HU205085B - Process for producing substituted pyrrole and pyrazole derivatives and pharmaceutical compositions comprising same - Google Patents
Process for producing substituted pyrrole and pyrazole derivatives and pharmaceutical compositions comprising same Download PDFInfo
- Publication number
- HU205085B HU205085B HU8948A HU4889A HU205085B HU 205085 B HU205085 B HU 205085B HU 8948 A HU8948 A HU 8948A HU 4889 A HU4889 A HU 4889A HU 205085 B HU205085 B HU 205085B
- Authority
- HU
- Hungary
- Prior art keywords
- mmol
- compound
- methyl
- formula
- propyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 14
- 230000008569 process Effects 0.000 title claims description 11
- 239000008194 pharmaceutical composition Chemical class 0.000 title claims description 5
- 150000003233 pyrroles Chemical class 0.000 title abstract description 11
- 150000003217 pyrazoles Chemical class 0.000 title abstract description 10
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims description 124
- -1 5-tetrazolyl Chemical group 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 abstract description 4
- 206010019280 Heart failures Diseases 0.000 abstract description 4
- 229940030600 antihypertensive agent Drugs 0.000 abstract description 3
- 239000002220 antihypertensive agent Substances 0.000 abstract description 3
- 150000003852 triazoles Chemical class 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 238000005481 NMR spectroscopy Methods 0.000 description 51
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- 235000019439 ethyl acetate Nutrition 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 11
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000036772 blood pressure Effects 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 0 Cc(cc1)ccc1-c1c(*)cccc1 Chemical compound Cc(cc1)ccc1-c1c(*)cccc1 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 230000003276 anti-hypertensive effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- RMXGTMRDXKUUDJ-UHFFFAOYSA-N methyl 2-[4-(bromomethyl)phenyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1C1=CC=C(CBr)C=C1 RMXGTMRDXKUUDJ-UHFFFAOYSA-N 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- ICPWFHKNYYRBSZ-UHFFFAOYSA-M 2-methoxypropanoate Chemical compound COC(C)C([O-])=O ICPWFHKNYYRBSZ-UHFFFAOYSA-M 0.000 description 3
- ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical group OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- 108010083387 Saralasin Proteins 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000005594 diketone group Chemical group 0.000 description 3
- HTPFMOGFQKDFHX-UHFFFAOYSA-N ethyl 5-formyl-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(C=O)N1 HTPFMOGFQKDFHX-UHFFFAOYSA-N 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- PFGWGEPQIUAZME-NXSMLHPHSA-N saralasin Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)C1=CC=C(O)C=C1 PFGWGEPQIUAZME-NXSMLHPHSA-N 0.000 description 3
- 229960004785 saralasin Drugs 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- 125000006017 1-propenyl group Chemical group 0.000 description 2
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 2
- YDXGCMHMMCNTBY-UHFFFAOYSA-N 2-[4-[[5-butyl-3-(methoxymethyl)pyrazol-1-yl]methyl]phenyl]benzoic acid Chemical compound CCCCC1=CC(COC)=NN1CC1=CC=C(C=2C(=CC=CC=2)C(O)=O)C=C1 YDXGCMHMMCNTBY-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- ZTFVTXDWDFIQEU-UHFFFAOYSA-N 5-[2-[4-(bromomethyl)phenyl]phenyl]-1-trityltetrazole Chemical group C1=CC(CBr)=CC=C1C1=CC=CC=C1C1=NN=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ZTFVTXDWDFIQEU-UHFFFAOYSA-N 0.000 description 2
- BRWJNSKGKHUIHY-UHFFFAOYSA-N 5-propyl-1h-pyrrole-2-carbaldehyde Chemical compound CCCC1=CC=C(C=O)N1 BRWJNSKGKHUIHY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 108010064733 Angiotensins Proteins 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 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 2
- 241001465754 Metazoa Species 0.000 description 2
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N Minaline Natural products OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102100028255 Renin Human genes 0.000 description 2
- 108090000783 Renin Proteins 0.000 description 2
- 229920002472 Starch Chemical class 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000001913 cellulose Chemical class 0.000 description 2
- 229920002678 cellulose Chemical class 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- NZXXJLWFLINATO-UHFFFAOYSA-N ethyl 5-(1-hydroxypropyl)-1-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]pyrrole-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(C(O)CC)N1CC1=CC=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 NZXXJLWFLINATO-UHFFFAOYSA-N 0.000 description 2
