PH27022A - 3-aylcarbonyl-1-aminoalkyl-1H-indole containing antiglaucoma method - Google Patents

3-aylcarbonyl-1-aminoalkyl-1H-indole containing antiglaucoma method Download PDF

Info

Publication number: PH27022A
Authority: PH; Philippines
Prior art keywords: indole; alkyl; mole; naphthyl; morpholinyl
Prior art date: 1990-03-08

Application number

PH42084A

Other languages

English (en)

Inventor

Susan Jean Ward

Malcolm Rice Bell

Original Assignee

Sterling Drug Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-03-08

Filing date

1991-03-04

Publication date

1993-02-01

1991-03-04 Application filed by Sterling Drug Inc filed Critical Sterling Drug Inc

1993-02-01 Publication of PH27022A publication Critical patent/PH27022A/en

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
QIMVZMRFCMSEHB-UHFFFAOYSA-N (4-ethylphenyl)-(2-methyl-1h-indol-3-yl)methanone Chemical compound C1=CC(CC)=CC=C1C(=O)C1=C(C)NC2=CC=CC=C12 QIMVZMRFCMSEHB-UHFFFAOYSA-N 0.000 description 1
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Classifications

- 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)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Ophthalmology & Optometry (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (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)

PH42084A 1990-03-08 1991-03-04 3-aylcarbonyl-1-aminoalkyl-1H-indole containing antiglaucoma method PH27022A (en)

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 (de)
JP (1)	JP3157179B2 (de)
KR (1)	KR0183396B1 (de)
AT (1)	ATE133663T1 (de)
AU (1)	AU643757B2 (de)
CA (1)	CA2036307C (de)
DE (1)	DE69116705T2 (de)
DK (1)	DK0445781T3 (de)
ES (1)	ES2082872T3 (de)
FI (1)	FI95369C (de)
GR (1)	GR3019058T3 (de)
HU (1)	HU215125B (de)
IE (1)	IE72953B1 (de)
IL (1)	IL97426A (de)
MX (1)	MX174433B (de)
MY (1)	MY106109A (de)
NO (1)	NO179612C (de)
NZ (1)	NZ237309A (de)
PH (1)	PH27022A (de)
PT (1)	PT96938B (de)
RU (1)	RU2073670C1 (de)

Families Citing this family (22)

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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
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.
FR2692575B1 (fr) *	1992-06-23	1995-06-30	Sanofi Elf	Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant.
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
ATE247963T1 (de) *	1998-05-26	2003-09-15	Pfizer Prod Inc	Medikament zur behandlung von glaukoma und ischämischer retinopathie
AU2042301A (en) *	1999-12-03	2001-06-12	Alcon Universal Limited	1-aminoalkyl-1H-indoles for treating glaucoma
WO2001052876A1 (en) *	2000-01-18	2001-07-26	Merck & Co., Inc.	Ophthalmic compositions for treating ocular hypertension
WO2001058869A2 (en) *	2000-02-11	2001-08-16	Bristol-Myers Squibb Company	Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators in treating respiratory and non-respiratory diseases
TWI231757B (en) *	2001-09-21	2005-05-01	Solvay Pharm Bv	1H-Imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity
AR038966A1 (es) *	2002-03-18	2005-02-02	Solvay Pharm Bv	Derivados de tiazol que tienen actividad antagonista, agonista o agonista parcial de cb1
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
KR20070012389A (ko) *	2004-03-05	2007-01-25	악조 노벨 엔.브이.	칸나비노이드 ｃｂ1 수용체의 아고니스트로서의(인돌-3-일)-헤테로시클 유도체
ES2346900T3 (es) *	2005-03-12	2010-10-21	Unilever N.V.	Composiciones para el cuidado del cabello y/o el cuero cabelludo que incorporan compuestos amino-oxo-indol-ilideno.
FR2893615B1 (fr) *	2005-11-18	2008-03-07	Sanofi Aventis Sa	Derives de 3-acylindole, leur preparation et leur application en therapeutique
RU2404185C1 (ru) *	2009-04-16	2010-11-20	Учреждение Российской академии наук Институт молекулярной генетики РАН (ИМГ РАН)	РАВНОМЕРНО МЕЧЕННЫЙ ТРИТИЕМ (R)-(+)-[5-МЕТИЛ-3-(4-МОРФОЛИНИЛМЕТИЛ)-2,3-ДИГИДРО-[1,4]ОКСАЗИНО [2,3,4-hi]-6-ИНДОЛИЛ]-1-НАФТАЛИНИЛМЕТАНОН АЦЕТАТ
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

