CZ243093A3 - Benzofuran derivatives, process of their preparation and pharmaceutical preparations in which they are comprised - Google Patents
Benzofuran derivatives, process of their preparation and pharmaceutical preparations in which they are comprised Download PDFInfo
- Publication number
- CZ243093A3 CZ243093A3 CS932430A CS243093A CZ243093A3 CZ 243093 A3 CZ243093 A3 CZ 243093A3 CS 932430 A CS932430 A CS 932430A CS 243093 A CS243093 A CS 243093A CZ 243093 A3 CZ243093 A3 CZ 243093A3
- Authority
- CZ
- Czechia
- Prior art keywords
- methyl
- carbon atoms
- group
- phenyl
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 45
- 150000001907 coumarones Chemical class 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title claims description 10
- 230000008569 process Effects 0.000 title claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 177
- 150000003839 salts Chemical class 0.000 claims abstract description 46
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 30
- 150000002148 esters Chemical class 0.000 claims abstract description 28
- 239000012453 solvate Substances 0.000 claims abstract description 21
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 125000005843 halogen group Chemical group 0.000 claims abstract description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
- 238000011321 prophylaxis Methods 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 5
- 201000010099 disease Diseases 0.000 claims abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 135
- 125000004432 carbon atom Chemical group C* 0.000 claims description 110
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 107
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 101
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 100
- -1 ethoxy, cyclopropyl Chemical group 0.000 claims description 89
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 61
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 61
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 36
- 238000006243 chemical reaction Methods 0.000 claims description 30
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 25
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 19
- 239000004480 active ingredient Substances 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 13
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 11
- 102000005862 Angiotensin II Human genes 0.000 claims description 10
- 101800000733 Angiotensin-2 Proteins 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 claims description 10
- 229950006323 angiotensin ii Drugs 0.000 claims description 10
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 9
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 9
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 230000004913 activation Effects 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 230000036454 renin-angiotensin system Effects 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
- 201000006370 kidney failure Diseases 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 3
- ZBNZAJFNDPPMDT-UHFFFAOYSA-N 1h-imidazole-5-carboxamide Chemical compound NC(=O)C1=CNC=N1 ZBNZAJFNDPPMDT-UHFFFAOYSA-N 0.000 claims description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 150000001540 azides Chemical class 0.000 claims description 3
- 230000036772 blood pressure Effects 0.000 claims description 3
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 3
- 208000015114 central nervous system disease Diseases 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000012904 Bartter disease Diseases 0.000 claims description 2
- 208000010062 Bartter syndrome Diseases 0.000 claims description 2
- 208000014644 Brain disease Diseases 0.000 claims description 2
- 206010007556 Cardiac failure acute Diseases 0.000 claims description 2
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 2
- 206010058842 Cerebrovascular insufficiency Diseases 0.000 claims description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
