NO300326B1 - Imidazo-annelerte iso- og heterocykliske forbindelser og deres anvendelse - Google Patents
Imidazo-annelerte iso- og heterocykliske forbindelser og deres anvendelse Download PDFInfo
- Publication number
- NO300326B1 NO300326B1 NO923535A NO923535A NO300326B1 NO 300326 B1 NO300326 B1 NO 300326B1 NO 923535 A NO923535 A NO 923535A NO 923535 A NO923535 A NO 923535A NO 300326 B1 NO300326 B1 NO 300326B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- imidazo
- methyl
- mmol
- sio
- Prior art date
Links
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 235
- 102000008873 Angiotensin II receptor Human genes 0.000 claims abstract description 8
- 108050000824 Angiotensin II receptor Proteins 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical group C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 3
- 230000003042 antagnostic effect Effects 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 239000005557 antagonist Substances 0.000 abstract description 4
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 abstract 1
- 125000006413 ring segment Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
- 239000000243 solution Substances 0.000 description 78
- 229910004298 SiO 2 Inorganic materials 0.000 description 70
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 52
- 238000000034 method Methods 0.000 description 51
- 238000002844 melting Methods 0.000 description 40
- 230000008018 melting Effects 0.000 description 40
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 29
- 229910052681 coesite Inorganic materials 0.000 description 28
- 229910052906 cristobalite Inorganic materials 0.000 description 28
- 229910052682 stishovite Inorganic materials 0.000 description 28
- 229910052905 tridymite Inorganic materials 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- 238000004587 chromatography analysis Methods 0.000 description 22
- 239000011734 sodium Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- -1 benzyl halide Chemical class 0.000 description 17
- 239000000460 chlorine Substances 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 12
- 235000012239 silicon dioxide Nutrition 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 229950006323 angiotensin ii Drugs 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 125000004076 pyridyl group Chemical group 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 102000005862 Angiotensin II Human genes 0.000 description 7
- 101800000733 Angiotensin-2 Proteins 0.000 description 7
- 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 7
- 238000009835 boiling Methods 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 239000002287 radioligand Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- JJPIVRWTAGQTPQ-UHFFFAOYSA-N 2-amino-3-nitrobenzoic acid Chemical compound NC1=C(C(O)=O)C=CC=C1[N+]([O-])=O JJPIVRWTAGQTPQ-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 235000015320 potassium carbonate Nutrition 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- XWWJWZJOSWSJQV-UHFFFAOYSA-N 2-ethyl-5,7-dimethyl-1h-imidazo[4,5-b]pyridine Chemical compound CC1=CC(C)=C2NC(CC)=NC2=N1 XWWJWZJOSWSJQV-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- 210000004100 adrenal gland Anatomy 0.000 description 3
- HXBPYFMVGFDZFT-UHFFFAOYSA-N allyl isocyanate Chemical compound C=CCN=C=O HXBPYFMVGFDZFT-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- AOCYHPQXGJBAQQ-UHFFFAOYSA-N ethyl n-sulfonylcarbamate Chemical group CCOC(=O)N=S(=O)=O AOCYHPQXGJBAQQ-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000700 radioactive tracer Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
- LGPFFMMQIUXISP-UHFFFAOYSA-N 1-[2-[4-[(2-ethyl-7-methylimidazo[4,5-b]pyridin-3-yl)methyl]phenyl]phenyl]sulfonyl-3-propylurea Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=CC=C1C(C=C1)=CC=C1CN1C2=NC=CC(C)=C2N=C1CC LGPFFMMQIUXISP-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- BZKBOWJBYJIIDF-UHFFFAOYSA-N 2-butyl-3-[(2-carboxy-3-chloro-1-benzothiophen-6-yl)methyl]benzimidazole-4-carboxylic acid Chemical compound C1=C2C(Cl)=C(C(O)=O)SC2=CC(CN2C3=C(C(O)=O)C=CC=C3N=C2CCCC)=C1 BZKBOWJBYJIIDF-UHFFFAOYSA-N 0.000 description 2
- HJYAVTRUWVKPII-UHFFFAOYSA-N 2-butyl-3-[(3-carboxy-2-phenylimidazo[1,2-a]pyridin-7-yl)methyl]benzimidazole-4-carboxylic acid Chemical compound CCCCC1=NC2=CC=CC(C(O)=O)=C2N1CC(=CC1=N2)C=CN1C(C(O)=O)=C2C1=CC=CC=C1 HJYAVTRUWVKPII-UHFFFAOYSA-N 0.000 description 2
