKJCEJ-UHFFFAOYSA-N imidazol-4-ylacetic acid Chemical class OC(=O)CC1=CN=CN1 PRJKNHOMHKJCEJ-UHFFFAOYSA-N 0.000 description 1
- 150000007928 imidazolide derivatives Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002496 iodine Chemical class 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 159000000014 iron salts Chemical class 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- AKSNADLMBMHWNT-UHFFFAOYSA-N lithium;tris(2,2,2-trimethoxyethoxy)alumane Chemical compound [Li].COC(OC)(OC)CO[Al](OCC(OC)(OC)OC)OCC(OC)(OC)OC AKSNADLMBMHWNT-UHFFFAOYSA-N 0.000 description 1
- 125000003564 m-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(C#N)=C1[H])C([H])([H])* 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 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
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 229940013798 meclofenamate Drugs 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-M meclofenamic acid(1-) Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C([O-])=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-M 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- YVWLZDNTMKCRDP-UHFFFAOYSA-N methyl 1-[[2-butyl-5-chloro-3-[[4-(2-methoxycarbonylbenzoyl)phenyl]methyl]imidazol-4-yl]methyl]triazole-4-carboxylate Chemical compound C=1C=C(C(=O)C=2C(=CC=CC=2)C(=O)OC)C=CC=1CN1C(CCCC)=NC(Cl)=C1CN1C=C(C(=O)OC)N=N1 YVWLZDNTMKCRDP-UHFFFAOYSA-N 0.000 description 1
- CURCXTFZSFUUQT-UHFFFAOYSA-N methyl 2-(1h-imidazol-5-yl)acetate Chemical compound COC(=O)CC1=CNC=N1 CURCXTFZSFUUQT-UHFFFAOYSA-N 0.000 description 1
- CYFOMARCXDOJCV-UHFFFAOYSA-N methyl 2-(2-methylphenyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1C1=CC=CC=C1C CYFOMARCXDOJCV-UHFFFAOYSA-N 0.000 description 1
- VPHCHUGAUUMEJU-UHFFFAOYSA-N methyl 2-[2-butyl-4-chloro-3-[(4-nitrophenyl)methyl]-2h-imidazol-4-yl]acetate Chemical compound CCCCC1N=CC(Cl)(CC(=O)OC)N1CC1=CC=C([N+]([O-])=O)C=C1 VPHCHUGAUUMEJU-UHFFFAOYSA-N 0.000 description 1
- SXEWQLHTVROZQE-UHFFFAOYSA-N methyl 2-[2-butyl-5-chloro-3-[[4-(trifluoromethylsulfonylamino)phenyl]methyl]imidazol-4-yl]acetate Chemical compound CCCCC1=NC(Cl)=C(CC(=O)OC)N1CC1=CC=C(NS(=O)(=O)C(F)(F)F)C=C1 SXEWQLHTVROZQE-UHFFFAOYSA-N 0.000 description 1
- TWUJKYFPPSDBMW-UHFFFAOYSA-N methyl 2-[3-[[4-(benzylamino)phenyl]methyl]-2-butyl-5-chloroimidazol-4-yl]acetate Chemical compound CCCCC1=NC(Cl)=C(CC(=O)OC)N1CC(C=C1)=CC=C1NCC1=CC=CC=C1 TWUJKYFPPSDBMW-UHFFFAOYSA-N 0.000 description 1
- OHHITJYTTZWFBQ-UHFFFAOYSA-N methyl 2-[4-(aminomethyl)phenyl]benzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=CC=C1C1=CC=C(CN)C=C1 OHHITJYTTZWFBQ-UHFFFAOYSA-N 0.000 description 1
- UOLMZWZSLYSILW-UHFFFAOYSA-N methyl 2-[4-(azidomethyl)phenyl]benzoate Chemical group COC(=O)C1=CC=CC=C1C1=CC=C(CN=[N+]=[N-])C=C1 UOLMZWZSLYSILW-UHFFFAOYSA-N 0.000 description 1
- QTAFIJHJKANVIY-UHFFFAOYSA-N methyl 2-[4-(bromomethyl)benzoyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1C(=O)C1=CC=C(CBr)C=C1 QTAFIJHJKANVIY-UHFFFAOYSA-N 0.000 description 1
- SNOJXQJHQJCIAJ-RUDMXATFSA-N methyl 2-[4-[[2-[(e)-but-1-enyl]-4-chloro-5-(hydroxymethyl)imidazol-1-yl]methyl]phenyl]benzoate Chemical compound CC\C=C\C1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 SNOJXQJHQJCIAJ-RUDMXATFSA-N 0.000 description 1
- BRVFTRIBYNPXJB-RUDMXATFSA-N methyl 2-[4-[[2-[(e)-but-1-enyl]-4-chloro-5-formylimidazol-1-yl]methyl]phenyl]benzoate Chemical compound CC\C=C\C1=NC(Cl)=C(C=O)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 BRVFTRIBYNPXJB-RUDMXATFSA-N 0.000 description 1
