NO854163L - Fremgangsm¨te for fremstilling av terapeutisk aktive heter ocykliske amider. - Google Patents
Fremgangsm¨te for fremstilling av terapeutisk aktive heter ocykliske amider.Info
- Publication number
- NO854163L NO854163L NO854163A NO854163A NO854163L NO 854163 L NO854163 L NO 854163L NO 854163 A NO854163 A NO 854163A NO 854163 A NO854163 A NO 854163A NO 854163 L NO854163 L NO 854163L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- ylmethyl
- methyl
- indole
- alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 153
- 238000002360 preparation method Methods 0.000 title description 12
- 150000001408 amides Chemical class 0.000 title description 2
- 230000001225 therapeutic effect Effects 0.000 title 1
- -1 heterocyclic amides Chemical class 0.000 claims abstract description 106
- 150000001875 compounds Chemical class 0.000 claims abstract description 79
- 239000002253 acid Substances 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 15
- 229910052702 rhenium Inorganic materials 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims abstract description 5
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 244
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 123
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 123
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 55
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- 150000002148 esters Chemical class 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 23
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 21
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 10
- 239000012948 isocyanate Substances 0.000 claims description 10
- 150000002513 isocyanates Chemical class 0.000 claims description 10
- 150000003254 radicals Chemical class 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 239000002168 alkylating agent Substances 0.000 claims description 7
- 229940100198 alkylating agent Drugs 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 150000002473 indoazoles Chemical class 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 150000002540 isothiocyanates Chemical class 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
- 229920002554 vinyl polymer Polymers 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 229910052705 radium Inorganic materials 0.000 claims description 4
- 229910052701 rubidium Inorganic materials 0.000 claims description 4
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 4
- HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 claims description 3
- CHEGZJBMMKHHBL-UHFFFAOYSA-N 4-[[6-(cyclopentyloxycarbonylamino)indazol-1-yl]methyl]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1CN1C2=CC(NC(=O)OC3CCCC3)=CC=C2C=N1 CHEGZJBMMKHHBL-UHFFFAOYSA-N 0.000 claims description 3
- 239000005864 Sulphur Substances 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 150000001540 azides Chemical class 0.000 claims description 3
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 3
- 150000001768 cations Chemical class 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- PNHRAQMMHPKRGA-UHFFFAOYSA-N 4-[[3-acetyl-6-(cyclopentyloxycarbonylamino)indol-1-yl]methyl]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1CN1C2=CC(NC(=O)OC3CCCC3)=CC=C2C(C(C)=O)=C1 PNHRAQMMHPKRGA-UHFFFAOYSA-N 0.000 claims description 2
- OFGGADSGIYKUSG-UHFFFAOYSA-N 4-[[6-(2-ethylhexanoylamino)-3-(3-methoxy-3-oxoprop-1-enyl)indol-1-yl]methyl]-3-methoxybenzoic acid Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2C(C=CC(=O)OC)=CN1CC1=CC=C(C(O)=O)C=C1OC OFGGADSGIYKUSG-UHFFFAOYSA-N 0.000 claims description 2
- XJCLVUFSVBCYLV-UHFFFAOYSA-N 4-[[6-(cyclopentyloxycarbonylamino)indol-1-yl]methyl]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1CN1C2=CC(NC(=O)OC3CCCC3)=CC=C2C=C1 XJCLVUFSVBCYLV-UHFFFAOYSA-N 0.000 claims description 2
- KRKGWMRKYPWHCO-UHFFFAOYSA-N 4-[[6-[(2-cyclopentylacetyl)amino]indazol-1-yl]methyl]-3-methoxy-n-(2-methylphenyl)sulfonylbenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CN(C1=C2)N=CC1=CC=C2NC(=O)CC1CCCC1 KRKGWMRKYPWHCO-UHFFFAOYSA-N 0.000 claims description 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000005549 heteroarylene group Chemical group 0.000 claims description 2
