PH27022A - 3-aylcarbonyl-1-aminoalkyl-1H-indole containing antiglaucoma method - Google Patents
3-aylcarbonyl-1-aminoalkyl-1H-indole containing antiglaucoma method Download PDFInfo
- Publication number
- PH27022A PH27022A PH42084A PH42084A PH27022A PH 27022 A PH27022 A PH 27022A PH 42084 A PH42084 A PH 42084A PH 42084 A PH42084 A PH 42084A PH 27022 A PH27022 A PH 27022A
- Authority
- PH
- Philippines
- Prior art keywords
- indole
- alkyl
- mole
- naphthyl
- morpholinyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 40
- 230000001384 anti-glaucoma Effects 0.000 title abstract description 6
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 4
- -1 lower-alkyl Chemical group 0.000 claims description 40
- 150000001875 compounds Chemical class 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 8
- 230000004410 intraocular pressure Effects 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 4
- 125000001725 pyrenyl group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000005561 phenanthryl group Chemical group 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000005504 styryl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 238000002360 preparation method Methods 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- 239000000243 solution Substances 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 239000000047 product Substances 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 17
- 230000000875 corresponding effect Effects 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 12
- 239000003960 organic solvent Substances 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 241000894007 species Species 0.000 description 11
- BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 description 10
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 239000012458 free base Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 239000000370 acceptor Substances 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 229930003827 cannabinoid Natural products 0.000 description 4
- 239000003557 cannabinoid Substances 0.000 description 4
- 229940065144 cannabinoids Drugs 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- XXGMIHXASFDFSM-UHFFFAOYSA-N Delta9-tetrahydrocannabinol Natural products CCCCCc1cc2OC(C)(C)C3CCC(=CC3c2c(O)c1O)C XXGMIHXASFDFSM-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 3
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 3
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229960000443 hydrochloric acid Drugs 0.000 description 3
- 235000011167 hydrochloric acid Nutrition 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
- 229910003446 platinum oxide Inorganic materials 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
- OTDPQVHIHSTMFS-UHFFFAOYSA-N (2-methyl-1h-indol-3-yl)-naphthalen-1-ylmethanone Chemical compound C1=CC=C2C(C(=O)C=3C4=CC=CC=C4NC=3C)=CC=CC2=C1 OTDPQVHIHSTMFS-UHFFFAOYSA-N 0.000 description 2
- BJUURCMGJYQCBH-UHFFFAOYSA-N (4-aminophenyl)-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone Chemical compound C12=CC=CC=C2N(CCN2CCOCC2)C(C)=C1C(=O)C1=CC=C(N)C=C1 BJUURCMGJYQCBH-UHFFFAOYSA-N 0.000 description 2
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 2
- QYAVCKAPGJSSRS-UHFFFAOYSA-N 2,7-dimethyl-1h-indole Chemical compound C1=CC(C)=C2NC(C)=CC2=C1 QYAVCKAPGJSSRS-UHFFFAOYSA-N 0.000 description 2