- FYDYFKUSTFJPLP-UHFFFAOYSA-N methyl 2-[4-[[2-butyl-4-chloro-5-(1,2,4-triazol-1-ylmethyl)imidazol-1-yl]methyl]benzoyl]benzoate Chemical compound C=1C=C(C(=O)C=2C(=CC=CC=2)C(=O)OC)C=CC=1CN1C(CCCC)=NC(Cl)=C1CN1C=NC=N1 FYDYFKUSTFJPLP-UHFFFAOYSA-N 0.000 description 1
- OXINGWAPUCLVLL-UHFFFAOYSA-N methyl 2-[4-[[2-butyl-4-chloro-5-(2-methoxyethoxymethoxymethyl)imidazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCCC1=NC(Cl)=C(COCOCCOC)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 OXINGWAPUCLVLL-UHFFFAOYSA-N 0.000 description 1
- IKVORIYGRZUZKQ-UHFFFAOYSA-N methyl 2-[4-[[2-butyl-4-chloro-5-(2h-tetrazol-5-ylmethyl)imidazol-1-yl]methyl]benzoyl]benzoate Chemical compound C=1C=C(C(=O)C=2C(=CC=CC=2)C(=O)OC)C=CC=1CN1C(CCCC)=NC(Cl)=C1CC1=NN=NN1 IKVORIYGRZUZKQ-UHFFFAOYSA-N 0.000 description 1
- FUYHVVFRMPDPPE-UHFFFAOYSA-N methyl 2-[4-[[2-butyl-4-chloro-5-(3-oxobut-1-enyl)imidazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCCC1=NC(Cl)=C(C=CC(C)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 FUYHVVFRMPDPPE-UHFFFAOYSA-N 0.000 description 1
- GTUYTJKPGMABIY-UHFFFAOYSA-N methyl 2-[4-[[2-butyl-4-chloro-5-(chloromethyl)imidazol-1-yl]methyl]benzoyl]benzoate;hydrochloride Chemical compound Cl.CCCCC1=NC(Cl)=C(CCl)N1CC1=CC=C(C(=O)C=2C(=CC=CC=2)C(=O)OC)C=C1 GTUYTJKPGMABIY-UHFFFAOYSA-N 0.000 description 1
- KHKKWUAAYXZQLG-UHFFFAOYSA-N methyl 2-[4-[[2-butyl-4-chloro-5-(cyanomethyl)imidazol-1-yl]methyl]benzoyl]benzoate Chemical compound CCCCC1=NC(Cl)=C(CC#N)N1CC1=CC=C(C(=O)C=2C(=CC=CC=2)C(=O)OC)C=C1 KHKKWUAAYXZQLG-UHFFFAOYSA-N 0.000 description 1
- KNWIRLDRLOBLQZ-UHFFFAOYSA-N methyl 2-[4-[[2-butyl-4-chloro-5-[(naphthalen-1-ylcarbamoylamino)methyl]imidazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCCC1=NC(Cl)=C(CNC(=O)NC=2C3=CC=CC=C3C=CC=2)N1CC(C=C1)=CC=C1C1=CC=CC=C1C(=O)OC KNWIRLDRLOBLQZ-UHFFFAOYSA-N 0.000 description 1
- AKZHHJDHPFWPPW-UHFFFAOYSA-N methyl 2-[4-[[2-butyl-4-chloro-5-[(trifluoromethylsulfonylamino)methyl]imidazol-1-yl]methyl]benzoyl]benzoate Chemical compound CCCCC1=NC(Cl)=C(CNS(=O)(=O)C(F)(F)F)N1CC1=CC=C(C(=O)C=2C(=CC=CC=2)C(=O)OC)C=C1 AKZHHJDHPFWPPW-UHFFFAOYSA-N 0.000 description 1
- LJPOORABHDJSHF-UHFFFAOYSA-N methyl 2-[4-[[5-(aminomethyl)-2-butyl-4-chloroimidazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCCC1=NC(Cl)=C(CN)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 LJPOORABHDJSHF-UHFFFAOYSA-N 0.000 description 1
- BLXXSZJPPANHJW-UHFFFAOYSA-N methyl 2-[4-[[5-(azidomethyl)-2-butyl-4-chloroimidazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCCC1=NC(Cl)=C(CN=[N+]=[N-])N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 BLXXSZJPPANHJW-UHFFFAOYSA-N 0.000 description 1
- XUUHGFSFNGRULP-UHFFFAOYSA-N methyl 3-[2-butyl-5-chloro-3-[(4-nitrophenyl)methyl]imidazol-4-yl]propanoate Chemical compound CCCCC1=NC(Cl)=C(CCC(=O)OC)N1CC1=CC=C([N+]([O-])=O)C=C1 XUUHGFSFNGRULP-UHFFFAOYSA-N 0.000 description 1
- LLXZURAYELTYRD-UHFFFAOYSA-N methyl 3-[4-[[2-butyl-4-chloro-5-(methoxymethyl)imidazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCCC1=NC(Cl)=C(COC)N1CC1=CC=C(C=2C=C(C=CC=2)C(=O)OC)C=C1 LLXZURAYELTYRD-UHFFFAOYSA-N 0.000 description 1
- UHNVFVSKUDKAKQ-UHFFFAOYSA-N methyl 3-[[2-butyl-5-chloro-3-[[4-(2-methoxycarbonylbenzoyl)phenyl]methyl]imidazol-4-yl]methyl]triazole-4-carboxylate Chemical compound C=1C=C(C(=O)C=2C(=CC=CC=2)C(=O)OC)C=CC=1CN1C(CCCC)=NC(Cl)=C1CN1N=NC=C1C(=O)OC UHNVFVSKUDKAKQ-UHFFFAOYSA-N 0.000 description 1
- NPXOIGSBRLCOSD-UHFFFAOYSA-N methyl 3-iodobenzoate Chemical compound COC(=O)C1=CC=CC(I)=C1 NPXOIGSBRLCOSD-UHFFFAOYSA-N 0.000 description 1
- SATDLKYRVXFXRE-UHFFFAOYSA-N methyl 4-(chloromethyl)benzoate Chemical compound COC(=O)C1=CC=C(CCl)C=C1 SATDLKYRVXFXRE-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 150000005217 methyl ethers Chemical class 0.000 description 1
- IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 description 1
- YNLFEVAOQLXINF-UHFFFAOYSA-N methylsulfanylmethane;tribromoborane Chemical compound CSC.BrB(Br)Br YNLFEVAOQLXINF-UHFFFAOYSA-N 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
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- AAYWQUFITSQGLP-UHFFFAOYSA-N n-[2-[4-[[2-butyl-4-chloro-5-(hydroxymethyl)imidazol-1-yl]methyl]phenyl]phenyl]-2,2,2-trifluoroacetamide Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)NC(=O)C(F)(F)F)C=C1 AAYWQUFITSQGLP-UHFFFAOYSA-N 0.000 description 1
- ZPPIDMIQFKCAJE-UHFFFAOYSA-N n-[2-[4-[[2-butyl-4-chloro-5-(methoxymethyl)imidazol-1-yl]methyl]phenyl]phenyl]-1,1,1-trifluoromethanesulfonamide Chemical compound CCCCC1=NC(Cl)=C(COC)N1CC1=CC=C(C=2C(=CC=CC=2)NS(=O)(=O)C(F)(F)F)C=C1 ZPPIDMIQFKCAJE-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
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- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- RPMXALUWKZHYOV-UHFFFAOYSA-N nitroethene Chemical group [O-][N+](=O)C=C RPMXALUWKZHYOV-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- YSIMAPNUZAVQER-UHFFFAOYSA-N octanenitrile Chemical compound CCCCCCCC#N YSIMAPNUZAVQER-UHFFFAOYSA-N 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 150000002918 oxazolines Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
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- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical class C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
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- FFNMBRCFFADNAO-UHFFFAOYSA-N pirenzepine hydrochloride Chemical compound [H+].[H+].[Cl-].[Cl-].C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 FFNMBRCFFADNAO-UHFFFAOYSA-N 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000010289 potassium nitrite Nutrition 0.000 description 1
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- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- BEBPTRYPELOERP-UHFFFAOYSA-M potassium;methanethiolate Chemical compound [K+].[S-]C BEBPTRYPELOERP-UHFFFAOYSA-M 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002315 pressor effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical compound [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 229940070891 pyridium Drugs 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 238000012958 reprocessing Methods 0.000 description 1
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- 238000012552 review Methods 0.000 description 1
- FCQRKDSALKMOGU-UHFFFAOYSA-K rhodium(3+);triphenylphosphane;trichloride Chemical compound Cl[Rh](Cl)Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 FCQRKDSALKMOGU-UHFFFAOYSA-K 0.000 description 1
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- 239000012047 saturated solution Substances 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
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- 229910052710 silicon Inorganic materials 0.000 description 1
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- 235000009518 sodium iodide Nutrition 0.000 description 1
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- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
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- OWEDFWZJRNPJIV-UHFFFAOYSA-N tert-butyl 2-(4-methylphenyl)benzoate Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1C(=O)OC(C)(C)C OWEDFWZJRNPJIV-UHFFFAOYSA-N 0.000 description 1