- SKYPJUPWTDAPCO-UHFFFAOYSA-N n-(benzenesulfonyl)-3-methoxy-4-[[6-(2-phenylbutanoylamino)indazol-1-yl]methyl]benzamide Chemical compound C=1C=CC=CC=1C(CC)C(=O)NC(C=C12)=CC=C1C=NN2CC(C(=C1)OC)=CC=C1C(=O)NS(=O)(=O)C1=CC=CC=C1 SKYPJUPWTDAPCO-UHFFFAOYSA-N 0.000 claims description 2
- OLWFDFDRGRGGSY-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[3-butanoyl-6-[(2-cyclopentylacetyl)amino]indol-1-yl]methyl]-3-methoxybenzamide Chemical compound C12=CC(NC(=O)CC3CCCC3)=CC=C2C(C(=O)CCC)=CN1CC(C(=C1)OC)=CC=C1C(=O)NS(=O)(=O)C1=CC=CC=C1 OLWFDFDRGRGGSY-UHFFFAOYSA-N 0.000 claims description 2
- ONRYIYXPRLRVBM-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[6-[(2-cyclopentylacetyl)amino]indazol-1-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CN(C1=C2)N=CC1=CC=C2NC(=O)CC1CCCC1 ONRYIYXPRLRVBM-UHFFFAOYSA-N 0.000 claims description 2
- 125000000565 sulfonamide group Chemical group 0.000 claims description 2
- UXDZBJLFLOAEKD-UHFFFAOYSA-N 4-[[3-chloro-6-[(2-cyclopentylacetyl)amino]indol-1-yl]methyl]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1CN1C2=CC(NC(=O)CC3CCCC3)=CC=C2C(Cl)=C1 UXDZBJLFLOAEKD-UHFFFAOYSA-N 0.000 claims 1
- XUTIPYICPKGPSB-UHFFFAOYSA-N 4-[[6-[(2-cyclohexylacetyl)amino]indol-1-yl]methyl]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1CN1C2=CC(NC(=O)CC3CCCCC3)=CC=C2C=C1 XUTIPYICPKGPSB-UHFFFAOYSA-N 0.000 claims 1
- ZBEHEDLWMFQJDO-UHFFFAOYSA-N 4-[[6-[(2-cyclopentylacetyl)amino]indol-1-yl]methyl]-3-methoxy-n-(2-methylphenyl)sulfonylbenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CN(C1=C2)C=CC1=CC=C2NC(=O)CC1CCCC1 ZBEHEDLWMFQJDO-UHFFFAOYSA-N 0.000 claims 1
- QZUGWDCZZPNSMW-UHFFFAOYSA-N 4-[[6-[(2-cyclopentylacetyl)amino]indol-1-yl]methyl]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1CN1C2=CC(NC(=O)CC3CCCC3)=CC=C2C=C1 QZUGWDCZZPNSMW-UHFFFAOYSA-N 0.000 claims 1
- IMCBBTYAKMUOIH-UHFFFAOYSA-N cyclopentyl n-[3-acetyl-1-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]indol-6-yl]carbamate Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CN(C1=C2)C=C(C(C)=O)C1=CC=C2NC(=O)OC1CCCC1 IMCBBTYAKMUOIH-UHFFFAOYSA-N 0.000 claims 1
- AVAPSSFZKOVTJY-UHFFFAOYSA-N n-(2-aminophenyl)sulfonyl-4-[[6-[(2-cyclopentylacetyl)amino]indol-1-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)N)=CC=C1CN(C1=C2)C=CC1=CC=C2NC(=O)CC1CCCC1 AVAPSSFZKOVTJY-UHFFFAOYSA-N 0.000 claims 1
- ACVQAKRWFJEFMJ-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[3-chloro-6-[(2-cyclopentylacetyl)amino]indol-1-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CN(C1=C2)C=C(Cl)C1=CC=C2NC(=O)CC1CCCC1 ACVQAKRWFJEFMJ-UHFFFAOYSA-N 0.000 claims 1
- LWLXPXPVRJFZOI-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[6-(cyclopentanecarbonylamino)indol-1-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CN(C1=C2)C=CC1=CC=C2NC(=O)C1CCCC1 LWLXPXPVRJFZOI-UHFFFAOYSA-N 0.000 claims 1
- RJZYKCURMJALBO-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[6-[(2-cyclopentylacetyl)amino]indol-1-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CN(C1=C2)C=CC1=CC=C2NC(=O)CC1CCCC1 RJZYKCURMJALBO-UHFFFAOYSA-N 0.000 claims 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 abstract description 9
- 239000000543 intermediate Substances 0.000 abstract description 5
- 206010014824 Endotoxic shock Diseases 0.000 abstract description 4
- 206010040070 Septic Shock Diseases 0.000 abstract description 4
- 206010044541 Traumatic shock Diseases 0.000 abstract description 4
- 231100000284 endotoxic Toxicity 0.000 abstract description 4
- 230000002346 endotoxic effect Effects 0.000 abstract description 4
- 230000000172 allergic effect Effects 0.000 abstract description 3
- 208000027866 inflammatory disease Diseases 0.000 abstract description 3
- 208000026935 allergic disease Diseases 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 228
- 239000007787 solid Substances 0.000 description 192