- ONVKWJNURJIRBF-UHFFFAOYSA-N 2-[2-methyl-3-(naphthalene-1-carbonyl)indol-1-yl]ethyl 4-methylbenzenesulfonate Chemical compound CC1=C(C(=O)C=2C3=CC=CC=C3C=CC=2)C2=CC=CC=C2N1CCOS(=O)(=O)C1=CC=C(C)C=C1 ONVKWJNURJIRBF-UHFFFAOYSA-N 0.000 description 2
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 2
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000000030 antiglaucoma agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 229940121376 cannabinoid receptor agonist Drugs 0.000 description 2
- 239000003537 cannabinoid receptor agonist Substances 0.000 description 2
- 239000000460 chlorine Chemical group 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- MEKAPBCHWBKGJR-UHFFFAOYSA-N (2,3-dihydroxyphenyl)-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone Chemical compound C12=CC=CC=C2N(CCN2CCOCC2)C(C)=C1C(=O)C1=CC=CC(O)=C1O MEKAPBCHWBKGJR-UHFFFAOYSA-N 0.000 description 1
- ANZHAPGPVHSXJZ-UHFFFAOYSA-N (2,7-dimethyl-1h-indol-3-yl)-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C1=C(C)NC2=C(C)C=CC=C12 ANZHAPGPVHSXJZ-UHFFFAOYSA-N 0.000 description 1
- PQAXTZMUDVIKCC-UHFFFAOYSA-N (3-aminophenyl)-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone Chemical compound C12=CC=CC=C2N(CCN2CCOCC2)C(C)=C1C(=O)C1=CC=CC(N)=C1 PQAXTZMUDVIKCC-UHFFFAOYSA-N 0.000 description 1
- LFCLSERTOMWFRI-UHFFFAOYSA-N (4-bromonaphthalen-1-yl)-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone Chemical compound CC1=C(C(=O)C=2C3=CC=CC=C3C(Br)=CC=2)C2=CC=CC=C2N1CCN1CCOCC1 LFCLSERTOMWFRI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US49020190A | 1990-03-08 | 1990-03-08 |
Publications (1)
Publication Number | Publication Date |
---|---|
PH27022A true PH27022A (en) | 1993-02-01 |
Family
ID=23947024
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PH42084A PH27022A (en) | 1990-03-08 | 1991-03-04 | 3-aylcarbonyl-1-aminoalkyl-1H-indole containing antiglaucoma method |
Country Status (21)
Country | Link |
---|---|
EP (1) | EP0445781B1 (fi) |
JP (1) | JP3157179B2 (fi) |
KR (1) | KR0183396B1 (fi) |
AT (1) | ATE133663T1 (fi) |
AU (1) | AU643757B2 (fi) |
CA (1) | CA2036307C (fi) |
DE (1) | DE69116705T2 (fi) |
DK (1) | DK0445781T3 (fi) |
ES (1) | ES2082872T3 (fi) |
FI (1) | FI95369C (fi) |
GR (1) | GR3019058T3 (fi) |
HU (1) | HU215125B (fi) |
IE (1) | IE72953B1 (fi) |
IL (1) | IL97426A (fi) |
MX (1) | MX174433B (fi) |
MY (1) | MY106109A (fi) |
NO (1) | NO179612C (fi) |
NZ (1) | NZ237309A (fi) |
PH (1) | PH27022A (fi) |
PT (1) | PT96938B (fi) |
RU (1) | RU2073670C1 (fi) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5068234A (en) * | 1990-02-26 | 1991-11-26 | Sterling Drug Inc. | 3-arylcarbonyl-1-(c-attached-n-heteryl)-1h-indoles |
GB9204365D0 (en) * | 1992-02-28 | 1992-04-08 | Pfizer Ltd | Indoles |
FR2692575B1 (fr) * | 1992-06-23 | 1995-06-30 | Sanofi Elf | Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
FR2713224B1 (fr) * | 1993-12-02 | 1996-03-01 | Sanofi Sa | N-pipéridino-3-pyrazolecarboxamide substitué. |
FR2713225B1 (fr) * | 1993-12-02 | 1996-03-01 | Sanofi Sa | N-pipéridino-3-pyrazolecarboxamide substitué. |
ES2099007B1 (es) * | 1993-07-16 | 1997-12-01 | Pfizer Res & Dev | Derivados de indol. |
FR2714057B1 (fr) * | 1993-12-17 | 1996-03-08 | Sanofi Elf | Nouveaux dérivés du 3-pyrazolecarboxamide, procédé pour leur préparation et compositions pharmaceutiques les contenant. |
PL344571A1 (en) * | 1998-05-01 | 2001-11-05 | Lilly Co Eli | Spla2 |
