IL29651A - Diazocycloalkenyl-isoindole derivatives and processes for he manufacture thereof - Google Patents
Diazocycloalkenyl-isoindole derivatives and processes for he manufacture thereofInfo
- Publication number
- IL29651A IL29651A IL29651A IL2965168A IL29651A IL 29651 A IL29651 A IL 29651A IL 29651 A IL29651 A IL 29651A IL 2965168 A IL2965168 A IL 2965168A IL 29651 A IL29651 A IL 29651A
- Authority
- IL
- Israel
- Prior art keywords
- formula
- compound
- hydroxy
- acid addition
- compounds
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 57
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 103
- 239000000203 mixture Substances 0.000 claims description 86
- 239000002253 acid Substances 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- -1 hydroxy- Chemical class 0.000 claims description 29
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 22
- 239000007787 solid Substances 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 17
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 14
- 239000007800 oxidant agent Substances 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 150000004985 diamines Chemical class 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 10
- 238000007254 oxidation reaction Methods 0.000 claims description 10
- 239000002841 Lewis acid Substances 0.000 claims description 9
- 150000001491 aromatic compounds Chemical class 0.000 claims description 9
- 150000007517 lewis acids Chemical class 0.000 claims description 9
- 230000003647 oxidation Effects 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 239000003368 psychostimulant agent Substances 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000000460 chlorine Chemical group 0.000 claims description 6
- 229910052801 chlorine Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 5
- HIHTVTATSKDEQF-UHFFFAOYSA-N 2-benzoylbenzaldehyde Chemical compound O=CC1=CC=CC=C1C(=O)C1=CC=CC=C1 HIHTVTATSKDEQF-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 5
- 230000001590 oxidative effect Effects 0.000 claims description 5
- XADYAGFTKHRPNE-UHFFFAOYSA-N 2-(4-methoxybenzoyl)benzaldehyde Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1C=O XADYAGFTKHRPNE-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical group [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 4
- JXLGASWYGQZVIN-UHFFFAOYSA-N 2-(1-phenyl-1,3-dihydroisoindol-2-yl)ethanamine Chemical compound NCCN1CC2=CC=CC=C2C1C1=CC=CC=C1 JXLGASWYGQZVIN-UHFFFAOYSA-N 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 3
- 230000000202 analgesic effect Effects 0.000 claims description 3
- 230000003501 anti-edematous effect Effects 0.000 claims description 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
- SOWOYMBNJVLWGP-UHFFFAOYSA-N isoindol-5-one Chemical compound O=C1C=CC2=CN=CC2=C1 SOWOYMBNJVLWGP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- YHWQUWUHLPRUID-UHFFFAOYSA-N (2-chlorophenyl)-[2-(4,5-dihydro-1h-imidazol-2-yl)phenyl]methanone Chemical compound ClC1=CC=CC=C1C(=O)C1=CC=CC=C1C1=NCCN1 YHWQUWUHLPRUID-UHFFFAOYSA-N 0.000 claims description 2
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 239000002221 antipyretic Substances 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 235000010265 sodium sulphite Nutrition 0.000 claims description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 17
- 125000004429 atom Chemical group 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- ZMGBTTPRSNEWIG-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)-1,3-dihydroisoindol-2-yl]ethanamine Chemical compound NCCN1C(C2=CC=CC=C2C1)C1=CC=C(C=C1)Cl ZMGBTTPRSNEWIG-UHFFFAOYSA-N 0.000 claims 1
- QJACTXOOIXRKBB-UHFFFAOYSA-N 2-[1-(4-methoxyphenyl)-1,3-dihydroisoindol-2-yl]ethanamine Chemical compound C1=CC(OC)=CC=C1C1C2=CC=CC=C2CN1CCN QJACTXOOIXRKBB-UHFFFAOYSA-N 0.000 claims 1