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 129
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 114
- 239000000243 solution Substances 0.000 description 113
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 90
- 238000005481 NMR spectroscopy Methods 0.000 description 80
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 73
- 239000000203 mixture Substances 0.000 description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 238000004452 microanalysis Methods 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000003921 oil Substances 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000003480 eluent Substances 0.000 description 30
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 238000001914 filtration Methods 0.000 description 25
- 238000003818 flash chromatography Methods 0.000 description 25
- 238000010992 reflux Methods 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
- 239000012267 brine Substances 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 239000000706 filtrate Substances 0.000 description 22
- 229910000104 sodium hydride Inorganic materials 0.000 description 21
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 20
- GCSINTLJUNXLLU-UHFFFAOYSA-N methyl 3-hydroxy-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(O)=C1 GCSINTLJUNXLLU-UHFFFAOYSA-N 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 239000012312 sodium hydride Substances 0.000 description 20
- 230000007062 hydrolysis Effects 0.000 description 18
- 238000006460 hydrolysis reaction Methods 0.000 description 18
- 239000007858 starting material Substances 0.000 description 18
- 150000004702 methyl esters Chemical class 0.000 description 17
- 239000000843 powder Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 16
- 239000000284 extract Substances 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 230000029936 alkylation Effects 0.000 description 14
- 238000005804 alkylation reaction Methods 0.000 description 14
- 239000003208 petroleum Substances 0.000 description 14
- 239000000460 chlorine Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 150000002617 leukotrienes Chemical class 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 150000007513 acids Chemical class 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- ZFQCRLNKHHXELH-UHFFFAOYSA-N cyclopentyl carbonochloridate Chemical compound ClC(=O)OC1CCCC1 ZFQCRLNKHHXELH-UHFFFAOYSA-N 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
- VCTYXCBAFPDTIM-UHFFFAOYSA-N n-(1h-indol-6-yl)hexanamide Chemical compound CCCCCC(=O)NC1=CC=C2C=CNC2=C1 VCTYXCBAFPDTIM-UHFFFAOYSA-N 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 150000003536 tetrazoles Chemical class 0.000 description 9
- PSWCIARYGITEOY-UHFFFAOYSA-N 6-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2C=CNC2=C1 PSWCIARYGITEOY-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
- 230000010933 acylation Effects 0.000 description 8
- 238000005917 acylation reaction Methods 0.000 description 8
- 230000031709 bromination Effects 0.000 description 8
- 238000005893 bromination reaction Methods 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- 150000001735 carboxylic acids Chemical class 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000000354 decomposition reaction Methods 0.000 description 8
- UXSNXOMMJXTFEG-UHFFFAOYSA-N methyl 4-(bromomethyl)-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(CBr)C(OC)=C1 UXSNXOMMJXTFEG-UHFFFAOYSA-N 0.000 description 8
- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 8
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
- 239000005909 Kieselgur Substances 0.000 description 7
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000007429 general method Methods 0.000 description 7