- CQEMEPYXTZSQDS-UHFFFAOYSA-N tert-butyl 2-[4-[[2-butyl-5-(hydroxymethyl)-4-iodoimidazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCCC1=NC(I)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC(C)(C)C)C=C1 CQEMEPYXTZSQDS-UHFFFAOYSA-N 0.000 description 1
- ANBACSHPNLVDPC-UHFFFAOYSA-N tert-butyl 2-[4-[[2-butyl-5-(hydroxymethyl)-4-nitroimidazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCCC1=NC([N+]([O-])=O)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC(C)(C)C)C=C1 ANBACSHPNLVDPC-UHFFFAOYSA-N 0.000 description 1
- WOQMYWUAPXRZQS-UHFFFAOYSA-N tert-butyl 3-(4-methylphenyl)benzoate Chemical compound C1=CC(C)=CC=C1C1=CC=CC(C(=O)OC(C)(C)C)=C1 WOQMYWUAPXRZQS-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
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- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 125000005490 tosylate group Chemical group 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
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 229940032178 vaseretic Drugs 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- 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
- C07D233/64—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 substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- 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
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- 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
- C07D233/66—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/68—Halogen atoms
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- 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
- C07D233/66—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/70—One oxygen atom
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- 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
- C07D233/66—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
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- 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
- C07D233/66—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
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- 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
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Biochemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14258088A | 1988-01-07 | 1988-01-07 | |
US14258088 | 1988-01-07 | ||
US07/279,194 US5138069A (en) | 1986-07-11 | 1988-12-06 | Angiotensin II receptor blocking imidazoles |
US27919488 | 1988-12-06 |
Publications (3)
Publication Number | Publication Date |
---|---|
DK5189D0 DK5189D0 (da) | 1989-01-06 |
DK5189A DK5189A (da) | 1989-07-08 |
DK174948B1 true DK174948B1 (da) | 2004-03-15 |
Family
ID=26840231
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK198900051A DK174948B1 (da) | 1988-01-07 | 1989-01-06 | Antihypertensive forbindelser, farmaceutisk præparat indeholdende en sådan forbindelse, anvendelse af forbindelserne til fremstilling af et lægemiddel samt fremgangsmåde til fremstilling af forbindelserne |
Country Status (20)
Country | Link |
---|---|
EP (1) | EP0324377B1 (fi) |
JP (1) | JPH0725738B2 (fi) |
AT (2) | ATE164520T1 (fi) |
AU (1) | AU617736B2 (fi) |
CA (1) | CA1338238C (fi) |
CY (2) | CY2187B1 (fi) |
DE (3) | DE19875033I2 (fi) |
DK (1) | DK174948B1 (fi) |
ES (2) | ES2117463T3 (fi) |
FI (1) | FI99012C (fi) |
GR (1) | GR3024053T3 (fi) |
HU (1) | HU211317A9 (fi) |
IE (2) | IE81569B1 (fi) |
IL (1) | IL88900A0 (fi) |
LU (1) | LU90266I2 (fi) |
NO (1) | NO177265C (fi) |
NZ (1) | NZ227539A (fi) |
PT (1) | PT89401B (fi) |
RU (2) | RU1814646C (fi) |
WO (1) | WO1989006233A1 (fi) |
