PL72358B1 - - Google Patents
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- PL72358B1 PL72358B1 PL1971151699A PL15169971A PL72358B1 PL 72358 B1 PL72358 B1 PL 72358B1 PL 1971151699 A PL1971151699 A PL 1971151699A PL 15169971 A PL15169971 A PL 15169971A PL 72358 B1 PL72358 B1 PL 72358B1
- Authority
- PL
- Poland
- Prior art keywords
- group
- benzodiazepine
- formula
- compound
- phenyl
- Prior art date
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- -1 di-substituted amino group Chemical group 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 37
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 150000007522 mineralic acids Chemical class 0.000 claims description 8
- 150000007524 organic acids Chemical class 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 229940049706 benzodiazepine Drugs 0.000 claims description 5
- 125000002576 diazepinyl group Chemical class N1N=C(C=CC=C1)* 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 235000005985 organic acids Nutrition 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000007017 scission Effects 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical group SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims 3
- AXVUIZWKRNOPMP-UHFFFAOYSA-N C1(=CC=CC=C1)C1=NC2=C(C=NC1)C=C(C=C2)Cl Chemical compound C1(=CC=CC=C1)C1=NC2=C(C=NC1)C=C(C=C2)Cl AXVUIZWKRNOPMP-UHFFFAOYSA-N 0.000 claims 1
- 125000004423 acyloxy group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 30
- 239000003208 petroleum Substances 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 230000035484 reaction time Effects 0.000 description 11
- 239000000203 mixture Substances 0.000 description 10
- WXILCXHXMMBIHC-UHFFFAOYSA-N 1,4-benzodiazepin-1-ylmethanol Chemical compound OCN1C=CN=CC2=CC=CC=C12 WXILCXHXMMBIHC-UHFFFAOYSA-N 0.000 description 9
- YOHJKBKLWJAEHF-UHFFFAOYSA-N 7-chloro-2-methylsulfanyl-5-phenyl-3h-1,4-benzodiazepine Chemical compound N=1CC(SC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 YOHJKBKLWJAEHF-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- ZURUZYHEEMDQBU-UHFFFAOYSA-N alpha-Hydroxyalprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(CO)=NN=C2CN=C1C1=CC=CC=C1 ZURUZYHEEMDQBU-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 7
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- WTGRHCXBHHGMEC-UHFFFAOYSA-N 2-methylsulfanyl-5-phenyl-3h-1,4-benzodiazepine Chemical compound N=1CC(SC)=NC2=CC=CC=C2C=1C1=CC=CC=C1 WTGRHCXBHHGMEC-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 4
- 229920001592 potato starch Polymers 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- DRTXHTRRQCBKGA-UHFFFAOYSA-N 1,2-benzodiazepin-1-ylmethanol Chemical compound OCN1N=CC=CC2=CC=CC=C12 DRTXHTRRQCBKGA-UHFFFAOYSA-N 0.000 description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 3
- KYGYCAUNXCVLQM-UHFFFAOYSA-N 2-phenylmethoxyacetohydrazide Chemical compound NNC(=O)COCC1=CC=CC=C1 KYGYCAUNXCVLQM-UHFFFAOYSA-N 0.000 description 3