- HCGMSNZSEBWVOU-UHFFFAOYSA-N 2-butyl-3-[[4-[2-(ethoxycarbonylsulfamoyl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid Chemical compound CCCCC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)OCC HCGMSNZSEBWVOU-UHFFFAOYSA-N 0.000 description 2
- CWFXHNDKWWQWEB-UHFFFAOYSA-N 2-butyl-3-[[4-[2-(ethylcarbamoylsulfamoyl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid Chemical compound CCCCC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)NCC CWFXHNDKWWQWEB-UHFFFAOYSA-N 0.000 description 2
- SCXGFWVSSJTXBF-UHFFFAOYSA-N 2-ethyl-7-methyl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CN=C2NC(CC)=NC2=C1C SCXGFWVSSJTXBF-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- NFFJKLKIAFVKEX-UHFFFAOYSA-N 7-[(2-butyl-7-carboxybenzimidazol-1-yl)methyl]-2-phenylimidazo[1,2-a]pyrimidine-3-carboxylic acid Chemical compound CCCCC1=NC2=CC=CC(C(O)=O)=C2N1CC(=NC1=N2)C=CN1C(C(O)=O)=C2C1=CC=CC=C1 NFFJKLKIAFVKEX-UHFFFAOYSA-N 0.000 description 2
- FZZOEWNUHXOMRZ-UHFFFAOYSA-N 7-[(2-butylimidazo[4,5-b]pyridin-3-yl)methyl]-2-phenylimidazo[1,2-a]pyridine-3-carboxylic acid Chemical compound CCCCC1=NC2=CC=CN=C2N1CC(=CC1=N2)C=CN1C(C(O)=O)=C2C1=CC=CC=C1 FZZOEWNUHXOMRZ-UHFFFAOYSA-N 0.000 description 2
- KWEPMUXSOLDTON-UHFFFAOYSA-N 7-[(2-butylimidazo[4,5-b]pyridin-3-yl)methyl]-2-phenylimidazo[1,2-a]pyrimidine-3-carboxylic acid Chemical compound CCCCC1=NC2=CC=CN=C2N1CC(=NC1=N2)C=CN1C(C(O)=O)=C2C1=CC=CC=C1 KWEPMUXSOLDTON-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- 108010064733 Angiotensins Proteins 0.000 description 2
- 108010039627 Aprotinin Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 125000006267 biphenyl group Chemical group 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000004316 dimethyl dicarbonate Substances 0.000 description 2
- 235000010300 dimethyl dicarbonate Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical class [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 125000000565 sulfonamide group Chemical group 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical group OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- HTGQCLJTWPSFNL-UHFFFAOYSA-N (2-methylphenoxy)boronic acid Chemical compound CC1=CC=CC=C1OB(O)O HTGQCLJTWPSFNL-UHFFFAOYSA-N 0.000 description 1
- LCYNVXWUUNVJIS-UHFFFAOYSA-N 1-(aminomethyl)-n-[2-[4-[(2-ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-yl)methyl]phenyl]phenyl]sulfonylcyclohexane-1-carboxamide Chemical compound CCC1=NC2=C(C)C=C(C)N=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)C1(CN)CCCCC1 LCYNVXWUUNVJIS-UHFFFAOYSA-N 0.000 description 1
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- IDEFXINQQGAPPA-UHFFFAOYSA-N 1-ethyl-3-[2-[4-[(2-ethyl-7-methylimidazo[4,5-b]pyridin-3-yl)methyl]phenyl]phenyl]sulfonylurea Chemical compound CCNC(=O)NS(=O)(=O)C1=CC=CC=C1C(C=C1)=CC=C1CN1C2=NC=CC(C)=C2N=C1CC IDEFXINQQGAPPA-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- WUKFVNDXRWHRMJ-UHFFFAOYSA-N 2,2,2-trichloro-n-(cyclopropylmethyl)acetamide Chemical compound ClC(Cl)(Cl)C(=O)NCC1CC1 WUKFVNDXRWHRMJ-UHFFFAOYSA-N 0.000 description 1
- UPQQXPKAYZYUKO-PTQBSOBMSA-N 2,2,2-trichloroacetamide Chemical class [15NH2]C(=O)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-PTQBSOBMSA-N 0.000 description 1
- CAUOMKMOAJACPC-UHFFFAOYSA-N 2-(2-aminoethyl)-n-[2-[4-[(2-ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-yl)methyl]phenyl]phenyl]sulfonylbenzamide Chemical compound CCC1=NC2=C(C)C=C(C)N=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)C1=CC=CC=C1CCN CAUOMKMOAJACPC-UHFFFAOYSA-N 0.000 description 1
- GHCFWKFREBNSPC-UHFFFAOYSA-N 2-Amino-4-methylpyrimidine Chemical compound CC1=CC=NC(N)=N1 GHCFWKFREBNSPC-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical compound NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 description 1
- HLVIJINGDIXEEV-UHFFFAOYSA-N 2-butyl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC=C2NC(CCCC)=NC2=N1 HLVIJINGDIXEEV-UHFFFAOYSA-N 0.000 description 1
- XLXAUVCQBQMJHN-UHFFFAOYSA-N 2-butyl-3-[[4-[2-(cyclopropylmethylcarbamoylsulfamoyl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid Chemical compound CCCCC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)NCC1CC1 XLXAUVCQBQMJHN-UHFFFAOYSA-N 0.000 description 1
- OKRPJKMVQQAGQQ-UHFFFAOYSA-N 2-butyl-3-[[4-[2-(propylcarbamoylsulfamoyl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid Chemical compound CCCCC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)NCCC OKRPJKMVQQAGQQ-UHFFFAOYSA-N 0.000 description 1
