IL97426A - Pharmaceutical composition for use in reducing intraocular pressure in glaucoma containing substituted indoles and some such novel compounds - Google Patents
Pharmaceutical composition for use in reducing intraocular pressure in glaucoma containing substituted indoles and some such novel compoundsInfo
- Publication number
- IL97426A IL97426A IL9742691A IL9742691A IL97426A IL 97426 A IL97426 A IL 97426A IL 9742691 A IL9742691 A IL 9742691A IL 9742691 A IL9742691 A IL 9742691A IL 97426 A IL97426 A IL 97426A
- Authority
- IL
- Israel
- Prior art keywords
- morph
- naphthyl
- indole
- alkyl
- morpholinyl
- Prior art date
Links
- 208000010412 Glaucoma Diseases 0.000 title claims abstract description 9
- 150000001875 compounds Chemical class 0.000 title claims description 48
- 230000004410 intraocular pressure Effects 0.000 title claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 150000002475 indoles Chemical class 0.000 title description 3
- -1 lower-alkyl Chemical group 0.000 claims description 73
- 150000003839 salts Chemical class 0.000 claims description 50
- 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 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 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 13
- 239000002253 acid Substances 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 150000002431 hydrogen Chemical group 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000001725 pyrenyl group Chemical group 0.000 claims description 6
- 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 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000005605 benzo 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 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- 125000005561 phenanthryl group Chemical group 0.000 claims description 4
- 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 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000005504 styryl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- AUOUZKPZOQVDEX-UHFFFAOYSA-N 1-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-2-phenylethanone Chemical compound C12=CC=CC=C2N(CCN2CCOCC2)C(C)=C1C(=O)CC1=CC=CC=C1 AUOUZKPZOQVDEX-UHFFFAOYSA-N 0.000 claims 1
- YFKLSWYAZYPIKB-UHFFFAOYSA-N 1-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-3-naphthalen-1-ylprop-2-en-1-one Chemical compound CC1=C(C(=O)C=CC=2C3=CC=CC=C3C=CC=2)C2=CC=CC=C2N1CCN1CCOCC1 YFKLSWYAZYPIKB-UHFFFAOYSA-N 0.000 claims 1
- HBEOCIFXDAROAJ-UHFFFAOYSA-N [2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-phenanthren-9-ylmethanone Chemical compound CC1=C(C(=O)C=2C3=CC=CC=C3C3=CC=CC=C3C=2)C2=CC=CC=C2N1CCN1CCOCC1 HBEOCIFXDAROAJ-UHFFFAOYSA-N 0.000 claims 1
- IVLCIGATVZNTCI-UHFFFAOYSA-N [4-(methoxymethyl)phenyl]-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone Chemical compound C1=CC(COC)=CC=C1C(=O)C(C1=CC=CC=C11)=C(C)N1CCN1CCOCC1 IVLCIGATVZNTCI-UHFFFAOYSA-N 0.000 claims 1
- 125000004849 alkoxymethyl group Chemical group 0.000 claims 1
- FKPPZBZDWCWDGC-UHFFFAOYSA-N anthracen-1-yl-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone Chemical compound CC1=C(C(=O)C=2C3=CC4=CC=CC=C4C=C3C=CC=2)C2=CC=CC=C2N1CCN1CCOCC1 FKPPZBZDWCWDGC-UHFFFAOYSA-N 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 33
- 238000000034 method Methods 0.000 abstract description 29
- 230000001384 anti-glaucoma Effects 0.000 abstract description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 124
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 73
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- 229910000104 sodium hydride Inorganic materials 0.000 description 53
- 238000002360 preparation method Methods 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 229910000027 potassium carbonate Inorganic materials 0.000 description 37
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 33
- 239000000243 solution Substances 0.000 description 32
- 239000002585 base Substances 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 239000003921 oil Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 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
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-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
- 239000003960 organic solvent Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- 239000012312 sodium hydride Substances 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
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 239000012458 free base Substances 0.000 description 10
- 241000894007 species Species 0.000 description 10
- 238000010992 reflux Methods 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
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 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
- 230000000694 effects Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- 239000000370 acceptor Substances 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
- 238000009835 boiling Methods 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 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
- 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
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 150000001412 amines Chemical class 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
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 239000012044 organic layer Substances 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
- 238000003756 stirring Methods 0.000 description 4
- 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 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 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 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
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 3
- 108050007331 Cannabinoid receptor Proteins 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
- 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