- QQMKUVODFFHQTG-UHFFFAOYSA-N 3-phenylmethoxypropanehydrazide Chemical compound NNC(=O)CCOCC1=CC=CC=C1 QQMKUVODFFHQTG-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 2
- NMNHXPQJISZDMF-UHFFFAOYSA-N 3-ethoxypropanehydrazide Chemical compound CCOCCC(=O)NN NMNHXPQJISZDMF-UHFFFAOYSA-N 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- HFPOKTLTQQGYOD-UHFFFAOYSA-N 8-bromo-1-[(4-methoxyphenyl)methoxymethyl]-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C1=CC(OC)=CC=C1COCC1=NN=C2N1C1=CC=C(Br)C=C1C(C=1C=CC=CC=1)=NC2 HFPOKTLTQQGYOD-UHFFFAOYSA-N 0.000 description 2
- CNXMBTJLZMMNHE-UHFFFAOYSA-N 8-chloro-6-phenyl-1-(phenylmethoxymethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(Cl)=CC=C(N23)C=1C(C=1C=CC=CC=1)=NCC3=NN=C2COCC1=CC=CC=C1 CNXMBTJLZMMNHE-UHFFFAOYSA-N 0.000 description 2
- SNWNVCIFXJVISJ-UHFFFAOYSA-N 8-methoxy-6-phenyl-1-(phenylmethoxymethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(OC)=CC=C(N23)C=1C(C=1C=CC=CC=1)=NCC3=NN=C2COCC1=CC=CC=C1 SNWNVCIFXJVISJ-UHFFFAOYSA-N 0.000 description 2
- QXPJAGSZISCXQG-UHFFFAOYSA-N 8-methyl-6-phenyl-1-(phenylmethoxymethyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(C)=CC=C(N23)C=1C(C=1C=CC=CC=1)=NCC3=NN=C2COCC1=CC=CC=C1 QXPJAGSZISCXQG-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- BHUYWUDMVCLHND-UHFFFAOYSA-N alpha-Hydroxytriazolam Chemical compound C12=CC(Cl)=CC=C2N2C(CO)=NN=C2CN=C1C1=CC=CC=C1Cl BHUYWUDMVCLHND-UHFFFAOYSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- KJASTBCNGFYKSR-UHFFFAOYSA-N prop-2-enehydrazide Chemical class NNC(=O)C=C KJASTBCNGFYKSR-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000002966 varnish Substances 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- DFOBVHAGIRZQIO-UHFFFAOYSA-N (6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)methanol Chemical compound C12=CC=CC=C2N2C(CO)=NN=C2CN=C1C1=CC=CC=C1 DFOBVHAGIRZQIO-UHFFFAOYSA-N 0.000 description 1
- KRINWUOUZICPBX-UHFFFAOYSA-N (8-methoxy-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)methanol Chemical compound C=1C(OC)=CC=C(N2C(CO)=NN=C2CN=2)C=1C=2C1=CC=CC=C1 KRINWUOUZICPBX-UHFFFAOYSA-N 0.000 description 1
- KNUCJCRVSUJPRV-UHFFFAOYSA-N (8-methyl-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)methanol Chemical compound C=1C(C)=CC=C(N2C(CO)=NN=C2CN=2)C=1C=2C1=CC=CC=C1 KNUCJCRVSUJPRV-UHFFFAOYSA-N 0.000 description 1
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OGGPXWWYSTTYQD-UHFFFAOYSA-N 1-(8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)propan-2-ol Chemical compound C12=CC(Cl)=CC=C2N2C(CC(O)C)=NN=C2CN=C1C1=CC=CC=C1 OGGPXWWYSTTYQD-UHFFFAOYSA-N 0.000 description 1
- NVVBOHPQSSQVKO-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methoxymethyl]-8-methyl-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C1=CC(OC)=CC=C1COCC1=NN=C2N1C1=CC=C(C)C=C1C(C=1C=CC=CC=1)=NC2 NVVBOHPQSSQVKO-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 1