Families Citing this family (179)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4820843A (en) * | 1987-05-22 | 1989-04-11 | E. I. Du Pont De Nemours And Company | Tetrazole intermediates to antihypertensive compounds |
US5210079A (en) * | 1988-01-07 | 1993-05-11 | E. I. Du Pont De Nemours And Company | Treatment of chronic renal failure with imidazole angiotensin-II receptor antagonists |
CA2003283A1 (en) * | 1988-12-05 | 1990-06-05 | C. Anne Higley | Imidazoles for the treatment of atherosclerosis |
US5354867A (en) * | 1988-12-06 | 1994-10-11 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking imidazoles |
US5185351A (en) * | 1989-06-14 | 1993-02-09 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids useful as angiotensin II receptor antagonists |
US5418250A (en) * | 1989-06-14 | 1995-05-23 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids useful as angiotensin II receptor antagonists |
DK0403159T3 (da) * | 1989-06-14 | 2000-08-14 | Smithkline Beecham Corp | Imidazolylalkensyrer |
US5312828A (en) * | 1989-06-14 | 1994-05-17 | Finkelstein Joseph A | Substituted imidazoles having angiotensin II receptor blocking activity |
EP0403158A3 (en) * | 1989-06-14 | 1991-12-18 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids |
JP2550442B2 (ja) * | 1989-06-30 | 1996-11-06 | イー・アイ・デュポン・ドゥ・ヌムール・アンド・カンパニー | 置換イミダゾール |
EP0479892A1 (en) * | 1989-06-30 | 1992-04-15 | E.I. Du Pont De Nemours And Company | Fused-ring aryl substituted imidazoles |
ATE113281T1 (de) * | 1989-08-02 | 1994-11-15 | Takeda Chemical Industries Ltd | Pyrazol-derivate, verfahren zu deren herstellung und anwendung. |
US5100897A (en) * | 1989-08-28 | 1992-03-31 | Merck & Co., Inc. | Substituted pyrimidinones as angiotensin ii antagonists |
AU621245B2 (en) * | 1989-10-17 | 1992-03-05 | Boehringer Mannheim Gmbh | Hydrolase substrates, a process for the preparation thereof and agents containing them |
AU640417B2 (en) * | 1989-10-25 | 1993-08-26 | Smithkline Beecham Corporation | Substituted 5-((tetrazolyl)alkenyl)imidazoles |
CA2028925A1 (en) * | 1989-11-06 | 1991-05-07 | Gerald R. Girard | Substituted n-(imidazolyl)alkyl alanine derivatives |
US5248689A (en) * | 1989-11-06 | 1993-09-28 | Smithkline Beecham Corporation | Substituted N-(imidazolyl)alkyl alanine derivatives |
US5073566A (en) * | 1989-11-30 | 1991-12-17 | Eli Lilly And Company | Angiotensin ii antagonist 1,3-imidazoles and use thereas |
US5104891A (en) * | 1989-12-11 | 1992-04-14 | G. D. Searle & Co. | Cycloheptimidazolone compounds as angiotensin ii antagonists for control of hypertension |
EP0557276A1 (en) * | 1989-12-29 | 1993-09-01 | University Technologies International Inc. (Uti) | Methods for modelling tertiary structures of biologically active ligands including agonists and antagonists thereto and novel synthetic antagonists based on angiotensin |
US5234917A (en) * | 1989-12-29 | 1993-08-10 | Finkelstein Joseph A | Substituted 5-(alkyl)carboxamide imidazoles |
JPH05503691A (ja) * | 1989-12-29 | 1993-06-17 | ユニバーシティ・テクノロジーズ・インターナショナル・インコーポレイテッド | アゴニストおよびアンタゴニストを含む生物学的に活性なリガンドの3次構造モデルの設計方法およびアンギオテンシンに基づいた新規合成アンタゴニスト |
US5449682A (en) * | 1990-02-13 | 1995-09-12 | Merck & Co., Inc. | Angiotensin II antagonists incorporating a substituted benzyl element |
US5183810A (en) * | 1990-02-13 | 1993-02-02 | Merck & Co., Inc. | Imidazole angiotensin II antagonists incorporating a substituted benzyl element |
US5240938A (en) * | 1991-02-13 | 1993-08-31 | Merck & Co., Inc. | Angiotensin II antagonists incorporating a substituted pyridoimidazolyl ring |
PH30484A (en) * | 1990-02-19 | 1997-05-28 | Ciba Geigy | Acy compounds pharmaceutical composition containing said compound and method of use thereof |