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- INCRYDPIDJWFEF-UHFFFAOYSA-N 5-(2-chlorophenyl)-2,3-dihydroimidazo[1,2-b]isoindol-5-ol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=CC=C1Cl INCRYDPIDJWFEF-UHFFFAOYSA-N 0.000 claims 1
- DZBZBMBZMOFMNN-UHFFFAOYSA-N 5-methoxy-5-phenyl-2,3-dihydroimidazo[2,1-a]isoindole Chemical compound N12CCN=C2C2=CC=CC=C2C1(OC)C1=CC=CC=C1 DZBZBMBZMOFMNN-UHFFFAOYSA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims 1
- 230000029936 alkylation Effects 0.000 claims 1
- 238000005804 alkylation reaction Methods 0.000 claims 1
- 230000000843 anti-fungal effect Effects 0.000 claims 1
- 230000001754 anti-pyretic effect Effects 0.000 claims 1
- 239000002249 anxiolytic agent Substances 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 229910052804 chromium Inorganic materials 0.000 claims 1
- 239000011651 chromium Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 210000003205 muscle Anatomy 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000001047 pyretic effect Effects 0.000 claims 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000000243 solution Substances 0.000 description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 66
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 63
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 58
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 238000002844 melting Methods 0.000 description 31
- 230000008018 melting Effects 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 238000001953 recrystallisation Methods 0.000 description 24
- 230000009102 absorption Effects 0.000 description 21
- 238000010521 absorption reaction Methods 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 21
- 239000000543 intermediate Substances 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 17
- DKUKKXXCBPICGC-UHFFFAOYSA-N [2-(4,5-dihydro-1h-imidazol-2-yl)phenyl]-phenylmethanone Chemical compound C=1C=CC=C(C=2NCCN=2)C=1C(=O)C1=CC=CC=C1 DKUKKXXCBPICGC-UHFFFAOYSA-N 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 14
- 239000003208 petroleum Substances 0.000 description 13
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 239000007795 chemical reaction product Substances 0.000 description 11
- 239000003960 organic solvent Substances 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 239000008096 xylene Substances 0.000 description 10
- 239000003708 ampul Substances 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 8
- 229930195733 hydrocarbon Natural products 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 150000002430 hydrocarbons Chemical class 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000008120 corn starch Substances 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 150000002978 peroxides Chemical class 0.000 description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 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 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 235000002906 tartaric acid Nutrition 0.000 description 5
- 239000011975 tartaric acid Substances 0.000 description 5
- DYNFCHNNOHNJFG-UHFFFAOYSA-N 2-formylbenzoic acid Chemical class OC(=O)C1=CC=CC=C1C=O DYNFCHNNOHNJFG-UHFFFAOYSA-N 0.000 description 4
- 235000019502 Orange oil Nutrition 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 150000005690 diesters Chemical class 0.000 description 4
- 150000002009 diols Chemical class 0.000 description 4
- 239000010502 orange oil Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- WKQOOBZACKJBQB-UHFFFAOYSA-N (2-chlorophenyl)-[2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=CC=C1C(O)C1=CC=CC=C1Cl WKQOOBZACKJBQB-UHFFFAOYSA-N 0.000 description 3
- REFMUVZBSRUILL-UHFFFAOYSA-N 2-(4-chlorobenzoyl)benzaldehyde Chemical compound C1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1C=O REFMUVZBSRUILL-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- QKDLQFSLLCQTOH-UHFFFAOYSA-N Trichodonin Natural products C1C(O)C2C3(COC(=O)C)C(C=O)C(C)(C)CCC3OC(=O)C22C(=O)C(=C)C1C2 QKDLQFSLLCQTOH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 229940117975 chromium trioxide Drugs 0.000 description 3