DE69910706T2 (de) * | 1998-05-26 | 2004-07-08 | Pfizer Products Inc., Groton | Medikament zur Behandlung von Glaukoma und ischämischer Retinopathie |
WO2001040183A1 (en) * | 1999-12-03 | 2001-06-07 | Alcon Universal Ltd. | 1-aminoalkyl-1h-indoles for treating glaucoma |
AU771130B2 (en) * | 2000-01-18 | 2004-03-11 | Merck & Co., Inc. | Ophthalmic compositions for treating ocular hypertension |
JP2004502642A (ja) * | 2000-02-11 | 2004-01-29 | ブリストル−マイヤーズ スクイブ カンパニー | カンナビノイドレセプターモジュレーター、それらの製造方法、および呼吸系および非呼吸系疾患の処置のためのカンナビノイドレセプターモジュレーターの使用 |
SE0203070D0 (en) * | 2002-10-16 | 2002-10-16 | Astrazeneca Ab | Novel compounds |
TW200508197A (en) | 2003-03-31 | 2005-03-01 | Ucb Sa | Indolone-acetamide derivatives, processes for preparing them and their uses |
FR2893615B1 (fr) * | 2005-11-18 | 2008-03-07 | Sanofi Aventis Sa | Derives de 3-acylindole, leur preparation et leur application en therapeutique |
KR101723125B1 (ko) | 2015-07-29 | 2017-04-04 | 이은솔 | 개선된 구조의 위생 젓가락 |
JP6025234B1 (ja) * | 2016-03-10 | 2016-11-16 | 株式会社サンライフ | 箸における箸置き形成方法及び箸置き機能を有する箸 |
CN107628981B (zh) * | 2017-10-31 | 2019-07-30 | 威海市妇女儿童医院 | 一种肉桂酰基吲哚啉化合物及其制备青光眼药物的应用 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1436771A (en) * | 1973-02-16 | 1976-05-26 | Labaz | Indole derivatives and process for preparing the same |
US4581354A (en) * | 1984-08-06 | 1986-04-08 | Sterling Drug Inc. | 3-arylcarbonyl- and 3-cycloalkylcarbonyl-1-aminoalkyl-1H-indoles, compositions and use |
US4634776A (en) * | 1984-08-06 | 1987-01-06 | Sterling Drug, Inc. | 3-arylcarbonyl-and 3-cycloalkylcarbonyl-1-aminoalkyl-1H-indoles |
US4634698A (en) * | 1984-09-24 | 1987-01-06 | Schering Corporation | Antiglaucoma agents |
DE3821148A1 (de) * | 1988-06-23 | 1989-12-28 | Erwin Von Dr Angerer | Aminoalkylindole, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate |
-
1991
- 1991-02-13 CA CA002036307A patent/CA2036307C/en not_active Expired - Lifetime
- 1991-03-01 IE IE70091A patent/IE72953B1/en not_active IP Right Cessation
- 1991-03-04 IL IL9742691A patent/IL97426A/en not_active IP Right Cessation
- 1991-03-04 PH PH42084A patent/PH27022A/en unknown
- 1991-03-05 HU HU91711A patent/HU215125B/hu unknown
- 1991-03-05 NZ NZ237309A patent/NZ237309A/xx unknown
- 1991-03-05 NO NO910868A patent/NO179612C/no not_active IP Right Cessation
- 1991-03-05 PT PT96938A patent/PT96938B/pt not_active IP Right Cessation
- 1991-03-06 FI FI911131A patent/FI95369C/fi active
- 1991-03-06 AU AU72669/91A patent/AU643757B2/en not_active Expired
- 1991-03-06 AT AT91103425T patent/ATE133663T1/de not_active IP Right Cessation
- 1991-03-06 ES ES91103425T patent/ES2082872T3/es not_active Expired - Lifetime
- 1991-03-06 EP EP91103425A patent/EP0445781B1/en not_active Expired - Lifetime
- 1991-03-06 DK DK91103425.4T patent/DK0445781T3/da active
- 1991-03-06 DE DE69116705T patent/DE69116705T2/de not_active Expired - Lifetime
- 1991-03-07 MY MYPI91000354A patent/MY106109A/en unknown
- 1991-03-07 KR KR1019910003817A patent/KR0183396B1/ko not_active IP Right Cessation
- 1991-03-08 JP JP04383191A patent/JP3157179B2/ja not_active Expired - Lifetime
- 1991-03-08 MX MX024839A patent/MX174433B/es unknown
-
1992
- 1992-05-27 RU SU925011872A patent/RU2073670C1/ru active
-
1996
- 1996-02-22 GR GR950402831T patent/GR3019058T3/el unknown
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