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- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- GABQKHQNXWNJJJ-UHFFFAOYSA-N diphenylcarbamic acid Chemical compound C=1C=CC=CC=1N(C(=O)O)C1=CC=CC=C1 GABQKHQNXWNJJJ-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010952 in-situ formation Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- IENZCGNHSIMFJE-UHFFFAOYSA-N indole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=CC2=C1 IENZCGNHSIMFJE-UHFFFAOYSA-N 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229940006116 lithium hydroxide Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- QKASDIPENBEWBU-UHFFFAOYSA-N methyl 2-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1CBr QKASDIPENBEWBU-UHFFFAOYSA-N 0.000 description 1
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
- ZRAFNNDTJQYPCC-UHFFFAOYSA-N methyl 2-hydroxy-7-methyl-2,3-dihydro-1-benzofuran-4-carboxylate Chemical compound COC(=O)C1=CC=C(C)C2=C1CC(O)O2 ZRAFNNDTJQYPCC-UHFFFAOYSA-N 0.000 description 1
- WWWCQWYKUZAHLY-UHFFFAOYSA-N methyl 2-methoxy-3-methylbenzoate Chemical compound COC(=O)C1=CC=CC(C)=C1OC WWWCQWYKUZAHLY-UHFFFAOYSA-N 0.000 description 1
- LHNVKRSDQCCHEK-UHFFFAOYSA-N methyl 2-methoxy-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C=C1OC LHNVKRSDQCCHEK-UHFFFAOYSA-N 0.000 description 1
- HRIFAUHCKFFZKB-UHFFFAOYSA-N methyl 2-methoxy-5-methylbenzoate Chemical compound COC(=O)C1=CC(C)=CC=C1OC HRIFAUHCKFFZKB-UHFFFAOYSA-N 0.000 description 1
- JZARWMXGRAGBCS-UHFFFAOYSA-N methyl 3,5-dimethoxy-3-methylcyclohexa-1,5-diene-1-carboxylate Chemical compound COC(=O)C1=CC(C)(OC)CC(OC)=C1 JZARWMXGRAGBCS-UHFFFAOYSA-N 0.000 description 1
- OFNCKBSGHOIZJC-UHFFFAOYSA-N methyl 3-(bromomethyl)-2-methoxybenzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1OC OFNCKBSGHOIZJC-UHFFFAOYSA-N 0.000 description 1
- OVBBWCKBBDDWBG-UHFFFAOYSA-N methyl 3-butoxy-4-methylbenzoate Chemical compound CCCCOC1=CC(C(=O)OC)=CC=C1C OVBBWCKBBDDWBG-UHFFFAOYSA-N 0.000 description 1
- KYNVEHYJPFKPSH-UHFFFAOYSA-N methyl 3-methoxy-4-[(6-nitroindazol-1-yl)methyl]benzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC([N+]([O-])=O)=CC=C2C=N1 KYNVEHYJPFKPSH-UHFFFAOYSA-N 0.000 description 1
- JHXWKSZJGQSYCU-UHFFFAOYSA-N methyl 3-methoxy-4-[[2,3,5-trimethyl-6-(2-phenylbutanoylamino)indol-1-yl]methyl]benzoate Chemical compound C=1C=CC=CC=1C(CC)C(=O)NC(C(=CC=1C(C)=C2C)C)=CC=1N2CC1=CC=C(C(=O)OC)C=C1OC JHXWKSZJGQSYCU-UHFFFAOYSA-N 0.000 description 1
- VWVAZNYBAFTUHC-UHFFFAOYSA-N methyl 3-methoxy-4-[[5-(pentylcarbamoyl)indol-1-yl]methyl]benzoate Chemical compound C1=CC2=CC(C(=O)NCCCCC)=CC=C2N1CC1=CC=C(C(=O)OC)C=C1OC VWVAZNYBAFTUHC-UHFFFAOYSA-N 0.000 description 1
- KXDVJWDRWWASOO-UHFFFAOYSA-N methyl 3-methoxy-4-[[6-(2-phenylbutanoylamino)indazol-1-yl]methyl]benzoate Chemical compound C=1C=CC=CC=1C(CC)C(=O)NC(C=C12)=CC=C1C=NN2CC1=CC=C(C(=O)OC)C=C1OC KXDVJWDRWWASOO-UHFFFAOYSA-N 0.000 description 1
- CLRGKKWRCXQBEW-UHFFFAOYSA-N methyl 3-methoxy-4-[[6-(2-phenylbutanoylamino)indol-1-yl]methyl]benzoate Chemical compound C=1C=CC=CC=1C(CC)C(=O)NC(C=C12)=CC=C1C=CN2CC1=CC=C(C(=O)OC)C=C1OC CLRGKKWRCXQBEW-UHFFFAOYSA-N 0.000 description 1
- LLEXCSBUSVRBCA-UHFFFAOYSA-N methyl 3-methoxy-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(OC)=C1 LLEXCSBUSVRBCA-UHFFFAOYSA-N 0.000 description 1
- DCXFLSHDURQRML-UHFFFAOYSA-N methyl 4-(bromomethyl)-2-methoxybenzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1OC DCXFLSHDURQRML-UHFFFAOYSA-N 0.000 description 1
- CKOPIHBZTQSVJU-UHFFFAOYSA-N methyl 4-(bromomethyl)-3,5-dimethoxybenzoate Chemical compound COC(=O)C1=CC(OC)=C(CBr)C(OC)=C1 CKOPIHBZTQSVJU-UHFFFAOYSA-N 0.000 description 1
- XTZCVWDSGCVDFI-UHFFFAOYSA-N methyl 4-(bromomethyl)-3-chlorobenzoate Chemical compound COC(=O)C1=CC=C(CBr)C(Cl)=C1 XTZCVWDSGCVDFI-UHFFFAOYSA-N 0.000 description 1
- GPGKTIZFVDEARF-UHFFFAOYSA-N methyl 4-(hydroxymethyl)-3-methylbenzoate Chemical compound COC(=O)C1=CC=C(CO)C(C)=C1 GPGKTIZFVDEARF-UHFFFAOYSA-N 0.000 description 1
- LHOZAYRLSARWJX-UHFFFAOYSA-N methyl 4-[(3-chloro-6-nitroindazol-1-yl)methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC([N+]([O-])=O)=CC=C2C(Cl)=N1 LHOZAYRLSARWJX-UHFFFAOYSA-N 0.000 description 1