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 3
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 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
- 239000013078 crystal Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- UVNXNSUKKOLFBM-UHFFFAOYSA-N imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=CSC2=NC=CN21 UVNXNSUKKOLFBM-UHFFFAOYSA-N 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical class [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000006748 scratching Methods 0.000 description 3
- 230000002393 scratching effect Effects 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- NHZJEVSTGFERMD-UHFFFAOYSA-N (4-bromophenyl)-[2-(4,5-dihydro-1h-imidazol-2-yl)phenyl]methanone Chemical compound C1=CC(Br)=CC=C1C(=O)C1=CC=CC=C1C1=NCCN1 NHZJEVSTGFERMD-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- QZBXANMPSRVKIO-UHFFFAOYSA-N 2-(2-bromobenzoyl)benzaldehyde Chemical compound BrC1=CC=CC=C1C(=O)C1=CC=CC=C1C=O QZBXANMPSRVKIO-UHFFFAOYSA-N 0.000 description 2
- YTSWAXSUNMFKBE-UHFFFAOYSA-N 2-(2-chlorobenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1Cl YTSWAXSUNMFKBE-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
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- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
- 239000012808 vapor phase Substances 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/22—Radicals substituted by oxygen atoms
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Structures Of Non-Positive Displacement Pumps (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62696567A | 1967-03-30 | 1967-03-30 | |
| US639315A US3888846A (en) | 1967-03-30 | 1967-05-18 | Process for 2(2-(1,3-diazacycloalk-2-enyl))benzophenone derivatives and 1,3-diazacycloalkenyl(2,1-a)isoindole derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL29651A true IL29651A (en) | 1972-07-26 |
Family
ID=27090306
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL29651A IL29651A (en) | 1967-03-30 | 1968-03-18 | Diazocycloalkenyl-isoindole derivatives and processes for he manufacture thereof |
Country Status (8)
| Country | Link |
|---|---|
| JP (2) | JPS4843360B1 (nl) |
| ES (1) | ES352173A1 (nl) |
| IE (1) | IE31999B1 (nl) |
| IL (1) | IL29651A (nl) |
| MY (1) | MY7300459A (nl) |
| NO (5) | NO124111B (nl) |
| SE (1) | SE346318B (nl) |
| YU (1) | YU33929B (nl) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS50125392U (nl) * | 1974-03-30 | 1975-10-14 |
-
1968
- 1968-03-18 IL IL29651A patent/IL29651A/en unknown
- 1968-03-27 SE SE4081/68A patent/SE346318B/xx unknown
- 1968-03-29 IE IE366/68A patent/IE31999B1/xx unknown
- 1968-03-29 NO NO1212/68A patent/NO124111B/no unknown
- 1968-03-29 YU YU717/68A patent/YU33929B/xx unknown
-
1969
- 1969-05-19 ES ES352173A patent/ES352173A1/es not_active Expired
-
1970
- 1970-08-03 JP JP45067352A patent/JPS4843360B1/ja active Pending
-
1971
- 1971-10-12 NO NO03754/71*[A patent/NO127350B/no unknown
- 1971-10-12 NO NO03755/71*[A patent/NO127351B/no unknown
- 1971-10-12 NO NO03752/71*[A patent/NO127238B/no unknown
- 1971-10-12 NO NO03753/71*[A patent/NO127239B/no unknown
-
1973
- 1973-02-09 JP JP48016353A patent/JPS5017479B1/ja active Pending
- 1973-12-30 MY MY459/73A patent/MY7300459A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MY7300459A (en) | 1973-12-31 |
| NO127350B (nl) | 1973-06-12 |
| JPS5017479B1 (nl) | 1975-06-20 |
| IE31999L (en) | 1968-09-30 |
| ES352173A1 (es) | 1969-10-01 |
| JPS4843360B1 (nl) | 1973-12-18 |
| YU33929B (en) | 1978-09-08 |
| NO127351B (nl) | 1973-06-12 |
| YU71768A (en) | 1978-02-28 |
| NO127238B (nl) | 1973-05-28 |
| SE346318B (nl) | 1972-07-03 |
| NO124111B (nl) | 1972-03-06 |
| NO127239B (nl) | 1973-05-28 |
| IE31999B1 (en) | 1973-03-07 |
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