- 206010020571 Hyperaldosteronism Diseases 0.000 claims description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 206010039710 Scleroderma Diseases 0.000 claims description 2
- 229910052770 Uranium Inorganic materials 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 150000004703 alkoxides Chemical class 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 201000002064 aortic valve insufficiency Diseases 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
- 229960003920 cocaine Drugs 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 201000009395 primary hyperaldosteronism Diseases 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 claims description 2
- 208000019553 vascular disease Diseases 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims 3
- 239000004202 carbamide Substances 0.000 claims 2
- 210000003734 kidney Anatomy 0.000 claims 2
- DNYWZCXLKNTFFI-UHFFFAOYSA-N uranium Chemical compound [U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U] DNYWZCXLKNTFFI-UHFFFAOYSA-N 0.000 claims 2
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 206010042674 Swelling Diseases 0.000 claims 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 230000036523 atherogenesis Effects 0.000 claims 1
- 229960002944 cyclofenil Drugs 0.000 claims 1
- UBKHHFOBCZFFKL-UHFFFAOYSA-N cyclopenta[c]pyran Chemical compound C1=COC=C2C=CC=C21 UBKHHFOBCZFFKL-UHFFFAOYSA-N 0.000 claims 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 230000029142 excretion Effects 0.000 claims 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
- 230000001434 glomerular Effects 0.000 claims 1
- 208000019622 heart disease Diseases 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-UHFFFAOYSA-N 0.000 claims 1
- 150000002825 nitriles Chemical group 0.000 claims 1
- 230000001681 protective effect Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 claims 1
- 230000008961 swelling Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000005289 uranyl group Chemical group 0.000 claims 1
- 230000002485 urinary effect Effects 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 abstract 2
- 208000010877 cognitive disease Diseases 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 192
- 239000000243 solution Substances 0.000 description 167
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 151
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 139
- 239000000047 product Substances 0.000 description 100
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
- 239000007787 solid Substances 0.000 description 72
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 71
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
- 239000002904 solvent Substances 0.000 description 56
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 50
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 49
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
- 235000019441 ethanol Nutrition 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
- 239000000725 suspension Substances 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 229910052757 nitrogen Inorganic materials 0.000 description 30
- 238000010992 reflux Methods 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- 239000011780 sodium chloride Substances 0.000 description 25
- 239000006260 foam Substances 0.000 description 23
- 239000000284 extract Substances 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 239000000843 powder Substances 0.000 description 15
- 239000008346 aqueous phase Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 150000002431 hydrogen Chemical class 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 description 5
- 239000004342 Benzoyl peroxide Substances 0.000 description 5
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- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 229940041476 lactose 100 mg Drugs 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000005857 malignant hypertension Diseases 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- RSIAMUSQIKRMSE-UHFFFAOYSA-N methyl 2-(5-methyl-1-benzofuran-2-yl)benzoate Chemical compound COC(=O)C1=CC=CC=C1C1=CC2=CC(C)=CC=C2O1 RSIAMUSQIKRMSE-UHFFFAOYSA-N 0.000 description 1