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* Cited by examiner, † Cited by third party
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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 PH PH42084A patent/PH27022A/en unknown
- 1991-03-04 IL IL9742691A patent/IL97426A/en not_active IP Right Cessation
- 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
- 1991-03-05 NZ NZ237309A patent/NZ237309A/xx unknown
- 1991-03-05 HU HU91711A patent/HU215125B/hu unknown
- 1991-03-06 DK DK91103425.4T patent/DK0445781T3/da active
- 1991-03-06 DE DE69116705T patent/DE69116705T2/de not_active Expired - Lifetime
- 1991-03-06 ES ES91103425T patent/ES2082872T3/es not_active Expired - Lifetime
- 1991-03-06 AU AU72669/91A patent/AU643757B2/en not_active Expired
- 1991-03-06 EP EP91103425A patent/EP0445781B1/de not_active Expired - Lifetime
- 1991-03-06 FI FI911131A patent/FI95369C/fi active
- 1991-03-06 AT AT91103425T patent/ATE133663T1/de not_active IP Right Cessation
- 1991-03-07 KR KR1019910003817A patent/KR0183396B1/ko not_active Expired - Lifetime
- 1991-03-07 MY MYPI91000354A patent/MY106109A/en unknown
- 1991-03-08 MX MX024839A patent/MX174433B/es unknown
- 1991-03-08 JP JP04383191A patent/JP3157179B2/ja not_active Expired - Lifetime
1992
- 1992-05-27 RU SU925011872A patent/RU2073670C1/ru active
1996
- 1996-02-22 GR GR950402831T patent/GR3019058T3/el unknown

Also Published As

Publication number	Publication date
RU2073670C1 (ru)	1997-02-20
PT96938A (pt)	1991-10-31
FI911131A0 (fi)	1991-03-06
IL97426A0 (en)	1992-06-21
NO910868L (no)	1991-09-09
CA2036307C (en)	2002-07-09
NO179612B (no)	1996-08-05
JPH04235164A (ja)	1992-08-24
MY106109A (en)	1995-03-31
IL97426A (en)	1996-03-31
EP0445781B1 (de)	1996-01-31
NO179612C (no)	1996-11-13
ATE133663T1 (de)	1996-02-15
DK0445781T3 (da)	1996-02-19
FI95369C (fi)	1996-01-25
PT96938B (pt)	1998-07-31
HU215125B (hu)	1998-09-28
IE72953B1 (en)	1997-05-07
CA2036307A1 (en)	1991-09-09
KR0183396B1 (ko)	1999-05-01
JP3157179B2 (ja)	2001-04-16
GR3019058T3 (en)	1996-05-31
MX174433B (es)	1994-05-16
NZ237309A (en)	1993-02-25
DE69116705T2 (de)	1996-09-26
IE910700A1 (en)	1991-09-11
AU7266991A (en)	1991-09-12
DE69116705D1 (de)	1996-03-14
NO910868D0 (no)	1991-03-05
FI911131L (fi)	1991-09-09
HUT56492A (en)	1991-09-30
KR910016745A (ko)	1991-11-05
ES2082872T3 (es)	1996-04-01
AU643757B2 (en)	1993-11-25
EP0445781A1 (de)	1991-09-11
FI95369B (fi)	1995-10-13
MX24839A (es)	1993-10-01

Publication	Publication Date	Title
PH27022A (en)	1993-02-01	3-aylcarbonyl-1-aminoalkyl-1H-indole containing antiglaucoma method
US4973587A (en)	1990-11-27	3-arylcarbonyl-1-aminoalkyl-1H-indole-containing antiglaucoma method
US5013837A (en)	1991-05-07	3-Arylcarbonyl-1H-indole-containing compounds
US5817651A (en)	1998-10-06	3-arylcarbonyl-1-(C-attached-N-heteryl)-1H-indoles
JP2500280B2 (ja)	1996-05-29	イミダゾ―ル、トリアゾ―ル及びテトラゾ―ル誘導体
US6936613B2 (en)	2005-08-30	Benzimidazole derivatives and pharmaceutical compositions comprising these compounds
CZ9502013A3 (en)	1996-03-13	Tricyclic 1-amino ethylpyrazole derivatives, process and intermediates for their preparation and pharmaceutical compositions based thereon
AU698580B2 (en)	1998-11-05	Serotonergic tetrahydropyridoindoles
US5563147A (en)	1996-10-08	Serotonerbic tetrahydropyridoindoles
IE851930L (en)	1986-02-06	3-carbonyl -1- aminoalkyl-1h-indoles.
US5770611A (en)	1998-06-23	Indole derivatives as 5HT1 -like agonists
US5902819A (en)	1999-05-11	Triazole derivatives
HU211967A9 (hu)	1996-01-29	3-Aril-karbonil-1H-indol-részt tartalmazó vegyületek
IL110447A (en)	1996-03-31	Substituted indoles
HU211227A9 (hu)	1995-11-28	3-Aril-karbonil-1-(C-atomhoz kapcsolódó-N-heteril)-1 H-indolok Az átmeneti oltalom az 1-23., 26-27. és 29. igénypontokra vonatkozik
HU211641A9 (hu)	1995-12-28	Az átmeneti oltalom az 1-14., 17-18. igénypontokra vonatkozik