- IGLWGHRTQOYFDV-UHFFFAOYSA-N 2-carbamoyl-3-nitrobenzoic acid Chemical compound NC(=O)C1=C(C(O)=O)C=CC=C1[N+]([O-])=O IGLWGHRTQOYFDV-UHFFFAOYSA-N 0.000 description 1
- HGLJRZYKFVJSEE-UHFFFAOYSA-N 2-chloro-1-(4-methylphenyl)ethanone Chemical compound CC1=CC=C(C(=O)CCl)C=C1 HGLJRZYKFVJSEE-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- IKMZGACFMXZAAT-UHFFFAOYSA-N 4-methyl-3-nitropyridin-2-amine Chemical compound CC1=CC=NC(N)=C1[N+]([O-])=O IKMZGACFMXZAAT-UHFFFAOYSA-N 0.000 description 1
- ORLGLBZRQYOWNA-UHFFFAOYSA-N 4-methylpyridin-2-amine Chemical compound CC1=CC=NC(N)=C1 ORLGLBZRQYOWNA-UHFFFAOYSA-N 0.000 description 1
- XXRKETWLPBSFFQ-UHFFFAOYSA-N 4-methylpyridine-2,3-diamine;hydrochloride Chemical compound Cl.CC1=CC=NC(N)=C1N XXRKETWLPBSFFQ-UHFFFAOYSA-N 0.000 description 1
- ROFZMKDROVBLNY-UHFFFAOYSA-N 4-nitro-2-benzofuran-1,3-dione Chemical compound [O-][N+](=O)C1=CC=CC2=C1C(=O)OC2=O ROFZMKDROVBLNY-UHFFFAOYSA-N 0.000 description 1
- HAVNKTJDVVAOOB-UHFFFAOYSA-N 6-[(2-butylimidazo[4,5-b]pyridin-3-yl)methyl]-3-chloro-1-benzothiophene-2-carboxylic acid Chemical compound C1=C2C(Cl)=C(C(O)=O)SC2=CC(CN2C3=NC=CC=C3N=C2CCCC)=C1 HAVNKTJDVVAOOB-UHFFFAOYSA-N 0.000 description 1
- YTSBZUGTKOSDKM-UHFFFAOYSA-N 7-[(2-ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-yl)methyl]-2-phenylimidazo[1,2-a]pyridine-3-carboxylic acid Chemical compound CCC1=NC2=C(C)C=C(C)N=C2N1CC(=CC1=N2)C=CN1C(C(O)=O)=C2C1=CC=CC=C1 YTSBZUGTKOSDKM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 1
- 102000004881 Angiotensinogen Human genes 0.000 description 1
- 108090001067 Angiotensinogen Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- COJOXHLOLXMZMI-UHFFFAOYSA-N CCCCC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)NC(C)C Chemical compound CCCCC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)NC(C)C COJOXHLOLXMZMI-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- GKKZMYDNDDMXSE-UHFFFAOYSA-N Ethyl 3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC=C1 GKKZMYDNDDMXSE-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229910004039 HBF4 Inorganic materials 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021137 Hypovolaemia Diseases 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 229940122344 Peptidase inhibitor Drugs 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229950011175 aminopicoline Drugs 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940127282 angiotensin receptor antagonist Drugs 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 229960003071 bacitracin Drugs 0.000 description 1
- 229930184125 bacitracin Natural products 0.000 description 1
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000005961 cardioprotection Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
- 239000003026 cod liver oil Substances 0.000 description 1
- 235000012716 cod liver oil Nutrition 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- AOQONNCNKUWWRI-UHFFFAOYSA-N cyclohexylmethyl carbonochloridate Chemical compound ClC(=O)OCC1CCCCC1 AOQONNCNKUWWRI-UHFFFAOYSA-N 0.000 description 1
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- LYOCLQBWSNCBBN-UHFFFAOYSA-N ethyl 2-bromo-3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)C(Br)C(=O)C1=CC=CC=C1 LYOCLQBWSNCBBN-UHFFFAOYSA-N 0.000 description 1
- JFDLRZBWQQGIHL-UHFFFAOYSA-N ethyl 7-(bromomethyl)-2-phenylimidazo[1,2-a]pyridine-3-carboxylate Chemical compound N1=C2C=C(CBr)C=CN2C(C(=O)OCC)=C1C1=CC=CC=C1 JFDLRZBWQQGIHL-UHFFFAOYSA-N 0.000 description 1
- MVYNOEZVTICFFL-UHFFFAOYSA-N ethyl 7-[(2-butyl-7-methoxycarbonylbenzimidazol-1-yl)methyl]-2-phenylimidazo[1,2-a]pyrimidine-3-carboxylate Chemical compound CCCCC1=NC2=CC=CC(C(=O)OC)=C2N1CC(=NC1=N2)C=CN1C(C(=O)OCC)=C2C1=CC=CC=C1 MVYNOEZVTICFFL-UHFFFAOYSA-N 0.000 description 1
- MDWARLMHRDNQBM-UHFFFAOYSA-N ethyl 7-[(2-butylimidazo[4,5-b]pyridin-3-yl)methyl]-2-phenylimidazo[1,2-a]pyrimidine-3-carboxylate Chemical compound CCCCC1=NC2=CC=CN=C2N1CC(=NC1=N2)C=CN1C(C(=O)OCC)=C2C1=CC=CC=C1 MDWARLMHRDNQBM-UHFFFAOYSA-N 0.000 description 1
- JHIKGVOBSKASJB-UHFFFAOYSA-N ethyl 7-[(2-ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-yl)methyl]-2-phenylimidazo[1,2-a]pyridine-3-carboxylate Chemical compound N1=C2C=C(CN3C4=NC(C)=CC(C)=C4N=C3CC)C=CN2C(C(=O)OCC)=C1C1=CC=CC=C1 JHIKGVOBSKASJB-UHFFFAOYSA-N 0.000 description 1