- OLCPBZOIQKLYOU-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methoxy]acetohydrazide Chemical compound COC1=CC=C(COCC(=O)NN)C=C1 OLCPBZOIQKLYOU-UHFFFAOYSA-N 0.000 description 1
- LNJHYWAAVRVKIC-UHFFFAOYSA-N 2-benzhydryloxyacetohydrazide Chemical compound C=1C=CC=CC=1C(OCC(=O)NN)C1=CC=CC=C1 LNJHYWAAVRVKIC-UHFFFAOYSA-N 0.000 description 1
- NBPLLPBYZXYAMN-UHFFFAOYSA-N 2-ethoxyacetohydrazide Chemical compound CCOCC(=O)NN NBPLLPBYZXYAMN-UHFFFAOYSA-N 0.000 description 1
- HYXCKBUBQWDMFP-UHFFFAOYSA-N 2-fluoroacetohydrazide Chemical compound NNC(=O)CF HYXCKBUBQWDMFP-UHFFFAOYSA-N 0.000 description 1
- HXRPUTVWJDNSDJ-UHFFFAOYSA-N 2-hydroxy-2-methylpropanehydrazide Chemical compound CC(C)(O)C(=O)NN HXRPUTVWJDNSDJ-UHFFFAOYSA-N 0.000 description 1
- LIUCWHQVLKSECA-UHFFFAOYSA-N 2-hydroxyacetohydrazide Chemical compound NNC(=O)CO LIUCWHQVLKSECA-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1735270 | 1970-11-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL72358B1 true PL72358B1 (en, 2012) | 1974-06-29 |
Family
ID=4424771
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1971151699A PL72358B1 (en, 2012) | 1970-11-23 | 1971-11-22 |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4427590A (en, 2012) |
| JP (2) | JPS5619352B1 (en, 2012) |
| AT (1) | AT313282B (en, 2012) |
| AU (1) | AU465108B2 (en, 2012) |
| BE (1) | BE775558A (en, 2012) |
| CA (1) | CA983027A (en, 2012) |
| CS (1) | CS178091B2 (en, 2012) |
| DE (1) | DE2156472A1 (en, 2012) |
| DK (1) | DK138854B (en, 2012) |
| FI (1) | FI52864C (en, 2012) |
| FR (1) | FR2115265B1 (en, 2012) |
| GB (1) | GB1377650A (en, 2012) |
| GT (1) | GT197853300A (en, 2012) |
| HK (1) | HK16078A (en, 2012) |
| HU (1) | HU165317B (en, 2012) |
| IE (1) | IE35811B1 (en, 2012) |
| IL (1) | IL38151A (en, 2012) |
| KE (1) | KE2827A (en, 2012) |
| MY (1) | MY7800232A (en, 2012) |
| NL (1) | NL174252C (en, 2012) |
| PL (1) | PL72358B1 (en, 2012) |
| SE (1) | SE389499B (en, 2012) |
| SU (2) | SU523639A3 (en, 2012) |
| YU (1) | YU293871A (en, 2012) |
| ZA (1) | ZA717721B (en, 2012) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4902794A (en) * | 1971-04-28 | 1990-02-20 | The Upjohn Company | Triazolo-benzodiazepines |
| GB1381158A (en) * | 1971-09-13 | 1975-01-22 | Upjohn Co | Benzodiazepines and the manufacture thereof |
| GB1377230A (en) * | 1971-09-13 | 1974-12-11 | Upjohn Co | 4h-s-triazolo -4,3-a- 1,4-benzodiazepines |
| US3767660A (en) * | 1971-09-13 | 1973-10-23 | Upjohn Co | 4h-s-triazolo(4,3-a)(1,4)benzodiazepines |
| US4009175A (en) * | 1976-03-15 | 1977-02-22 | The Upjohn Company | 1-[(Aminooxy)-methyl]-6-substituted-4H-s-triazolo[4,3-a][1,4] benzodiazepines |
| DE3332830A1 (de) * | 1982-09-16 | 1984-03-22 | The Upjohn Co., 49001 Kalamazoo, Mich. | Verwendung von benzodiazepinen zur bekaempfung oder bei der behandlung von panikzustaenden |
| DE3328255A1 (de) * | 1983-08-04 | 1985-02-21 | Siemens AG, 1000 Berlin und 8000 München | Klebestation fuer einen schnelldrucker |
| GB9911152D0 (en) * | 1999-05-14 | 1999-07-14 | Glaxo Group Ltd | Short-acting benzodiazepines |