- SWGQITQOBPXVRC-UHFFFAOYSA-N methyl 2-bromobenzoate Chemical compound COC(=O)C1=CC=CC=C1Br SWGQITQOBPXVRC-UHFFFAOYSA-N 0.000 description 1
- IGNCVPBULCJIRO-UHFFFAOYSA-N methyl 2-fluoro-6-iodobenzoate Chemical compound COC(=O)C1=C(F)C=CC=C1I IGNCVPBULCJIRO-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- FGNGTWFJQFTFGN-UHFFFAOYSA-N n,n,n',n'-tetramethylethane-1,2-diamine Chemical compound CN(C)CCN(C)C.CN(C)CCN(C)C FGNGTWFJQFTFGN-UHFFFAOYSA-N 0.000 description 1
- DBNQIOANXZVWIP-UHFFFAOYSA-N n,n-dimethyl-1,1-bis[(2-methylpropan-2-yl)oxy]methanamine Chemical compound CC(C)(C)OC(N(C)C)OC(C)(C)C DBNQIOANXZVWIP-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- DCBSHORRWZKAKO-UHFFFAOYSA-N rac-1-monomyristoylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(O)CO DCBSHORRWZKAKO-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 208000015670 renal artery disease Diseases 0.000 description 1
- 208000015658 resistant hypertension Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 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
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- VBJGJHBYWREJQD-UHFFFAOYSA-M sodium;dihydrogen phosphate;dihydrate Chemical compound O.O.[Na+].OP(O)([O-])=O VBJGJHBYWREJQD-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940071117 starch glycolate Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 229910021515 thallium hydroxide Inorganic materials 0.000 description 1
- QGYXCSSUHCHXHB-UHFFFAOYSA-M thallium(i) hydroxide Chemical compound [OH-].[Tl+] QGYXCSSUHCHXHB-UHFFFAOYSA-M 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical group CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
- JKVRTUCVPZTEQZ-UHFFFAOYSA-N tributyltin azide Chemical compound CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-] JKVRTUCVPZTEQZ-UHFFFAOYSA-N 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- LYRCQNDYYRPFMF-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C LYRCQNDYYRPFMF-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P9/08—Vasodilators for multiple indications
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Addiction (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919110636A GB9110636D0 (en) | 1991-05-16 | 1991-05-16 | Chemical compounds |
| PCT/GB1992/000888 WO1992020674A1 (en) | 1991-05-16 | 1992-05-15 | 1h-imidazol-1-yl-methyl benzofuran derivatives, with the imidazolyl moiety being substituted by a cycloalkyl group |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ243093A3 true CZ243093A3 (en) | 1994-03-16 |
Family
ID=10695121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS932430A CZ243093A3 (en) | 1991-05-16 | 1992-05-15 | Benzofuran derivatives, process of their preparation and pharmaceutical preparations in which they are comprised |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US5332831A (enExample) |
| EP (1) | EP0514198B1 (enExample) |
| JP (1) | JPH06211846A (enExample) |
| KR (1) | KR920021541A (enExample) |
| AP (1) | AP318A (enExample) |
| AT (1) | ATE169297T1 (enExample) |
| AU (2) | AU1692692A (enExample) |
| BG (1) | BG98216A (enExample) |
| CA (1) | CA2068766A1 (enExample) |
| CZ (1) | CZ243093A3 (enExample) |
| DE (1) | DE69226472D1 (enExample) |
| FI (1) | FI935036A7 (enExample) |
| GB (1) | GB9110636D0 (enExample) |
| IL (1) | IL101882A0 (enExample) |
| IS (1) | IS1609B (enExample) |
| MX (1) | MX9202281A (enExample) |
| NO (1) | NO921944L (enExample) |
| OA (1) | OA09841A (enExample) |
| SK (1) | SK112893A3 (enExample) |
| TW (1) | TW221998B (enExample) |
| WO (1) | WO1992020674A1 (enExample) |
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| GB9218449D0 (en) | 1992-08-29 | 1992-10-14 | Boots Co Plc | Therapeutic agents |
| US5336779A (en) * | 1992-10-08 | 1994-08-09 | Nippon Gohsei Kagaku Kogyo Kabushiki Kaisha | Method of producing formylimidazoles |