- ZFVHFQJRAAKKTD-UHFFFAOYSA-N ethyl 7-methyl-2-phenylimidazo[1,2-a]pyridine-3-carboxylate Chemical compound N1=C2C=C(C)C=CN2C(C(=O)OCC)=C1C1=CC=CC=C1 ZFVHFQJRAAKKTD-UHFFFAOYSA-N 0.000 description 1
- WUPMTTLGVVCIGB-UHFFFAOYSA-N ethyl 7-methyl-2-phenylimidazo[1,2-a]pyrimidine-3-carboxylate Chemical compound N1=C2N=C(C)C=CN2C(C(=O)OCC)=C1C1=CC=CC=C1 WUPMTTLGVVCIGB-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- XLPXOWSTBAYAOI-UHFFFAOYSA-N ethyl n-[2-[4-[(2-ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-yl)methyl]phenyl]phenyl]sulfonylcarbamate Chemical compound CCOC(=O)NS(=O)(=O)C1=CC=CC=C1C(C=C1)=CC=C1CN1C2=NC(C)=CC(C)=C2N=C1CC XLPXOWSTBAYAOI-UHFFFAOYSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000005237 imidazopyrimidines Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- MSWIFFGHKBTPMY-VFUQPONKSA-L magnesium;(e)-4-octadecoxy-4-oxobut-2-enoate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O.CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O MSWIFFGHKBTPMY-VFUQPONKSA-L 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- HDCLJQZLTMJECA-UHFFFAOYSA-N methyl 2-amino-3-nitrobenzoate Chemical compound COC(=O)C1=CC=CC([N+]([O-])=O)=C1N HDCLJQZLTMJECA-UHFFFAOYSA-N 0.000 description 1
- FLTHZFCNMVNOAM-UHFFFAOYSA-N methyl 2-butyl-3-[(3-chloro-2-methoxycarbonyl-1-benzothiophen-6-yl)methyl]benzimidazole-4-carboxylate Chemical compound C1=C2C(Cl)=C(C(=O)OC)SC2=CC(CN2C3=C(C(=O)OC)C=CC=C3N=C2CCCC)=C1 FLTHZFCNMVNOAM-UHFFFAOYSA-N 0.000 description 1
- CSTPQNFBMXFNNW-UHFFFAOYSA-N methyl 2-butyl-3-[(3-ethoxycarbonyl-2-phenylimidazo[1,2-a]pyridin-7-yl)methyl]benzimidazole-4-carboxylate Chemical compound CCCCC1=NC2=CC=CC(C(=O)OC)=C2N1CC(=CC1=N2)C=CN1C(C(=O)OCC)=C2C1=CC=CC=C1 CSTPQNFBMXFNNW-UHFFFAOYSA-N 0.000 description 1
- BFWSGMOOTANXIJ-UHFFFAOYSA-N methyl 2-butyl-3-[[4-[2-(dimethylcarbamoylsulfonylamino)phenyl]phenyl]methyl]benzimidazole-4-carboxylate Chemical compound CCCCC1=NC2=CC=CC(C(=O)OC)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1NS(=O)(=O)C(=O)N(C)C BFWSGMOOTANXIJ-UHFFFAOYSA-N 0.000 description 1
- QGCVUNBWLVLOHI-UHFFFAOYSA-N methyl 2-butyl-3-[[4-[2-(propylcarbamoylsulfamoyl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate Chemical compound CCCCC1=NC2=CC=CC(C(=O)OC)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)NCCC QGCVUNBWLVLOHI-UHFFFAOYSA-N 0.000 description 1
- XDXJAZPIRCKEPD-UHFFFAOYSA-N methyl 3-chloro-6-[(2-ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-yl)methyl]-1-benzothiophene-2-carboxylate Chemical compound C1=C2C(Cl)=C(C(=O)OC)SC2=CC(CN2C3=NC(C)=CC(C)=C3N=C2CC)=C1 XDXJAZPIRCKEPD-UHFFFAOYSA-N 0.000 description 1
- MGACFENQJJMRFI-UHFFFAOYSA-N methyl 3-chloro-6-methyl-1-benzothiophene-2-carboxylate Chemical compound CC1=CC=C2C(Cl)=C(C(=O)OC)SC2=C1 MGACFENQJJMRFI-UHFFFAOYSA-N 0.000 description 1
- VPRPZAPGAGSCAL-UHFFFAOYSA-N methyl 3-nitro-2-(pentanoylamino)benzoate Chemical compound CCCCC(=O)NC1=C(C(=O)OC)C=CC=C1[N+]([O-])=O VPRPZAPGAGSCAL-UHFFFAOYSA-N 0.000 description 1
- DHUYGWDJNCJIAJ-UHFFFAOYSA-N methyl 6-(bromomethyl)-3-chloro-1-benzothiophene-2-carboxylate Chemical compound BrCC1=CC=C2C(Cl)=C(C(=O)OC)SC2=C1 DHUYGWDJNCJIAJ-UHFFFAOYSA-N 0.000 description 1
- CPIOBMFNASQBPI-UHFFFAOYSA-N methyl 6-[(2-butylimidazo[4,5-b]pyridin-3-yl)methyl]-3-chloro-1-benzothiophene-2-carboxylate Chemical compound C1=C2C(Cl)=C(C(=O)OC)SC2=CC(CN2C3=NC=CC=C3N=C2CCCC)=C1 CPIOBMFNASQBPI-UHFFFAOYSA-N 0.000 description 1
- NZCLMHZJMDXBLO-UHFFFAOYSA-N methyl n-[2-[4-[(2-ethyl-7-methylimidazo[4,5-b]pyridin-3-yl)methyl]phenyl]phenyl]sulfonylcarbamate Chemical compound CCC1=NC2=C(C)C=CN=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(=O)OC NZCLMHZJMDXBLO-UHFFFAOYSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 210000005164 penile vein Anatomy 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000036584 pressor response Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 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
- 230000008707 rearrangement Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 210000003368 zona glomerulosa Anatomy 0.000 description 1
Classifications
-
- 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
- C07D409/06—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 only aliphatic carbon atoms
-
- 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
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Detergent Compositions (AREA)