- AMNMHHQDBLZNGP-UHFFFAOYSA-N methyl 4-[(4-aminoindol-1-yl)methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC=CC(N)=C2C=C1 AMNMHHQDBLZNGP-UHFFFAOYSA-N 0.000 description 1
- WFSVQEADIJUGNF-UHFFFAOYSA-N methyl 4-[(6-amino-2,3-dihydroindol-1-yl)methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(N)=CC=C2CC1 WFSVQEADIJUGNF-UHFFFAOYSA-N 0.000 description 1
- LCESJAKMBBKRKY-UHFFFAOYSA-N methyl 4-[(6-aminoindazol-1-yl)methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1C2=CC(N)=CC=C2C=N1 LCESJAKMBBKRKY-UHFFFAOYSA-N 0.000 description 1
- HAGMMNXCYAVUPJ-UHFFFAOYSA-N methyl 4-[(6-nitroindazol-1-yl)methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1C2=CC([N+]([O-])=O)=CC=C2C=N1 HAGMMNXCYAVUPJ-UHFFFAOYSA-N 0.000 description 1
- OVDNJQUOOQFFEK-UHFFFAOYSA-N methyl 4-[1-[6-[(2-cyclopentylacetyl)amino]indol-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(C)N1C2=CC(NC(=O)CC3CCCC3)=CC=C2C=C1 OVDNJQUOOQFFEK-UHFFFAOYSA-N 0.000 description 1
- PYFZZEOZQQGVNI-UHFFFAOYSA-N methyl 4-[[3-acetyl-6-(cyclopentyloxycarbonylamino)indol-1-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)OC3CCCC3)=CC=C2C(C(C)=O)=C1 PYFZZEOZQQGVNI-UHFFFAOYSA-N 0.000 description 1
- SRLQNFHIENCMFY-UHFFFAOYSA-N methyl 4-[[3-chloro-6-[(2-cyclopentylacetyl)amino]indol-1-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)CC3CCCC3)=CC=C2C(Cl)=C1 SRLQNFHIENCMFY-UHFFFAOYSA-N 0.000 description 1
- RPKPKHPDQIVBQI-UHFFFAOYSA-N methyl 4-[[4-(hexanoylamino)indol-1-yl]methyl]-3-methoxybenzoate Chemical compound C1=CC=2C(NC(=O)CCCCC)=CC=CC=2N1CC1=CC=C(C(=O)OC)C=C1OC RPKPKHPDQIVBQI-UHFFFAOYSA-N 0.000 description 1
- QBDODOLBOGUATM-UHFFFAOYSA-N methyl 4-[[6-(2-ethylheptanoylamino)indol-1-yl]methyl]benzoate Chemical compound C12=CC(NC(=O)C(CC)CCCCC)=CC=C2C=CN1CC1=CC=C(C(=O)OC)C=C1 QBDODOLBOGUATM-UHFFFAOYSA-N 0.000 description 1
- ROBNWPUHFIAGPQ-UHFFFAOYSA-N methyl 4-[[6-(2-ethylhexanoylamino)-3-methylindol-1-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2C(C)=CN1CC1=CC=C(C(=O)OC)C=C1OC ROBNWPUHFIAGPQ-UHFFFAOYSA-N 0.000 description 1
- OATJCYAFEHVHDS-UHFFFAOYSA-N methyl 4-[[6-(2-ethylhexanoylamino)indazol-1-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2C=NN1CC1=CC=C(C(=O)OC)C=C1OC OATJCYAFEHVHDS-UHFFFAOYSA-N 0.000 description 1
- RUZVEZZKGOLGLX-UHFFFAOYSA-N methyl 4-[[6-(butoxycarbonylamino)indazol-1-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)OCCCC)=CC=C2C=NN1CC1=CC=C(C(=O)OC)C=C1OC RUZVEZZKGOLGLX-UHFFFAOYSA-N 0.000 description 1
- GXSLROXVXZRUJQ-UHFFFAOYSA-N methyl 4-[[6-(cyclopentanecarbonylamino)indol-1-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)C3CCCC3)=CC=C2C=C1 GXSLROXVXZRUJQ-UHFFFAOYSA-N 0.000 description 1
- TUJBRKRDMAJSLT-UHFFFAOYSA-N methyl 4-[[6-(cyclopentyloxycarbonylamino)indazol-1-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)OC3CCCC3)=CC=C2C=N1 TUJBRKRDMAJSLT-UHFFFAOYSA-N 0.000 description 1
- LFDIYJNPGLQZFP-UHFFFAOYSA-N methyl 4-[[6-(hexanoylamino)-2,3-dihydroindol-1-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2CCN1CC1=CC=C(C(=O)OC)C=C1OC LFDIYJNPGLQZFP-UHFFFAOYSA-N 0.000 description 1
- BYACWZFYKWWEDI-UHFFFAOYSA-N methyl 4-[[6-(hexanoylamino)-2,3-dimethylindol-1-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2C(C)=C(C)N1CC1=CC=C(C(=O)OC)C=C1OC BYACWZFYKWWEDI-UHFFFAOYSA-N 0.000 description 1
- UDHBUWFEWBSSSH-UHFFFAOYSA-N methyl 4-[[6-(hexanoylamino)indazol-1-yl]methyl]benzoate Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2C=NN1CC1=CC=C(C(=O)OC)C=C1 UDHBUWFEWBSSSH-UHFFFAOYSA-N 0.000 description 1
- GVNXIFBUAOPVJS-UHFFFAOYSA-N methyl 4-[[6-(hexanoylamino)indol-1-yl]methyl]benzoate Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2C=CN1CC1=CC=C(C(=O)OC)C=C1 GVNXIFBUAOPVJS-UHFFFAOYSA-N 0.000 description 1
- SPZGYMGJZFDCMN-UHFFFAOYSA-N methyl 4-[[6-[(2-cyclopentylacetyl)amino]-2,3-dihydroindol-1-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)CC3CCCC3)=CC=C2CC1 SPZGYMGJZFDCMN-UHFFFAOYSA-N 0.000 description 1
- OYYBUTXVSRZEGC-UHFFFAOYSA-N methyl 4-[[6-[(2-cyclopentylacetyl)amino]indazol-1-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)CC3CCCC3)=CC=C2C=N1 OYYBUTXVSRZEGC-UHFFFAOYSA-N 0.000 description 1