| US7160880B1 (en) | 1999-05-14 | 2007-01-09 | Cenes Limited | Short-acting benzodiazepines |
| CN104059071B (zh) | 2006-07-10 | 2016-06-22 | Paion英国有限公司 | 短效苯并二氮杂*盐及其多晶型 |
| EP2450039A1 (en) | 2010-11-08 | 2012-05-09 | PAION UK Ltd. | Dosing regimen for sedation with CNS 7056 (Remimazolam) |
| AR094963A1 (es) | 2013-03-04 | 2015-09-09 | Ono Pharmaceutical Co | Reacción de oxidación excelente en el índice de conversión |
| TW201945346A (zh) | 2018-04-10 | 2019-12-01 | 德商拜耳廠股份有限公司 | 2,4,5-三取代的1,2,4-三唑酮之製備方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3987052A (en) * | 1969-03-17 | 1976-10-19 | The Upjohn Company | 6-Phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines |
| FR2022598A1 (en) * | 1969-11-04 | 1970-07-31 | Pakeda Chemical Ind | Sedative chloro-phenyl-triazolobenzodiazepines |
| GB1331015A (en) | 1971-04-28 | 1973-09-19 | Upjohn Co | 1-substituted-6-phenyl-4h-s-triazolo-4,3-a-1,4-benzodiazepines |
| US4141902A (en) | 1971-04-28 | 1979-02-27 | The Upjohn Company | 1-Halomethyl-6-phenyl-4H-s-[4,3-a][1,4]benzodiazepines |
| US3681343A (en) | 1971-05-11 | 1972-08-01 | Upjohn Co | 6-phenyl-s-triazolo{8 4,3-a{9 {8 1,4{9 {0 benzodiazepines |
-
1971
- 1971-11-13 DE DE19712156472 patent/DE2156472A1/de not_active Withdrawn
- 1971-11-15 IE IE1437/71A patent/IE35811B1/xx unknown
- 1971-11-15 DK DK560071AA patent/DK138854B/da not_active IP Right Cessation
- 1971-11-15 IL IL38151A patent/IL38151A/xx unknown
- 1971-11-16 FI FI713282A patent/FI52864C/fi active
- 1971-11-16 ZA ZA717721A patent/ZA717721B/xx unknown
- 1971-11-16 NL NLAANVRAGE7115785,A patent/NL174252C/xx not_active IP Right Cessation
- 1971-11-16 SE SE7114644A patent/SE389499B/xx unknown
- 1971-11-17 US US05/199,770 patent/US4427590A/en not_active Expired - Lifetime
- 1971-11-19 FR FR7141474A patent/FR2115265B1/fr not_active Expired
- 1971-11-19 BE BE775558A patent/BE775558A/xx not_active IP Right Cessation
- 1971-11-20 JP JP9275971A patent/JPS5619352B1/ja active Pending
- 1971-11-22 AT AT1005471A patent/AT313282B/de not_active IP Right Cessation
- 1971-11-22 SU SU1716579A patent/SU523639A3/ru active
- 1971-11-22 CS CS8129A patent/CS178091B2/cs unknown
- 1971-11-22 CA CA128,212A patent/CA983027A/en not_active Expired
- 1971-11-22 HU HUCI1191A patent/HU165317B/hu unknown
- 1971-11-22 PL PL1971151699A patent/PL72358B1/pl unknown
- 1971-11-22 AU AU35966/71A patent/AU465108B2/en not_active Expired
- 1971-11-22 GB GB5404771A patent/GB1377650A/en not_active Expired
- 1971-11-22 YU YU02938/71A patent/YU293871A/xx unknown
-
1975
- 1975-08-01 SU SU7502163070A patent/SU568366A3/ru active
-
1978
- 1978-03-14 KE KE2827A patent/KE2827A/xx unknown
- 1978-03-23 HK HK160/78A patent/HK16078A/xx unknown
- 1978-07-19 GT GT197853300A patent/GT197853300A/es unknown
- 1978-12-30 MY MY232/78A patent/MY7800232A/xx unknown
-
1980
- 1980-04-02 JP JP55042074A patent/JPS5919956B2/ja not_active Expired
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