- Lubricants (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4130659 | 1991-09-14 | ||
| DE19914131325 DE4131325A1 (de) | 1991-09-20 | 1991-09-20 | Imidazo-annellierte iso und heterocyclen, verfahren zu deren herstellung, sie enthaltende mittel und ihre verwendung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO923535D0 NO923535D0 (no) | 1992-09-11 |
| NO923535L NO923535L (no) | 1993-03-15 |
| NO300326B1 true NO300326B1 (no) | 1997-05-12 |
Family
ID=25907347
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO923535A NO300326B1 (no) | 1991-09-14 | 1992-09-11 | Imidazo-annelerte iso- og heterocykliske forbindelser og deres anvendelse |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US5444068A (sv) |
| EP (1) | EP0533058B1 (sv) |
| JP (1) | JP3459659B2 (sv) |
| KR (1) | KR930006020A (sv) |
| CN (1) | CN1070646A (sv) |
| AT (1) | ATE247644T1 (sv) |
| AU (1) | AU659485B2 (sv) |
| BR (1) | BR9203543A (sv) |
| CA (1) | CA2078058A1 (sv) |
| CZ (1) | CZ280492A3 (sv) |
| DE (1) | DE59209986D1 (sv) |
| DK (1) | DK0533058T3 (sv) |
| ES (1) | ES2204888T3 (sv) |
| FI (1) | FI924054A (sv) |
| HU (1) | HUT62892A (sv) |
| IL (1) | IL103141A0 (sv) |
| NO (1) | NO300326B1 (sv) |
| NZ (1) | NZ244303A (sv) |
| PL (1) | PL171766B1 (sv) |
| PT (1) | PT533058E (sv) |
| RU (1) | RU2076105C1 (sv) |
| TW (1) | TW300219B (sv) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5223499A (en) * | 1989-05-30 | 1993-06-29 | Merck & Co., Inc. | 6-amino substituted imidazo[4,5-bipyridines as angiotensin II antagonists |
| US5210092A (en) * | 1990-09-25 | 1993-05-11 | Fujisawa Pharmaceutical Co., Ltd. | Angiotensin ii antagonizing heterocyclic derivatives |
| CA2062558A1 (en) * | 1991-03-08 | 1992-09-09 | Prasun K. Chakravarty | Heterocyclic compounds bearing acidic functional groups as angiotensin ii antagonists |
| ATE171946T1 (de) * | 1992-07-10 | 1998-10-15 | Knoll Ag | Dioxcyclobutenderivate als angiotensin ii antagonisten |
| TW348175B (en) * | 1993-01-06 | 1998-12-21 | Hoechst Ag | Process for the preparation of biphenyl derivatives |
| CA2125251C (en) * | 1993-06-07 | 2005-04-26 | Yoshiyuki Inada | A pharmaceutical composition for angiotensin ii-mediated diseases |
| EP0628559B1 (en) * | 1993-06-10 | 2002-04-03 | Beiersdorf-Lilly GmbH | Pyrimidine compounds and their use as pharmaceuticals |
| US5571813A (en) * | 1993-06-10 | 1996-11-05 | Beiersdorf-Lilly Gmbh | Fused pyrimidine compounds and their use as pharmaceuticals |
| DE4320432A1 (de) * | 1993-06-21 | 1994-12-22 | Bayer Ag | Substituierte Mono- und Bipyridylmethylderivate |
| FR2708612B1 (fr) * | 1993-08-05 | 1996-03-01 | Roussel Uclaf | Nouveaux dérivés bicycliques de l'imidazole, leur procédé de préparation, les nouveaux intermédiaires obtenus, leur application à titre de médicaments et les compositions pharmaceutiques les renfermant. |
| EP0775134A4 (en) | 1994-08-04 | 1997-08-13 | Synaptic Pharma Corp | NEW BENZIMIDAZOLE DERIVATIVES |
| EP0849549B1 (en) * | 1996-12-18 | 2002-04-24 | Showa Denko Kabushiki Kaisha | Accumulator |
| US6495583B1 (en) | 1997-03-25 | 2002-12-17 | Synaptic Pharmaceutical Corporation | Benzimidazole derivatives |
| HRP980375A2 (en) | 1997-07-03 | 1999-04-30 | Argyrios Georgios Arvanitis | Imidazopyrimidines and imidazopyridines for the treatment of neurological disorders |
| US6365589B1 (en) | 1998-07-02 | 2002-04-02 | Bristol-Myers Squibb Pharma Company | Imidazo-pyridines, -pyridazines, and -triazines as corticotropin releasing factor antagonists |
| US6124463A (en) * | 1998-07-02 | 2000-09-26 | Dupont Pharmaceuticals | Benzimidazoles as corticotropin release factor antagonists |
| US20050267148A1 (en) * | 1998-07-15 | 2005-12-01 | Teijin Limited | Benzimidazole derivative |
| KR100903531B1 (ko) * | 1998-07-15 | 2009-06-23 | 데이진 가부시키가이샤 | 티오벤즈이미다졸 유도체 |
| EP1117966A1 (en) * | 1998-09-29 | 2001-07-25 | Stanhope Products Company | Self-positioning adsorbent package for air conditioning accumulators |
| US6279341B1 (en) * | 1999-07-01 | 2001-08-28 | Multisorb Technologies, Inc. | Self-retaining adsorbent unit |
| WO2001053272A1 (fr) * | 2000-01-17 | 2001-07-26 | Teijin Limited | Inhibiteurs de chymase humaine |
| WO2003064414A1 (en) * | 2002-01-29 | 2003-08-07 | Vicore Pharma Ab. | Tricyclic compounds useful as angiotensin ii agonists |