- KVAPUHLTFCHQFJ-UHFFFAOYSA-N methyl 4-[[6-[(2-cyclopentylacetyl)amino]indol-1-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)CC3CCCC3)=CC=C2C=C1 KVAPUHLTFCHQFJ-UHFFFAOYSA-N 0.000 description 1
- QNTSFZXGLAHYLC-UHFFFAOYSA-N methyl 4-acetylbenzoate Chemical compound COC(=O)C1=CC=C(C(C)=O)C=C1 QNTSFZXGLAHYLC-UHFFFAOYSA-N 0.000 description 1
- CYEXEOXALMJXDI-UHFFFAOYSA-N methyl 4-bromo-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1C CYEXEOXALMJXDI-UHFFFAOYSA-N 0.000 description 1
- YFPBHPCMYFCRKS-UHFFFAOYSA-N methyl 4-methyl-3-nitrobenzoate Chemical compound COC(=O)C1=CC=C(C)C([N+]([O-])=O)=C1 YFPBHPCMYFCRKS-UHFFFAOYSA-N 0.000 description 1
- ZNQXAVJDXSCHGF-UHFFFAOYSA-N methyl 5-(bromomethyl)-2-methoxybenzoate Chemical compound COC(=O)C1=CC(CBr)=CC=C1OC ZNQXAVJDXSCHGF-UHFFFAOYSA-N 0.000 description 1
- KUMSYSFZTQANSE-UHFFFAOYSA-N methyl 5-[(6-aminoindol-1-yl)methyl]furan-2-carboxylate Chemical compound O1C(C(=O)OC)=CC=C1CN1C2=CC(N)=CC=C2C=C1 KUMSYSFZTQANSE-UHFFFAOYSA-N 0.000 description 1
- UFISQQMEVCZHMH-UHFFFAOYSA-N methyl 5-[[6-(cyclopentyloxycarbonylamino)indol-1-yl]methyl]furan-2-carboxylate Chemical compound O1C(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)OC3CCCC3)=CC=C2C=C1 UFISQQMEVCZHMH-UHFFFAOYSA-N 0.000 description 1
- CKOGUHVDTMKXRR-UHFFFAOYSA-N methyl 5-[[6-(hexanoylamino)indol-1-yl]methyl]furan-2-carboxylate Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2C=CN1CC1=CC=C(C(=O)OC)O1 CKOGUHVDTMKXRR-UHFFFAOYSA-N 0.000 description 1
- GFFTZGPNJPVOQQ-UHFFFAOYSA-N methyl 7-(6-nitroindol-1-yl)heptanoate Chemical compound C1=C([N+]([O-])=O)C=C2N(CCCCCCC(=O)OC)C=CC2=C1 GFFTZGPNJPVOQQ-UHFFFAOYSA-N 0.000 description 1
- ZKGBQZKLKTXDFI-UHFFFAOYSA-N methyl 7-methyl-1-benzofuran-4-carboxylate Chemical compound COC(=O)C1=CC=C(C)C2=C1C=CO2 ZKGBQZKLKTXDFI-UHFFFAOYSA-N 0.000 description 1
- WCFAWOZRKBJWOX-UHFFFAOYSA-N methyl 8-[6-(hexanoylamino)indol-1-yl]octanoate Chemical compound CCCCCC(=O)NC1=CC=C2C=CN(CCCCCCCC(=O)OC)C2=C1 WCFAWOZRKBJWOX-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- VIJUZNJJLALGNJ-UHFFFAOYSA-N n,n-dimethylbutanamide Chemical compound CCCC(=O)N(C)C VIJUZNJJLALGNJ-UHFFFAOYSA-N 0.000 description 1
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- VCOREIPMYHNMEA-UHFFFAOYSA-N n-(benzenesulfinyl)-4-[[6-(2-ethylhexanoylamino)indol-1-yl]methyl]-3-methoxybenzamide Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2C=CN1CC(C(=C1)OC)=CC=C1C(=O)N[S+]([O-])C1=CC=CC=C1 VCOREIPMYHNMEA-UHFFFAOYSA-N 0.000 description 1
- CCUGDVLGAIBGCT-UHFFFAOYSA-N n-(benzenesulfonyl)-3-methoxy-4-[(6-nitroindol-1-yl)methyl]benzamide Chemical compound C=1C=C(CN2C3=CC(=CC=C3C=C2)[N+]([O-])=O)C(OC)=CC=1C(=O)NS(=O)(=O)C1=CC=CC=C1 CCUGDVLGAIBGCT-UHFFFAOYSA-N 0.000 description 1
- YBDIRKKZIODYSF-UHFFFAOYSA-N n-(benzenesulfonyl)-3-methoxy-4-methylbenzamide Chemical compound C1=C(C)C(OC)=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=C1 YBDIRKKZIODYSF-UHFFFAOYSA-N 0.000 description 1
- JWVPAFLUZKPGGS-UHFFFAOYSA-N n-(benzenesulfonyl)-4-(bromomethyl)-3-methoxybenzamide Chemical compound C1=C(CBr)C(OC)=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=C1 JWVPAFLUZKPGGS-UHFFFAOYSA-N 0.000 description 1
- PTJBXVAMKVKQIF-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[6-(2-ethylhexanoylamino)indol-1-yl]methyl]-2-methoxybenzamide Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2C=CN1CC(C=C1OC)=CC=C1C(=O)NS(=O)(=O)C1=CC=CC=C1 PTJBXVAMKVKQIF-UHFFFAOYSA-N 0.000 description 1
- ZJKPNRJQQAVHDZ-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[6-(2-ethylhexanoylamino)indol-1-yl]methyl]-3-methoxybenzamide Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2C=CN1CC(C(=C1)OC)=CC=C1C(=O)NS(=O)(=O)C1=CC=CC=C1 ZJKPNRJQQAVHDZ-UHFFFAOYSA-N 0.000 description 1
- OMLANZOEXMCTIH-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[6-(2-ethylhexanoylamino)indol-1-yl]methyl]benzamide Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2C=CN1CC(C=C1)=CC=C1C(=O)NS(=O)(=O)C1=CC=CC=C1 OMLANZOEXMCTIH-UHFFFAOYSA-N 0.000 description 1