| DK0853477T3 (da) * | 1995-10-06 | 2003-02-10 | Novartis Ag | AT1-receptor-antagonister til forebyggelse og behandling af postiskæmisk nyresvigt og til beskyttelse af iskæmiske nyrer |
| JP4369994B2 (ja) | 1996-02-29 | 2009-11-25 | ノバルティス アクチエンゲゼルシャフト | アポトーシスの刺激のためのａｔ▲下１▼レセプターアンタゴニスト |
| KR100567183B1 (ko) * | 1997-11-14 | 2006-06-13 | 론자 아게 | 포르밀이미다졸의제조방법 |
| US6465502B1 (en) | 1998-12-23 | 2002-10-15 | Novartis Ag | Additional therapeutic use |
| RU2271809C2 (ru) | 1998-12-23 | 2006-03-20 | Новартис Аг | Применение антагониста рецептора at-1 или модулятора рецептора ат-2 для лечения болезней, связанных с увеличением содержания рецепторов ат-1 или ат-2 |
| CN101011390A (zh) | 1999-01-26 | 2007-08-08 | 诺瓦提斯公司 | 血管紧张素ⅱ受体拮抗剂在治疗急性心肌梗塞中的应用 |
| US6211217B1 (en) | 1999-03-16 | 2001-04-03 | Novartis Ag | Method for reducing pericardial fibrosis and adhesion formation |
| DE60037192T2 (de) * | 1999-07-21 | 2008-05-15 | Takeda Pharmaceutical Co. Ltd. | Mittel zur verbesserung der erkrankungen nach zerebralen durchblutungsstörungen sowie zur verhinderung deren fortschreitens |
| SE9903028D0 (sv) | 1999-08-27 | 1999-08-27 | Astra Ab | New use |
| US6794405B2 (en) * | 2000-08-17 | 2004-09-21 | Merck & Co., Inc. | Alicyclic imidazoles as H3 agents |
| DE10335027A1 (de) | 2003-07-31 | 2005-02-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von Angiotensin II Rezeptor Antagonisten |
| ES2560247T3 (es) * | 2006-05-05 | 2016-02-18 | Dow Global Technologies Llc | Complejos de hafnio de ligandos orgánicos heterocíclicos |
| AU2007292155B2 (en) | 2006-09-05 | 2012-11-01 | Kyowa Kirin Co., Ltd. | Imidazole derivative |
| EP1908469A1 (en) | 2006-10-06 | 2008-04-09 | Boehringer Ingelheim Vetmedica Gmbh | Angiotensin II receptor antagonist for the treatment of systemic diseases in cats |
| JP5072675B2 (ja) | 2007-04-03 | 2012-11-14 | 四国化成工業株式会社 | ２−ハロイミダゾール化合物の製造方法 |
| 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 |
| CA2688161C (en) | 2007-06-04 | 2020-10-20 | Kunwar Shailubhai | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP2328910B1 (en) | 2008-06-04 | 2014-08-06 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, 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 |
| WO2014151206A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| HK1220611A1 (zh) | 2013-03-15 | 2017-05-12 | Bausch Health Ireland Limited | 用於治疗胃肠道病症的组成物 |
| CN113388007A (zh) | 2013-06-05 | 2021-09-14 | 博士医疗爱尔兰有限公司 | 鸟苷酸环化酶c的超纯激动剂、制备和使用所述激动剂的方法 |
| SI3648761T1 (sl) | 2017-07-07 | 2024-07-31 | Boehringer Ingelheim Vetmedica Gmbh | Telmisartan za profilakso ali zdravljenje hipertenzije pri mačkah |
| CN110256382A (zh) * | 2019-06-06 | 2019-09-20 | 武汉药明康德新药开发有限公司 | 一种2-(5-甲基苯并呋喃-2-基)苯甲腈的合成方法 |
| CN121175053A (zh) | 2023-05-24 | 2025-12-19 | 勃林格殷格翰动物保健有限公司 | 包含一或多种sglt-2抑制剂及替米沙坦的非人类哺乳动物中肾脏疾病和/或高血压的组合治疗和/或预防 |
| WO2025125409A1 (en) | 2023-12-15 | 2025-06-19 | Boehringer Ingelheim Vetmedica Gmbh | Angiotensin ii receptor antagonist for the prevention of systemic diseases in cats |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| GB1389827A (en) * | 1971-07-23 | 1975-04-09 | Fisons Ltd | Tetrazolyl benzopyrans |
| JPS54148788A (en) * | 1978-05-15 | 1979-11-21 | Takeda Chem Ind Ltd | 1,2-disubstituted-4-halogenoimidazole-5-acetic acid derivative and its preparation |
| US4526896A (en) * | 1978-12-26 | 1985-07-02 | Riker Laboratories, Inc. | Tetrazol-5-yl 2-nitro-3-phenylbenzofurans and antimicrobial use thereof |
| JPS5671073A (en) * | 1979-11-12 | 1981-06-13 | Takeda Chem Ind Ltd | Imidazole derivative |
| JPS5671074A (en) * | 1979-11-12 | 1981-06-13 | Takeda Chem Ind Ltd | 1,2-disubstituted-4-halogenoimidazole-5-acetic acid derivative |
| ZA824343B (en) * | 1981-07-01 | 1983-04-27 | Upjohn Co | Pyridinyl- and imidazolyl-benzofurane and benzothiophenes |
| JPS6163671A (ja) * | 1984-09-05 | 1986-04-01 | Shionogi & Co Ltd | ２，３−ジヒドロベンゾフラン−５−スルホンアミド誘導体および降圧利尿剤 |