- UTMUJENJZVVZLN-UHFFFAOYSA-N ethyl 5-formyl-1-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]pyrrole-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(C=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 UTMUJENJZVVZLN-UHFFFAOYSA-N 0.000 description 2
- JBHWGJMXKKDKHE-UHFFFAOYSA-N ethyl 5-prop-1-enyl-1-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]pyrrole-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(C=CC)N1CC1=CC=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 JBHWGJMXKKDKHE-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000004508 fractional distillation Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- YOMYPRTWFYKDGV-UHFFFAOYSA-N methyl 2-[4-[(5-formyl-3-propylpyrazol-1-yl)methyl]phenyl]benzoate Chemical compound N1=C(CCC)C=C(C=O)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 YOMYPRTWFYKDGV-UHFFFAOYSA-N 0.000 description 2
- JUYLPJYOGJYQHT-UHFFFAOYSA-N methyl 2-[4-[[3-butyl-5-(methoxymethyl)pyrazol-1-yl]methyl]phenyl]benzoate Chemical compound N1=C(CCCC)C=C(COC)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 JUYLPJYOGJYQHT-UHFFFAOYSA-N 0.000 description 2
- QATYKNFWLVUARK-UHFFFAOYSA-N methyl 2-[4-[[5-(methoxymethyl)-3-propylpyrazol-1-yl]methyl]phenyl]benzoate Chemical compound N1=C(CCC)C=C(COC)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 QATYKNFWLVUARK-UHFFFAOYSA-N 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
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- UCNLIORNDQWDSM-UHFFFAOYSA-N ethyl 5-butyl-1-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]pyrrole-2-carboxylate Chemical compound CCCCC1=CC=C(C(=O)OCC)N1CC1=CC=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 UCNLIORNDQWDSM-UHFFFAOYSA-N 0.000 description 1
- CNUZLCRABDUENJ-UHFFFAOYSA-N ethyl 5-butyl-1-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrrole-2-carboxylate Chemical compound CCCCC1=CC=C(C(=O)OCC)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 CNUZLCRABDUENJ-UHFFFAOYSA-N 0.000 description 1
- WYOGTPUANFUHLQ-UHFFFAOYSA-N ethyl 5-formyl-1-[[4-[2-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]phenyl]methyl]pyrrole-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(C=O)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC(C)(C)C)C=C1 WYOGTPUANFUHLQ-UHFFFAOYSA-N 0.000 description 1
- DEGYYHVSMFYQOI-UHFFFAOYSA-N ethyl 5-propyl-1-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]pyrrole-2-carboxylate Chemical compound CCCC1=CC=C(C(=O)OCC)N1CC1=CC=C(C=2C(=CC=CC=2)C=2N(N=NN=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 DEGYYHVSMFYQOI-UHFFFAOYSA-N 0.000 description 1
- AIVJJFBQHYZDEM-UHFFFAOYSA-N ethyl 5-propyl-1-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrrole-2-carboxylate Chemical compound CCCC1=CC=C(C(=O)OCC)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 AIVJJFBQHYZDEM-UHFFFAOYSA-N 0.000 description 1
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- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 1
- RQLKAKQYERUOJD-UHFFFAOYSA-N lithium;1,3,5-trimethylbenzene-6-ide Chemical compound [Li+].CC1=CC(C)=[C-]C(C)=C1 RQLKAKQYERUOJD-UHFFFAOYSA-N 0.000 description 1
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- MEFLPNNUDOJYTB-UHFFFAOYSA-N methyl 2-[4-[(3-formyl-5-propylpyrazol-1-yl)methyl]phenyl]benzoate Chemical compound CCCC1=CC(C=O)=NN1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 MEFLPNNUDOJYTB-UHFFFAOYSA-N 0.000 description 1
- GQEHJEATPMSKFP-UHFFFAOYSA-N methyl 2-[4-[[3-(hydroxymethyl)-5-propylpyrazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCC1=CC(CO)=NN1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 GQEHJEATPMSKFP-UHFFFAOYSA-N 0.000 description 1
- VCKRHHXORHRNBD-UHFFFAOYSA-N methyl 2-[4-[[3-(methoxymethyl)-5-propylpyrazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCC1=CC(COC)=NN1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 VCKRHHXORHRNBD-UHFFFAOYSA-N 0.000 description 1
- RUDWUFZTXPODLG-UHFFFAOYSA-N methyl 2-[4-[[5-(hydroxymethyl)-3-propylpyrazol-1-yl]methyl]phenyl]benzoate Chemical compound N1=C(CCC)C=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 RUDWUFZTXPODLG-UHFFFAOYSA-N 0.000 description 1
- GKXWLYQEDLTDFV-UHFFFAOYSA-N methyl 2-[4-[[5-butyl-3-(methoxymethyl)pyrazol-1-yl]methyl]phenyl]benzoate Chemical compound CCCCC1=CC(COC)=NN1CC1=CC=C(C=2C(=CC=CC=2)C(=O)OC)C=C1 GKXWLYQEDLTDFV-UHFFFAOYSA-N 0.000 description 1
- WNAFVJVEADYQAI-UHFFFAOYSA-N methyl 2-phenylbenzoate Chemical group COC(=O)C1=CC=CC=C1C1=CC=CC=C1 WNAFVJVEADYQAI-UHFFFAOYSA-N 0.000 description 1
- ZKUUVVYMPUDTGJ-UHFFFAOYSA-N methyl 5-hydroxy-4-methoxy-2-nitrobenzoate Chemical compound COC(=O)C1=CC(O)=C(OC)C=C1[N+]([O-])=O ZKUUVVYMPUDTGJ-UHFFFAOYSA-N 0.000 description 1