- 239000012267 brine Substances 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 238000001816 cooling Methods 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
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 229910052757 nitrogen Inorganic materials 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
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- QZVJIIKWCINHPD-UHFFFAOYSA-N (4-methoxyphenyl)-(2-methyl-1h-indol-3-yl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C1=C(C)NC2=CC=CC=C12 QZVJIIKWCINHPD-UHFFFAOYSA-N 0.000 description 2
- JQWXKLKRPMCHSX-UHFFFAOYSA-N (5-fluoro-2-methyl-1h-indol-3-yl)-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C1=C(C)NC2=CC=C(F)C=C12 JQWXKLKRPMCHSX-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
- YNZFFALZMRAPHQ-SYYKKAFVSA-N 2-[(1r,2r,5r)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol Chemical compound OC1=CC(C(C)(C)CCCCCC)=CC=C1[C@H]1[C@H](CCCO)CC[C@@H](O)C1 YNZFFALZMRAPHQ-SYYKKAFVSA-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
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-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
- WBRNZWGLWLOWBE-UHFFFAOYSA-N [1-(2-hydroxyethyl)-2-methylindol-3-yl]-naphthalen-1-ylmethanone Chemical compound C12=CC=CC=C2N(CCO)C(C)=C1C(=O)C1=CC=CC2=CC=CC=C12 WBRNZWGLWLOWBE-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 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
- 125000002947 alkylene group Chemical group 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
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229940121376 cannabinoid receptor agonist Drugs 0.000 description 2
- 239000003537 cannabinoid receptor agonist Substances 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000012043 crude product Substances 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
- SAVROPQJUYSBDD-UHFFFAOYSA-N formyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CO SAVROPQJUYSBDD-UHFFFAOYSA-N 0.000 description 2
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- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- MEUQWHZOUDZXHH-UHFFFAOYSA-N pravadoline Chemical compound C1=CC(OC)=CC=C1C(=O)C(C1=CC=CC=C11)=C(C)N1CCN1CCOCC1 MEUQWHZOUDZXHH-UHFFFAOYSA-N 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49020190A | 1990-03-08 | 1990-03-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL97426A0 IL97426A0 (en) | 1992-06-21 |
| IL97426A true IL97426A (en) | 1996-03-31 |
Family
ID=23947024
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9742691A IL97426A (en) | 1990-03-08 | 1991-03-04 | Pharmaceutical composition for use in reducing intraocular pressure in glaucoma containing substituted indoles and some such novel compounds |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0445781B1 (es) |
| JP (1) | JP3157179B2 (es) |
| KR (1) | KR0183396B1 (es) |
| AT (1) | ATE133663T1 (es) |
| AU (1) | AU643757B2 (es) |
| CA (1) | CA2036307C (es) |
| DE (1) | DE69116705T2 (es) |
| DK (1) | DK0445781T3 (es) |
| ES (1) | ES2082872T3 (es) |
| FI (1) | FI95369C (es) |
| GR (1) | GR3019058T3 (es) |
| HU (1) | HU215125B (es) |
| IE (1) | IE72953B1 (es) |
| IL (1) | IL97426A (es) |
| MX (1) | MX174433B (es) |
| MY (1) | MY106109A (es) |
| NO (1) | NO179612C (es) |
| NZ (1) | NZ237309A (es) |
| PH (1) | PH27022A (es) |
| PT (1) | PT96938B (es) |
| RU (1) | RU2073670C1 (es) |
Families Citing this family (22)
| 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 |
| FR2713225B1 (fr) * | 1993-12-02 | 1996-03-01 | Sanofi Sa | N-pipéridino-3-pyrazolecarboxamide substitué. |
| FR2713224B1 (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. |
| NZ507391A (en) * | 1998-05-01 | 2003-12-19 | Lilly Co Eli | The compound ((3-(2-amino-1,2-dioxoethyl)-2-methyl-1- (phenylmethyl)-1H-indol-4-yl)oxy)acetic acid N-morpholino ethyl ester and its use as a sPLA 2 inhibitor |
| DK0985414T3 (da) * | 1998-05-26 | 2003-12-29 | Pfizer Prod Inc | Lægemiddel til behandling af glaukome og iskæmisk retinopati |
| AU2042301A (en) * | 1999-12-03 | 2001-06-12 | Alcon Universal Limited | 1-aminoalkyl-1H-indoles for treating glaucoma |
| DE60135972D1 (de) * | 2000-01-18 | 2008-11-13 | Merck & Co Inc | Orhthalmologische zusammenstellungen zur behandlung von ocularer hypertension |
| EP1254115A2 (en) * | 2000-02-11 | 2002-11-06 | Bristol-Myers Squibb Company | Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators for 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 |
| DE602006015309D1 (de) * | 2005-03-12 | 2010-08-19 | Unilever Nv | Haar- und/oder kopfhautpflegezusammensetzungen mit amino-oxo-indolyliden-verbindungen |
| 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 |
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 PH PH42084A patent/PH27022A/en unknown
- 1991-03-04 IL IL9742691A patent/IL97426A/en 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 NO NO910868A patent/NO179612C/no not_active IP Right Cessation
- 1991-03-05 HU HU91711A patent/HU215125B/hu unknown
- 1991-03-06 FI FI911131A patent/FI95369C/fi active
- 1991-03-06 DE DE69116705T patent/DE69116705T2/de not_active Expired - Lifetime
- 1991-03-06 AU AU72669/91A patent/AU643757B2/en not_active Expired
- 1991-03-06 ES ES91103425T patent/ES2082872T3/es not_active Expired - Lifetime
- 1991-03-06 AT AT91103425T patent/ATE133663T1/de not_active IP Right Cessation
- 1991-03-06 DK DK91103425.4T patent/DK0445781T3/da active
- 1991-03-06 EP EP91103425A patent/EP0445781B1/en not_active Expired - Lifetime
- 1991-03-07 MY MYPI91000354A patent/MY106109A/en unknown
- 1991-03-07 KR KR1019910003817A patent/KR0183396B1/ko not_active Expired - Lifetime
- 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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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| HP | Change in proprietorship | ||
| KB | Patent renewed | ||
| HP | Change in proprietorship | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| EXP | Patent expired |