| AU2003263413A1 (en) * | 2002-09-17 | 2004-04-08 | Warner-Lambert Company Llc | Heterocyclic substituted piperazines for the treatment of schizophrenia |
| US20040102360A1 (en) * | 2002-10-30 | 2004-05-27 | Barnett Stanley F. | Combination therapy |
| MXPA06001669A (es) | 2003-08-12 | 2006-04-28 | 3M Innovative Properties Co | Compuestos que contienen imidazo-oxima sustituidos. |
| US7897597B2 (en) | 2003-08-27 | 2011-03-01 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted imidazoquinolines |
| WO2005023190A2 (en) | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for cd5+ b cell lymphoma |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| US8871782B2 (en) | 2003-10-03 | 2014-10-28 | 3M Innovative Properties Company | Alkoxy substituted imidazoquinolines |
| CA2545825A1 (en) | 2003-11-14 | 2005-06-02 | 3M Innovative Properties Company | Hydroxylamine substituted imidazo ring compounds |
| CA2545774A1 (en) | 2003-11-14 | 2005-06-02 | 3M Innovative Properties Company | Oxime substituted imidazo ring compounds |
| AU2004293078B2 (en) | 2003-11-25 | 2012-01-19 | 3M Innovative Properties Company | Substituted imidazo ring systems and methods |
| EP1701955A1 (en) | 2003-12-29 | 2006-09-20 | 3M Innovative Properties Company | Arylalkenyl and arylalkynyl substituted imidazoquinolines |
| CA2551399A1 (en) | 2003-12-30 | 2005-07-21 | 3M Innovative Properties Company | Imidazoquinolinyl, imidazopyridinyl, and imidazonaphthyridinyl sulfonamides |
| EP1730143A2 (en) | 2004-03-24 | 2006-12-13 | 3M Innovative Properties Company | Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines |
| WO2005123080A2 (en) | 2004-06-15 | 2005-12-29 | 3M Innovative Properties Company | Nitrogen-containing heterocyclyl substituted imidazoquinolines and imidazonaphthyridines |
| US7915281B2 (en) | 2004-06-18 | 2011-03-29 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and method |
| WO2006009826A1 (en) | 2004-06-18 | 2006-01-26 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted thiazoloquinolines and thiazolonaphthyridines |
| WO2006038923A2 (en) | 2004-06-18 | 2006-04-13 | 3M Innovative Properties Company | Aryl substituted imidazonaphthyridines |
| AU2005322898B2 (en) | 2004-12-30 | 2011-11-24 | 3M Innovative Properties Company | Chiral fused (1,2)imidazo(4,5-c) ring compounds |
| JP5313502B2 (ja) | 2004-12-30 | 2013-10-09 | スリーエム イノベイティブ プロパティズ カンパニー | 置換キラル縮合［１，２］イミダゾ［４，５−ｃ］環状化合物 |
| AU2006210392A1 (en) | 2005-02-04 | 2006-08-10 | Coley Pharmaceutical Group, Inc. | Aqueous gel formulations containing immune response modifiers |
| JP2008530113A (ja) | 2005-02-11 | 2008-08-07 | コーリー ファーマシューティカル グループ，インコーポレイテッド | オキシムおよびヒドロキシラミン置換イミダゾ［４，５−ｃ］環化合物および方法 |
| AU2006232377A1 (en) | 2005-04-01 | 2006-10-12 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridine-1,4-diamines and analogs thereof |
| WO2006107851A1 (en) | 2005-04-01 | 2006-10-12 | Coley Pharmaceutical Group, Inc. | 1-substituted pyrazolo (3,4-c) ring compounds as modulators of cytokine biosynthesis for the treatment of viral infections and neoplastic diseases |
| US7906506B2 (en) | 2006-07-12 | 2011-03-15 | 3M Innovative Properties Company | Substituted chiral fused [1,2] imidazo [4,5-c] ring compounds and methods |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| CA3089569C (en) | 2007-06-04 | 2023-12-05 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US20100120694A1 (en) | 2008-06-04 | 2010-05-13 | Synergy Pharmaceuticals, Inc. | Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders |
| EP2321341B1 (en) | 2008-07-16 | 2017-02-22 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| EP2970384A1 (en) | 2013-03-15 | 2016-01-20 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| JP2016514670A (ja) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | 他の薬物と組み合わせたグアニル酸シクラーゼ受容体アゴニスト |
| RS65632B1 (sr) | 2013-06-05 | 2024-07-31 | Bausch Health Ireland Ltd | Ultra-prečišćeni agonisti guanilat-ciklaze c, postupak njihove pripreme i upotrebe |
| JP6612874B2 (ja) | 2014-12-16 | 2019-11-27 | アクソファント サイエンシーズ ゲーエムベーハー | α７−ニコチン性アセチルコリン受容体のアゴニストとしてのジェミナル置換キヌクリジンアミド化合物 |
| MX2017016231A (es) | 2015-06-10 | 2018-11-29 | Axovant Sciences Gmbh | Compuestos de aminobencisoxazol como agonistas de receptores a7-nicotínicos de acetilcolina. |
| US10428062B2 (en) | 2015-08-12 | 2019-10-01 | Axovant Sciences Gmbh | Geminal substituted aminobenzisoxazole compounds as agonists of α7-nicotinic acetylcholine receptors |
