IL27764A - Tetrahydroquinazolines,their preparation and use - Google Patents
Tetrahydroquinazolines,their preparation and useInfo
- Publication number
- IL27764A IL27764A IL27764A IL2776467A IL27764A IL 27764 A IL27764 A IL 27764A IL 27764 A IL27764 A IL 27764A IL 2776467 A IL2776467 A IL 2776467A IL 27764 A IL27764 A IL 27764A
- Authority
- IL
- Israel
- Prior art keywords
- acid
- tetrahydroquinazoline
- formula
- dibromo
- compounds
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 18
- 238000000034 method Methods 0.000 claims description 53
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 239000003960 organic solvent Substances 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 8
- 239000008298 dragée Substances 0.000 claims description 8
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 8
- 229910052987 metal hydride Inorganic materials 0.000 claims description 8
- 150000004681 metal hydrides Chemical class 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 7
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- 235000002906 tartaric acid Nutrition 0.000 claims description 7
- 239000011975 tartaric acid Substances 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 230000031709 bromination Effects 0.000 claims description 4
- 238000005893 bromination reaction Methods 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- 229960000583 acetic acid Drugs 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 238000005660 chlorination reaction Methods 0.000 claims description 3
- 239000012362 glacial acetic acid Substances 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 125000005350 hydroxycycloalkyl group Chemical group 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000006408 oxalic acid Nutrition 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 235000011007 phosphoric acid Nutrition 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 239000001117 sulphuric acid Substances 0.000 claims description 2
- 235000011149 sulphuric acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims 2
- 229960004132 diethyl ether Drugs 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 239000000243 solution Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
- 239000006188 syrup Substances 0.000 description 11
- 235000020357 syrup Nutrition 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
- -1 e.g. Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- 229960000443 hydrochloric acid Drugs 0.000 description 6
- 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
- 239000008101 lactose Substances 0.000 description 5
- 229920001592 potato starch Polymers 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 2
- PKORYTIUMAOPED-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinazoline Chemical class C1=CC=C2NCNCC2=C1 PKORYTIUMAOPED-UHFFFAOYSA-N 0.000 description 2
- GVOYKJPMUUJXBS-UHFFFAOYSA-N 2-(aminomethyl)aniline Chemical class NCC1=CC=CC=C1N GVOYKJPMUUJXBS-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- 235000011034 Rubus glaucus Nutrition 0.000 description 2
- 244000235659 Rubus idaeus Species 0.000 description 2
- 235000009122 Rubus idaeus Nutrition 0.000 description 2
- 244000273928 Zingiber officinale Species 0.000 description 2
- 235000006886 Zingiber officinale Nutrition 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 235000008397 ginger Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229940041616 menthol Drugs 0.000 description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- KNDQIYUBRSOTRO-UHFFFAOYSA-N (2-amino-3,5-dibromophenyl)methyl-(2-methylpropyl)azanium bromide Chemical compound [Br-].C(C(C)C)[NH2+]CC1=C(C(=CC(=C1)Br)Br)N KNDQIYUBRSOTRO-UHFFFAOYSA-N 0.000 description 1