- VTXJVMTUIQNBCV-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[6-[(2-cyclopentylacetyl)amino]-2,3-dihydroindol-1-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CN(C1=C2)CCC1=CC=C2NC(=O)CC1CCCC1 VTXJVMTUIQNBCV-UHFFFAOYSA-N 0.000 description 1
- GRLWLCLWHXROSI-UHFFFAOYSA-N n-(benzenesulfonyl)-7-[6-(hexanoylamino)indol-1-yl]heptanamide Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2C=CN1CCCCCCC(=O)NS(=O)(=O)C1=CC=CC=C1 GRLWLCLWHXROSI-UHFFFAOYSA-N 0.000 description 1
- UJYAZVSPFMJCLW-UHFFFAOYSA-N n-(oxomethylidene)benzenesulfonamide Chemical compound O=C=NS(=O)(=O)C1=CC=CC=C1 UJYAZVSPFMJCLW-UHFFFAOYSA-N 0.000 description 1
- HQIWSJNSRTZLQZ-UHFFFAOYSA-N n-[1-(2-bromo-1-phenylethyl)indol-6-yl]-2-phenylbutanamide Chemical compound C=1C=CC=CC=1C(CC)C(=O)NC(C=C12)=CC=C1C=CN2C(CBr)C1=CC=CC=C1 HQIWSJNSRTZLQZ-UHFFFAOYSA-N 0.000 description 1
- YZLWILXCQVBJJN-UHFFFAOYSA-N n-[1-(3-chloropropyl)indol-6-yl]hexanamide Chemical compound CCCCCC(=O)NC1=CC=C2C=CN(CCCCl)C2=C1 YZLWILXCQVBJJN-UHFFFAOYSA-N 0.000 description 1
- QMHHXVDYYAUQNJ-UHFFFAOYSA-N n-[1-(4-bromobut-2-enyl)indol-6-yl]-2-cyclopentylacetamide Chemical compound C1=C2N(CC=CCBr)C=CC2=CC=C1NC(=O)CC1CCCC1 QMHHXVDYYAUQNJ-UHFFFAOYSA-N 0.000 description 1
- LZRNIOIKWAQJMZ-UHFFFAOYSA-N n-[1-(5-bromopentyl)indol-6-yl]hexanamide Chemical compound CCCCCC(=O)NC1=CC=C2C=CN(CCCCCBr)C2=C1 LZRNIOIKWAQJMZ-UHFFFAOYSA-N 0.000 description 1
- RZFALQNWFPRYRG-UHFFFAOYSA-N n-[1-(6-cyanohexyl)indol-6-yl]-2-ethylhexanamide Chemical compound CCCCC(CC)C(=O)NC1=CC=C2C=CN(CCCCCCC#N)C2=C1 RZFALQNWFPRYRG-UHFFFAOYSA-N 0.000 description 1
- MJMRHCWPABRDFN-UHFFFAOYSA-N n-[1-(6-cyanohexyl)indol-6-yl]-2-phenylbutanamide Chemical compound C=1C=C2C=CN(CCCCCCC#N)C2=CC=1NC(=O)C(CC)C1=CC=CC=C1 MJMRHCWPABRDFN-UHFFFAOYSA-N 0.000 description 1
- MLPYMHNCMWBOOG-UHFFFAOYSA-N n-[1-(7-cyanoheptyl)indol-6-yl]hexanamide Chemical compound CCCCCC(=O)NC1=CC=C2C=CN(CCCCCCCC#N)C2=C1 MLPYMHNCMWBOOG-UHFFFAOYSA-N 0.000 description 1
- NYNZJORXKAZSMG-UHFFFAOYSA-N n-[1-(8-cyanooctyl)indol-6-yl]hexanamide Chemical compound CCCCCC(=O)NC1=CC=C2C=CN(CCCCCCCCC#N)C2=C1 NYNZJORXKAZSMG-UHFFFAOYSA-N 0.000 description 1
- USHWHZHHDWCASS-UHFFFAOYSA-N n-[1-[(3-cyanophenyl)methyl]indol-6-yl]hexanamide Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2C=CN1CC1=CC=CC(C#N)=C1 USHWHZHHDWCASS-UHFFFAOYSA-N 0.000 description 1
- MNDZYFXKECULCT-UHFFFAOYSA-N n-[1-[(4-cyano-2-methoxyphenyl)methyl]indol-6-yl]-2-cyclopentylacetamide Chemical compound COC1=CC(C#N)=CC=C1CN1C2=CC(NC(=O)CC3CCCC3)=CC=C2C=C1 MNDZYFXKECULCT-UHFFFAOYSA-N 0.000 description 1
- UQYAMFCAPZAPHJ-UHFFFAOYSA-N n-[1-[(4-cyano-2-methoxyphenyl)methyl]indol-6-yl]-2-ethylhexanamide Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2C=CN1CC1=CC=C(C#N)C=C1OC UQYAMFCAPZAPHJ-UHFFFAOYSA-N 0.000 description 1
- GLAXIYJWLLOHHB-UHFFFAOYSA-N n-[1-[(4-cyanophenyl)methyl]indol-6-yl]hexanamide Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2C=CN1CC1=CC=C(C#N)C=C1 GLAXIYJWLLOHHB-UHFFFAOYSA-N 0.000 description 1
- JQFBNJUQKXTDFT-UHFFFAOYSA-N n-[1-[3-(oxan-2-yl)propyl]indol-6-yl]hexanamide Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2C=CN1CCCC1CCCCO1 JQFBNJUQKXTDFT-UHFFFAOYSA-N 0.000 description 1
- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 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
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical class [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- CVOVQFLPEHVRFU-UHFFFAOYSA-N sodium;3-chloro-6-nitroindazol-1-ide Chemical compound [Na+].[O-][N+](=O)C1=CC=C2C(Cl)=N[N-]C2=C1 CVOVQFLPEHVRFU-UHFFFAOYSA-N 0.000 description 1
- 239000003506 spasmogen Substances 0.000 description 1