| CA1334092C (en) * | 1986-07-11 | 1995-01-24 | David John Carini | Angiotensin ii receptor blocking imidazoles |
| US4916129A (en) * | 1989-01-19 | 1990-04-10 | E. I. Du Pont De Nemours And Company | Combination β-blocking/angiotensin II blocking antihypertensives |
| EP0403159B1 (en) * | 1989-06-14 | 2000-03-01 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids |
| WO1991000277A1 (en) * | 1989-06-30 | 1991-01-10 | E.I. Du Pont De Nemours And Company | Substituted imidazoles |
| KR950009860B1 (ko) * | 1989-06-30 | 1995-08-29 | 이. 아이. 듀퐁 드 네모아 앤드 캄파니 | 융합된 환 아릴 치환된 이미다졸과 약제학적으로 허용되는 이의 염, 이들의 제조방법 및 이들을 함유하는 약제학적 조성물 |
| JPH03204875A (ja) * | 1989-10-03 | 1991-09-06 | Wakamoto Pharmaceut Co Ltd | テトラゾール酢酸誘導体、及び該誘導体を有効成分とするアルドースレダクターゼ阻害剤 |
| CA2027937A1 (en) * | 1989-10-25 | 1991-04-26 | Richard M. Keenan | Substituted 5-¬ (tetrazolyl)alkenyl|imidazoles |
| CA2028925A1 (en) * | 1989-11-06 | 1991-05-07 | Gerald R. Girard | Substituted n-(imidazolyl)alkyl alanine derivatives |
| GB8927277D0 (en) * | 1989-12-01 | 1990-01-31 | Glaxo Group Ltd | Chemical compounds |
| US5190942A (en) * | 1991-04-22 | 1993-03-02 | E. R. Squibb & Sons, Inc. | Benzoxazole and related heterocyclic substituted imidazole and benzimidazole derivatives |
| IL101888A0 (en) * | 1991-05-16 | 1992-12-30 | Glaxo Group Ltd | Benzofuran derivatives,their preparation and pharmaceutical compositions containing them |
| DE4140519A1 (de) * | 1991-12-09 | 1993-06-17 | Merck Patent Gmbh | Benzofurane |
-
1991
- 1991-05-16 GB GB919110636A patent/GB9110636D0/en active Pending
-
1992
- 1992-05-15 NO NO92921944A patent/NO921944L/no unknown
- 1992-05-15 MX MX9202281A patent/MX9202281A/es unknown
- 1992-05-15 IL IL101882A patent/IL101882A0/xx unknown
- 1992-05-15 US US07/883,378 patent/US5332831A/en not_active Expired - Fee Related
- 1992-05-15 AP AP9200389A patent/AP318A/en active
- 1992-05-15 TW TW081103782A patent/TW221998B/zh active
- 1992-05-15 WO PCT/GB1992/000888 patent/WO1992020674A1/en not_active Ceased
- 1992-05-15 AU AU16926/92A patent/AU1692692A/en not_active Abandoned
- 1992-05-15 CA CA002068766A patent/CA2068766A1/en not_active Abandoned
- 1992-05-15 CZ CS932430A patent/CZ243093A3/cs unknown
- 1992-05-15 AU AU16321/92A patent/AU654350B2/en not_active Ceased
- 1992-05-15 DE DE69226472T patent/DE69226472D1/de not_active Expired - Lifetime
- 1992-05-15 KR KR1019920008241A patent/KR920021541A/ko not_active Ceased
- 1992-05-15 IS IS3865A patent/IS1609B/is unknown
- 1992-05-15 AT AT92304420T patent/ATE169297T1/de not_active IP Right Cessation
- 1992-05-15 EP EP92304420A patent/EP0514198B1/en not_active Expired - Lifetime
- 1992-05-15 SK SK1128-93A patent/SK112893A3/sk unknown
- 1992-05-15 JP JP4148890A patent/JPH06211846A/ja active Pending
-
1993
- 1993-10-08 OA OA60424A patent/OA09841A/en unknown
- 1993-11-12 BG BG98216A patent/BG98216A/xx unknown
- 1993-11-15 FI FI935036A patent/FI935036A7/fi not_active Application Discontinuation
-
1994
- 1994-03-31 US US08/220,698 patent/US5498722A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2068766A1 (en) | 1992-11-17 |
| EP0514198A1 (en) | 1992-11-19 |
| NO921944D0 (no) | 1992-05-15 |
| EP0514198B1 (en) | 1998-08-05 |
| US5332831A (en) | 1994-07-26 |
| TW221998B (enExample) | 1994-04-01 |
| FI935036A0 (fi) | 1993-11-15 |
| BG98216A (en) | 1994-08-15 |
| FI935036A7 (fi) | 1993-11-15 |
| NO921944L (no) | 1992-11-17 |
| GB9110636D0 (en) | 1991-07-03 |
| JPH06211846A (ja) | 1994-08-02 |
| DE69226472D1 (de) | 1998-09-10 |
| AU654350B2 (en) | 1994-11-03 |
| WO1992020674A1 (en) | 1992-11-26 |
| AP318A (en) | 1994-02-15 |
| MX9202281A (es) | 1992-11-01 |
| IL101882A0 (en) | 1992-12-30 |
| SK112893A3 (en) | 1994-11-09 |
| AU1692692A (en) | 1992-12-30 |
| ATE169297T1 (de) | 1998-08-15 |
| OA09841A (en) | 1994-08-15 |
| IS3865A (is) | 1992-11-17 |
| KR920021541A (ko) | 1992-12-18 |
| AU1632192A (en) | 1993-03-11 |
| US5498722A (en) | 1996-03-12 |
| IS1609B (is) | 1996-10-18 |
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