- BYWIQEGCFWEMJP-ACMTZBLWSA-N (2-amino-3,5-dibromophenyl)methyl-[(1S,3S)-3-hydroxycyclohexyl]azanium chloride Chemical compound [Cl-].O[C@@H]1C[C@H](CCC1)[NH2+]CC1=C(C(=CC(=C1)Br)Br)N BYWIQEGCFWEMJP-ACMTZBLWSA-N 0.000 description 1
- LGACUMPRRMLUFZ-UHFFFAOYSA-N 1,4-dihydroquinazoline Chemical compound C1=CC=C2CN=CNC2=C1 LGACUMPRRMLUFZ-UHFFFAOYSA-N 0.000 description 1
- KLCDQSGLLRINHY-UHFFFAOYSA-N 1-phenyldiazenylnaphthalen-2-amine Chemical compound NC1=CC=C2C=CC=CC2=C1N=NC1=CC=CC=C1 KLCDQSGLLRINHY-UHFFFAOYSA-N 0.000 description 1
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical class NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 1
- WKUXZPJJBMVRON-UHFFFAOYSA-N 2-[(benzylamino)methyl]-4-chloroaniline Chemical compound C(C1=CC=CC=C1)NCC1=C(C=CC(=C1)Cl)N WKUXZPJJBMVRON-UHFFFAOYSA-N 0.000 description 1
- VXWYQEYFYNAZOD-UHFFFAOYSA-N 2-[3-[(4,4-difluoropiperidin-1-yl)methyl]-4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound FC1(F)CCN(CC2=NN(CC(=O)N3CCC4=C(C3)N=NN4)C=C2C2=CN=C(NC3CC4=C(C3)C=CC=C4)N=C2)CC1 VXWYQEYFYNAZOD-UHFFFAOYSA-N 0.000 description 1
- IKOKHHBZFDFMJW-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(2-morpholin-4-ylethoxy)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCCN1CCOCC1 IKOKHHBZFDFMJW-UHFFFAOYSA-N 0.000 description 1
- HSGGWUGAVYTADI-UHFFFAOYSA-N 5-chloro-n-cyclohexyl-2-(methylamino)benzamide Chemical compound CNC1=CC=C(Cl)C=C1C(=O)NC1CCCCC1 HSGGWUGAVYTADI-UHFFFAOYSA-N 0.000 description 1
- QAAKUWHMWFVTFS-UHFFFAOYSA-N 6,8-dibromo-3-cyclohexyl-2,4-dihydro-1h-quinazoline Chemical compound C1C2=CC(Br)=CC(Br)=C2NCN1C1CCCCC1 QAAKUWHMWFVTFS-UHFFFAOYSA-N 0.000 description 1
- UZVFOBCSRACABZ-UHFFFAOYSA-N 6-chloro-3-cyclohexyl-2,4-dihydro-1H-quinazoline Chemical compound ClC=1C=C2CN(CNC2=CC1)C1CCCCC1 UZVFOBCSRACABZ-UHFFFAOYSA-N 0.000 description 1
- SKTSKCZLRCFZGM-UHFFFAOYSA-N 7-chloro-2-methyl-3-propyl-2,4-dihydro-1H-quinazoline Chemical compound ClC1=CC=C2CN(C(NC2=C1)C)CCC SKTSKCZLRCFZGM-UHFFFAOYSA-N 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- DIMFPIIENMXCOR-UHFFFAOYSA-N C(C(C)C)NCC1=C(C=CC(=C1)Cl)N Chemical compound C(C(C)C)NCC1=C(C=CC(=C1)Cl)N DIMFPIIENMXCOR-UHFFFAOYSA-N 0.000 description 1
- PIMCMPQWMLWLEV-UHFFFAOYSA-N C(C)(C)NCC1=C(C=CC(=C1)Cl)N Chemical compound C(C)(C)NCC1=C(C=CC(=C1)Cl)N PIMCMPQWMLWLEV-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 229910001853 inorganic hydroxide Inorganic materials 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous 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
- 239000008096 xylene Substances 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DET0030948 | 1966-04-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL27764A true IL27764A (en) | 1971-02-25 |
Family
ID=36887743
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL27764A IL27764A (en) | 1966-04-20 | 1967-04-10 | Tetrahydroquinazolines,their preparation and use |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US3454574A (de) |
| BE (1) | BE697188A (de) |
| CH (5) | CH483433A (de) |
| CS (1) | CS162434B1 (de) |
| DE (1) | DE1620541C3 (de) |
| DK (1) | DK120345B (de) |
| ES (4) | ES339371A1 (de) |
| FI (1) | FI48929C (de) |
| FR (2) | FR1524445A (de) |
| GB (1) | GB1131164A (de) |
| GR (1) | GR33644B (de) |
| IL (1) | IL27764A (de) |
| NL (2) | NL6705206A (de) |
| SE (1) | SE323685B (de) |
| YU (4) | YU32364B (de) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5924990B2 (ja) * | 1979-11-21 | 1984-06-13 | 協和醗酵工業株式会社 | 新規なピペリジン誘導体 |
| US4710502A (en) * | 1985-11-04 | 1987-12-01 | American Cyanamid Company | 3-heteroarylalkyl-4-quinazolinones |
| US4753944A (en) * | 1985-11-04 | 1988-06-28 | American Cyanamid Company | Pharmaceutical methods of using 3-heteroarylalkyl-4-quinazolinones |