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- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
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- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 1
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- 206010038464 renal hypertension Diseases 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
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- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical group C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
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- 239000007909 solid dosage form Substances 0.000 description 1
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- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 229940024986 topical antifungal imidazole and triazole derivative Drugs 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
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- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
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Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur 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
-
- 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
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
-
- 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
- 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
- C07D231/14—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 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- 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
-
- 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
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
-
- 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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14166988A | 1988-01-07 | 1988-01-07 | |
US07/279,193 US5015651A (en) | 1988-01-07 | 1988-12-06 | Treatment of hypertension with 1,2,4-angiotensin II antagonists |
Publications (2)
Publication Number | Publication Date |
---|---|
HUT49571A HUT49571A (en) | 1989-10-30 |
HU205085B true HU205085B (en) | 1992-03-30 |
Family
ID=26839346
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HU8948A HU205085B (en) | 1988-01-07 | 1989-01-06 | Process for producing substituted pyrrole and pyrazole derivatives and pharmaceutical compositions comprising same |
HU906494A HU906494D0 (en) | 1988-01-07 | 1989-01-06 | Process for producing substituted 1,2,3-triazole derivatives and pharmaceutical preparatives containing these compounds |
HU9364A HU906493D0 (en) | 1988-01-07 | 1989-01-06 | Process for producing substituted 1,2,4-triazole derivatives and pharmaceutical preparatives containing these compounds |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HU906494A HU906494D0 (en) | 1988-01-07 | 1989-01-06 | Process for producing substituted 1,2,3-triazole derivatives and pharmaceutical preparatives containing these compounds |
HU9364A HU906493D0 (en) | 1988-01-07 | 1989-01-06 | Process for producing substituted 1,2,4-triazole derivatives and pharmaceutical preparatives containing these compounds |
Country Status (18)
Country | Link |
---|---|
US (1) | US5015651A (en:Method) |
EP (1) | EP0323841B1 (en:Method) |
JP (1) | JPH0725733B2 (en:Method) |
KR (1) | KR910002823B1 (en:Method) |
AT (1) | ATE92478T1 (en:Method) |
AU (1) | AU612755B2 (en:Method) |
CA (1) | CA1338013C (en:Method) |
DE (1) | DE68907921T2 (en:Method) |
DK (1) | DK171468B1 (en:Method) |
ES (1) | ES2058342T3 (en:Method) |
FI (1) | FI97381C (en:Method) |
HU (3) | HU205085B (en:Method) |
IE (1) | IE65322B1 (en:Method) |
IL (1) | IL88901A (en:Method) |
MY (1) | MY104140A (en:Method) |
NO (1) | NO174508B (en:Method) |
NZ (1) | NZ227541A (en:Method) |
PT (1) | PT89400B (en:Method) |
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1988
- 1988-12-06 US US07/279,193 patent/US5015651A/en not_active Expired - Lifetime
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1989
- 1989-01-05 CA CA000587617A patent/CA1338013C/en not_active Expired - Fee Related
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- 1989-01-05 EP EP89100142A patent/EP0323841B1/en not_active Expired - Lifetime
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- 1989-01-06 HU HU8948A patent/HU205085B/hu not_active IP Right Cessation
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- 1989-01-06 JP JP64000588A patent/JPH0725733B2/ja not_active Expired - Fee Related
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- 1989-01-06 AU AU27770/89A patent/AU612755B2/en not_active Ceased
- 1989-01-06 IL IL88901A patent/IL88901A/xx not_active IP Right Cessation
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