| KR102419223B1 (ko) * | 2021-11-16 | 2022-07-08 | 세진산업(주) | 수소유기균열 방지를 위한 초고압 배관 |
| KR102643639B1 (ko) * | 2023-02-20 | 2024-03-05 | (주) 범강기연 | 무용접 가스 파이프 연결 구조 및 방법 |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4612323A (en) * | 1983-06-27 | 1986-09-16 | Sumitomo Chemical Company, Limited | Insecticidal and acaricidal derivatives of 1-benzylbenzimidazole |
| IT1173196B (it) * | 1984-02-02 | 1987-06-18 | Bellon Roger Schoum Rbs Pharma | Composti imidazopiridinici farmacologicamente attivi |
| JPS61151176A (ja) * | 1984-12-24 | 1986-07-09 | Sumitomo Chem Co Ltd | ベンズイミダゾール誘導体およびそれを有効成分とする殺虫、殺ダニ剤 |
| US4728741A (en) * | 1985-01-08 | 1988-03-01 | Smithkline Beckman Corporation | 1-substituted-2-mercapto benzimidazole compounds and intermediates |
| US4880804A (en) * | 1988-01-07 | 1989-11-14 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking benzimidazoles |
| JPH0273071A (ja) * | 1988-09-09 | 1990-03-13 | Sumitomo Chem Co Ltd | ベンズイミダゾール誘導体、その製造法およびそれを有効成分とする殺虫、殺ダニ剤 |
| GB8904174D0 (en) * | 1989-02-23 | 1989-04-05 | British Bio Technology | Compounds |
| DE3928177A1 (de) * | 1989-04-08 | 1991-02-28 | Thomae Gmbh Dr K | Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| EP0400835A1 (en) * | 1989-05-15 | 1990-12-05 | Merck & Co. Inc. | Substituted benzimidazoles as angiotensin II antagonists |
| IE64514B1 (en) * | 1989-05-23 | 1995-08-09 | Zeneca Ltd | Azaindenes |
| GB8911854D0 (en) * | 1989-05-23 | 1989-07-12 | Ici Plc | Heterocyclic compounds |
| US5102880A (en) * | 1989-05-30 | 1992-04-07 | Merck & Co., Inc. | Substituted imidazo-fused 6-membered heterocycles as angiotensin II antagonists |
| IL94390A (en) * | 1989-05-30 | 1996-03-31 | Merck & Co Inc | The 6-membered trans-nitrogen-containing heterocycles are compressed with imidazo and pharmaceutical preparations containing them |
| US5223499A (en) * | 1989-05-30 | 1993-06-29 | Merck & Co., Inc. | 6-amino substituted imidazo[4,5-bipyridines as angiotensin II antagonists |
| US5298518A (en) * | 1989-09-29 | 1994-03-29 | Eisai Co., Ltd. | Biphenylmethane derivative and pharmacological use |
| IE70593B1 (en) * | 1989-09-29 | 1996-12-11 | Eisai Co Ltd | Biphenylmethane derivative the use of it and pharmacological compositions containing same |
| IL95975A (en) * | 1989-10-24 | 1997-06-10 | Takeda Chemical Industries Ltd | N-benzyl- 2-alkylbenzimidazole derivatives, their production and pharmaceutical compositions containing them |
| GB8927277D0 (en) * | 1989-12-01 | 1990-01-31 | Glaxo Group Ltd | Chemical compounds |
| EP0430709A3 (en) * | 1989-12-01 | 1992-02-12 | Glaxo Group Limited | Benzthiophen derivatives |
| FR2658511B1 (fr) * | 1990-02-16 | 1992-06-19 | Union Pharma Scient Appl | Nouveaux derives de benzimidazole et d'azabenzimidazole, antagonistes des recepteurs au thromboxane; leurs procedes de preparation, compositions pharmaceutiques les contenant. |
| AU7820091A (en) * | 1990-06-08 | 1991-12-12 | Roussel-Uclaf | New benzimidazole derivatives, their preparation process, the new intermediates obtained, their use as medicaments and the pharmaceutical compositions containing them |
| AU653524B2 (en) * | 1990-06-08 | 1994-10-06 | Roussel-Uclaf | New imidazole derivatives, their preparation process, the new intermediates obtained, their use as medicaments and the pharmaceutical compositions containing them |
| EP0470543A1 (de) * | 1990-08-10 | 1992-02-12 | Dr. Karl Thomae GmbH | Heterocyclische Imidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zur ihrer Herstellung |
| DE4025359A1 (de) * | 1990-08-10 | 1992-02-13 | Triumph Adler Ag | Verfahren zur einstellung der abdruckenergie einer type und schreibmaschine, drucker o. dgl. zur durchfuehrung des verfahrens |
| US5087702A (en) * | 1991-01-30 | 1992-02-11 | Merck & Co., Inc. | Microbial transformation process for producing an antihypertensive product |
| US5177074A (en) * | 1991-03-26 | 1993-01-05 | Merck & Co., Inc. | Angiotensin ii antagonists incorporating a substituted thiophene or furan |
| US5158327A (en) * | 1991-10-11 | 1992-10-27 | Neil Rowe | Hydraulic hose coupling handle and method of making same |
| US5376666A (en) * | 1992-11-30 | 1994-12-27 | The Du Pont Merck Pharmaceutical Company | Angiotension-II receptor blocking, azacycloalkyl or azacycloalkenyl |
| DE4304455A1 (de) * | 1993-02-15 | 1994-08-18 | Bayer Ag | Heterocyclisch substituierte Phenyl-cyclohexan-carbonsäurederivate |