KR910021381A (ko) * | 1990-02-20 | 1991-12-20 | 모리 히데오 | 4-3급 부틸이미다졸 유도체, 및 이의 제조방법 및 용도 |
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DK531479A (da) | 1979-01-19 | 1980-07-20 | Pfizer | Fremgangsmaade til fremstilling af imidazolderivater og salte deraf |
JPS5671074A (en) * | 1979-11-12 | 1981-06-13 | Takeda Chem Ind Ltd | 1,2-disubstituted-4-halogenoimidazole-5-acetic acid derivative |
JPS5671073A (en) * | 1979-11-12 | 1981-06-13 | Takeda Chem Ind Ltd | Imidazole derivative |
DE3106150A1 (de) | 1981-02-13 | 1982-09-16 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | "verfahren zur herstellung von imidazolessigsaeurederivaten" |
JPS58157768A (ja) * | 1982-03-16 | 1983-09-19 | Takeda Chem Ind Ltd | 4−クロロ−2−フエニルイミダゾ−ル−5−酢酸誘導体 |
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US4532331A (en) * | 1983-04-12 | 1985-07-30 | Smithkline Beckman Corporation | 1-Benzyl-2-aminomethyl imidazole derivatives |
FI833794A0 (fi) | 1983-10-18 | 1983-10-18 | Farmos Oy | Substituerade 2-merkapto-imidazoler |
US4755518A (en) * | 1985-12-20 | 1988-07-05 | Warner-Lambert Company | Imidazolyl or tetrazolyl substituted benzoic acid derivatives and pharmaceutical compositions thereof |
EP0235310B1 (de) | 1986-02-04 | 1989-12-13 | Institut Po Metalokeramika | Legierung zum Aufschweissen |
CA1334092C (en) * | 1986-07-11 | 1995-01-24 | David John Carini | Angiotensin ii receptor blocking imidazoles |
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EP0403158A3 (en) * | 1989-06-14 | 1991-12-18 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids |
-
1988
- 1988-12-22 CA CA000586904A patent/CA1338238C/en not_active Expired - Lifetime
-
1989
- 1989-01-05 DE DE1998175033 patent/DE19875033I2/de active Active
- 1989-01-05 ES ES96107930T patent/ES2117463T3/es not_active Expired - Lifetime
- 1989-01-05 EP EP89100144A patent/EP0324377B1/en not_active Expired - Lifetime
- 1989-01-05 NZ NZ227539A patent/NZ227539A/en unknown
- 1989-01-05 AT AT96107930T patent/ATE164520T1/de active
- 1989-01-05 DE DE68927965T patent/DE68927965T2/de not_active Expired - Lifetime
- 1989-01-05 WO PCT/US1989/000052 patent/WO1989006233A1/en unknown
- 1989-01-05 ES ES89100144T patent/ES2100150T3/es not_active Expired - Lifetime
- 1989-01-05 DE DE68928631T patent/DE68928631T2/de not_active Expired - Lifetime
- 1989-01-05 AT AT89100144T patent/ATE151755T1/de not_active IP Right Cessation
- 1989-01-05 JP JP50165689A patent/JPH0725738B2/ja not_active Expired - Lifetime
- 1989-01-06 NO NO890075A patent/NO177265C/no not_active IP Right Cessation
- 1989-01-06 PT PT89401A patent/PT89401B/pt not_active IP Right Cessation
- 1989-01-06 RU SU894613475A patent/RU1814646C/ru active
- 1989-01-06 FI FI890070A patent/FI99012C/fi not_active IP Right Cessation
- 1989-01-06 AU AU27771/89A patent/AU617736B2/en not_active Expired
- 1989-01-06 IL IL88900A patent/IL88900A0/xx unknown
- 1989-01-06 DK DK198900051A patent/DK174948B1/da not_active IP Right Cessation
- 1989-01-09 IE IE4589A patent/IE81569B1/en not_active IP Right Cessation
- 1989-01-09 IE IE960772A patent/IE82833B1/en not_active IP Right Cessation
-
1992
- 1992-01-27 RU SU925010637A patent/RU2017733C1/ru active
-
1995
- 1995-06-30 HU HU95P/P00636P patent/HU211317A9/hu unknown
-
1997
- 1997-07-09 GR GR970401708T patent/GR3024053T3/el unknown
-
1998
- 1998-07-29 LU LU90266C patent/LU90266I2/fr unknown
-
1999
- 1999-03-04 CY CY9900010A patent/CY2187B1/xx unknown
-
2004
- 2004-07-08 CY CY2004001C patent/CY2004001I2/el unknown
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PUP | Patent expired |