- 230000003033 spasmogenic effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- WVGJIEMQUOMWPP-UHFFFAOYSA-N tert-butyl 4-[[6-(2-ethylhexanoylamino)-3-formylindol-1-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2C(C=O)=CN1CC1=CC=C(C(=O)OC(C)(C)C)C=C1OC WVGJIEMQUOMWPP-UHFFFAOYSA-N 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 210000005092 tracheal tissue Anatomy 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000002455 vasospastic effect Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles 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 carbon atoms of the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
-
- 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
- C07D405/02—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
- C07D405/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyrrole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB848426474A GB8426474D0 (en) | 1984-10-19 | 1984-10-19 | Heterocyclic amides |
GB858507305A GB8507305D0 (en) | 1985-03-21 | 1985-03-21 | Amide derivatives |
GB858507861A GB8507861D0 (en) | 1985-03-26 | 1985-03-26 | Carboxylic acid derivatives |
GB858507862A GB8507862D0 (en) | 1985-03-26 | 1985-03-26 | Carboxamides |
Publications (1)
Publication Number | Publication Date |
---|---|
NO854163L true NO854163L (no) | 1986-04-21 |
Family
ID=27449596
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO854163A NO854163L (no) | 1984-10-19 | 1985-10-18 | Fremgangsm¨te for fremstilling av terapeutisk aktive heter ocykliske amider. |
Country Status (20)
Country | Link |
---|---|
US (1) | US4997844A (ko) |
EP (1) | EP0179619B1 (ko) |
JP (1) | JPH0745466B2 (ko) |
KR (1) | KR900007419B1 (ko) |
CN (1) | CN85108623A (ko) |
AT (1) | ATE56205T1 (ko) |
CA (1) | CA1273934A (ko) |
DE (1) | DE3579554D1 (ko) |
DK (1) | DK169541B1 (ko) |
ES (5) | ES8704458A1 (ko) |
FI (1) | FI854024L (ko) |
GB (1) | GB8524157D0 (ko) |
GR (1) | GR852519B (ko) |
HU (1) | HU194163B (ko) |
IE (1) | IE58848B1 (ko) |
IL (1) | IL76756A (ko) |
NO (1) | NO854163L (ko) |
NZ (1) | NZ213872A (ko) |
PT (1) | PT81297B (ko) |
ZW (1) | ZW18185A1 (ko) |
Families Citing this family (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4837235A (en) * | 1985-10-17 | 1989-06-06 | Ici Americas Inc. | Indole and indazole keto sulphones as leukotriene antagonists |
GB8623429D0 (en) * | 1985-10-17 | 1986-11-05 | Ici America Inc | Carboximide derivatives |
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1985
- 1985-10-01 GB GB858524157A patent/GB8524157D0/en active Pending
- 1985-10-14 PT PT81297A patent/PT81297B/pt not_active IP Right Cessation
- 1985-10-16 FI FI854024A patent/FI854024L/fi not_active Application Discontinuation
- 1985-10-16 HU HU854007A patent/HU194163B/hu not_active IP Right Cessation
- 1985-10-17 NZ NZ213872A patent/NZ213872A/xx unknown
- 1985-10-17 DE DE8585307498T patent/DE3579554D1/de not_active Expired - Fee Related
- 1985-10-17 EP EP85307498A patent/EP0179619B1/en not_active Expired - Lifetime
- 1985-10-17 ZW ZW181/85A patent/ZW18185A1/xx unknown
- 1985-10-17 AT AT85307498T patent/ATE56205T1/de not_active IP Right Cessation
- 1985-10-18 NO NO854163A patent/NO854163L/no unknown
- 1985-10-18 US US06/788,807 patent/US4997844A/en not_active Expired - Lifetime
- 1985-10-18 JP JP60231457A patent/JPH0745466B2/ja not_active Expired - Fee Related
- 1985-10-18 ES ES548011A patent/ES8704458A1/es not_active Expired
- 1985-10-18 GR GR852519A patent/GR852519B/el unknown
- 1985-10-18 IL IL76756A patent/IL76756A/xx not_active IP Right Cessation
- 1985-10-18 CA CA000493372A patent/CA1273934A/en not_active Expired - Lifetime
- 1985-10-18 DK DK479385A patent/DK169541B1/da not_active IP Right Cessation
- 1985-10-18 IE IE258985A patent/IE58848B1/en not_active IP Right Cessation
- 1985-10-19 CN CN198585108623A patent/CN85108623A/zh active Pending
- 1985-10-19 KR KR1019850007730A patent/KR900007419B1/ko not_active IP Right Cessation
-
1986
- 1986-04-30 ES ES554579A patent/ES8802495A1/es not_active Expired
- 1986-04-30 ES ES554580A patent/ES8801786A1/es not_active Expired
- 1986-04-30 ES ES554577A patent/ES8800899A1/es not_active Expired
- 1986-04-30 ES ES554578A patent/ES8800900A1/es not_active Expired
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