| US5395844A (en) * | 1993-06-10 | 1995-03-07 | The Du Pont Merck Pharmaceutical Company | Imidazole 5-position substituted angiotensin II antagonists |
-
1992
- 1992-03-07 TW TW081101731A patent/TW300219B/zh active
- 1992-09-10 PT PT92115500T patent/PT533058E/pt unknown
- 1992-09-10 EP EP92115500A patent/EP0533058B1/de not_active Expired - Lifetime
- 1992-09-10 DK DK92115500T patent/DK0533058T3/da active
- 1992-09-10 ES ES92115500T patent/ES2204888T3/es not_active Expired - Lifetime
- 1992-09-10 DE DE59209986T patent/DE59209986D1/de not_active Expired - Lifetime
- 1992-09-10 AT AT92115500T patent/ATE247644T1/de active
- 1992-09-10 FI FI924054A patent/FI924054A/fi not_active Application Discontinuation
- 1992-09-11 IL IL103141A patent/IL103141A0/xx unknown
- 1992-09-11 CA CA002078058A patent/CA2078058A1/en not_active Abandoned
- 1992-09-11 RU SU925053022A patent/RU2076105C1/ru active
- 1992-09-11 CZ CS922804A patent/CZ280492A3/cs unknown
- 1992-09-11 PL PL92295911A patent/PL171766B1/pl unknown
- 1992-09-11 AU AU23533/92A patent/AU659485B2/en not_active Ceased
- 1992-09-11 NZ NZ244303A patent/NZ244303A/en unknown
- 1992-09-11 BR BR929203543A patent/BR9203543A/pt not_active Application Discontinuation
- 1992-09-11 JP JP24346992A patent/JP3459659B2/ja not_active Expired - Lifetime
- 1992-09-11 NO NO923535A patent/NO300326B1/no unknown
- 1992-09-12 CN CN92110562A patent/CN1070646A/zh active Pending
- 1992-09-14 KR KR1019920016634A patent/KR930006020A/ko not_active Application Discontinuation
- 1992-09-14 HU HU9202931A patent/HUT62892A/hu unknown
-
1993
- 1993-12-13 US US08/165,655 patent/US5444068A/en not_active Expired - Lifetime
-
1995
- 1995-06-05 US US08/463,299 patent/US5635525A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH05262742A (ja) | 1993-10-12 |
| BR9203543A (pt) | 1993-04-13 |
| TW300219B (sv) | 1997-03-11 |
| US5444068A (en) | 1995-08-22 |
| JP3459659B2 (ja) | 2003-10-20 |
| CA2078058A1 (en) | 1993-03-15 |
| EP0533058B1 (de) | 2003-08-20 |
| NO923535L (no) | 1993-03-15 |
| PL295911A1 (en) | 1993-03-22 |
| PT533058E (pt) | 2004-01-30 |
| PL171766B1 (pl) | 1997-06-30 |
| ES2204888T3 (es) | 2004-05-01 |
| HU9202931D0 (en) | 1992-11-30 |
| NO923535D0 (no) | 1992-09-11 |
| CZ280492A3 (en) | 1993-04-14 |
| IL103141A0 (en) | 1993-02-21 |
| KR930006020A (ko) | 1993-04-20 |
| AU659485B2 (en) | 1995-05-18 |
| ATE247644T1 (de) | 2003-09-15 |
| FI924054A (fi) | 1993-03-15 |
| EP0533058A1 (de) | 1993-03-24 |
| RU2076105C1 (ru) | 1997-03-27 |
| CN1070646A (zh) | 1993-04-07 |
| FI924054A0 (fi) | 1992-09-10 |
| NZ244303A (en) | 1995-12-21 |
| AU2353392A (en) | 1993-03-18 |
| US5635525A (en) | 1997-06-03 |
| DK0533058T3 (da) | 2003-11-24 |
| HUT62892A (en) | 1993-06-28 |
| DE59209986D1 (de) | 2003-09-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO300326B1 (no) | Imidazo-annelerte iso- og heterocykliske forbindelser og deres anvendelse | |
| FI95254B (sv) | Förfarande för framställning av nya terapeutiskt användbara imidazol-fenyl-imidazo/1,2-a/pyridin- och imidazol-fenyl-imidazo/1,2-a/pyrimidinderivat | |
| US5604251A (en) | Imidazole derivatives with a biphenylsulfonylurea or biphenylsulfonylurethane side chain and their use as angitensin II receptors | |
| EP0503162B1 (de) | Azol-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung | |
| CZ256890A3 (en) | Substituted six-membered heterocyclic compounds with attached imidazo part as antagonists of angiotensin ii | |
| IE903815A1 (en) | Condensed imidazole derivatives and processes for¹preparation thereof | |
| EP0640084A1 (en) | 6-AMINO SUBSTITUTED IMIDAZO 4,5-b]PYRIDINES AS ANGIOTENSIN II ANTAGONISTS | |
| NO174202B (no) | Analogifremgangsm}te for fremstilling av terapeutisk aktivt azainden-derivater | |
| OA12058A (en) | 5-(2-Substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazoloÄ4,3-DÜpyrimidin-7-ones as phosphodiesterase inhibitors. | |
| NO303541B1 (no) | Substituerte bifenylpyridoner og deres anvendelse til fremstilling av legemidler | |
| CZ114593A3 (en) | Imidazopyridine derivatives, process of their preparation and pharmaceutical preparations in which they are comprised | |
| KR101468207B1 (ko) | 신규한 싸이에노[3,2-b]피리딜 우레아 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 유로텐신-Ⅱ 수용체 활성 관련 질환의 예방 또는 치료용 약학적 조성물 | |
| KR101508214B1 (ko) | 신규한 아졸-접합 피리딜 우레아 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 유로텐신-ⅱ 수용체 활성 관련 질환의 예방 또는 치료용 약학적 조성물 |