| CS272018B1 (en) * | 1988-11-01 | 1990-12-13 | Fisnerova Ludmila | Ethereal derivatives of 4/3h/-quinazolinone |
| US20070104709A1 (en) * | 2003-08-06 | 2007-05-10 | Xiaodong Li | T1r hetero-oligomeric taste receptors, cell lines that express said receptors, and taste compounds |
| DK3235811T3 (en) | 2006-04-21 | 2018-11-12 | Senomyx Inc | PROCEDURE FOR THE PREPARATION OF OXALAMIDS |
| CN102898383A (zh) * | 2012-11-16 | 2013-01-30 | 葛长乐 | 一种氨溴索反式杂质6,8-二溴-3-(反式-4-羟基环己基)-1,2,3,4-四氢喹唑啉的制备方法 |
-
0
- NL NL131479D patent/NL131479C/xx active
-
1966
- 1966-04-20 DE DE1620541A patent/DE1620541C3/de not_active Expired
-
1967
- 1967-03-30 DK DK173367AA patent/DK120345B/da unknown
- 1967-04-06 CH CH483567A patent/CH483433A/de not_active IP Right Cessation
- 1967-04-06 CH CH895370A patent/CH508637A/de not_active IP Right Cessation
- 1967-04-06 CH CH1648369A patent/CH493533A/de not_active IP Right Cessation
- 1967-04-06 CH CH1648169A patent/CH493531A/de not_active IP Right Cessation
- 1967-04-06 CH CH1648269A patent/CH493532A/de not_active IP Right Cessation
- 1967-04-10 US US629417A patent/US3454574A/en not_active Expired - Lifetime
- 1967-04-10 IL IL27764A patent/IL27764A/en unknown
- 1967-04-13 NL NL6705206A patent/NL6705206A/xx unknown
- 1967-04-13 GB GB17098/67A patent/GB1131164A/en not_active Expired
- 1967-04-15 YU YU0756/67A patent/YU32364B/xx unknown
- 1967-04-15 ES ES339371A patent/ES339371A1/es not_active Expired
- 1967-04-17 ES ES339394A patent/ES339394A1/es not_active Expired
- 1967-04-18 FR FR103183A patent/FR1524445A/fr not_active Expired
- 1967-04-18 BE BE697188D patent/BE697188A/xx unknown
- 1967-04-18 ES ES339432A patent/ES339432A1/es not_active Expired
- 1967-04-18 FR FR103182A patent/FR6442M/fr not_active Expired
- 1967-04-19 ES ES339483A patent/ES339483A1/es not_active Expired
- 1967-04-19 GR GR670133644A patent/GR33644B/el unknown
- 1967-04-20 SE SE5557/67A patent/SE323685B/xx unknown
- 1967-04-20 FI FI671165A patent/FI48929C/fi active
-
1968
- 1968-09-25 CS CS6704A patent/CS162434B1/cs unknown
-
1973
- 1973-03-19 YU YU74173A patent/YU35587B/xx unknown
- 1973-03-19 YU YU742/73A patent/YU33957B/xx unknown
- 1973-03-19 YU YU740/73A patent/YU35360B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE323685B (de) | 1970-05-11 |
| GR33644B (el) | 1968-01-03 |
| ES339394A1 (es) | 1968-07-16 |
| YU75667A (en) | 1974-04-30 |
| CH493531A (de) | 1970-07-15 |
| CH493532A (de) | 1970-07-15 |
| NL131479C (de) | |
| YU33957B (en) | 1978-09-08 |
| YU32364B (en) | 1974-10-31 |
| YU74073A (en) | 1980-06-30 |
| ES339371A1 (es) | 1968-07-16 |
| YU35360B (en) | 1980-12-31 |
| FR1524445A (fr) | 1968-05-10 |
| BE697188A (de) | 1967-10-18 |
| CH483433A (de) | 1969-12-31 |
| YU35587B (en) | 1981-04-30 |
| DE1620541A1 (de) | 1970-04-16 |
| YU74173A (en) | 1980-09-25 |
| CH508637A (de) | 1971-06-15 |
| CS162434B1 (de) | 1975-07-15 |
| ES339483A1 (es) | 1968-07-16 |
| US3454574A (en) | 1969-07-08 |
| FR6442M (de) | 1968-11-12 |
| DE1620541B2 (de) | 1975-02-20 |
| YU74273A (en) | 1978-02-28 |
| GB1131164A (en) | 1968-10-23 |
| ES339432A1 (es) | 1968-07-16 |
| FI48929C (fi) | 1975-02-10 |
| NL6705206A (de) | 1967-10-23 |
| DK120345B (da) | 1971-05-17 |
| DE1620541C3 (de) | 1975-09-25 |
| FI48929B (de) | 1974-10-31 |
| CH493533A (de) | 1970-07-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK168485B1 (da) | Carbostyrilderivater, fremgangsmåde til fremstilling deraf og farmaceutisk præparat indeholdende et sådant carbostyrilderivat | |
| IL125076A (en) | Aza compounds, diazole cycloheptane and converted cyclooctane compounds and pharmaceutical preparations containing them | |
| NZ243777A (en) | Benzimidazolone derivatives; medicaments and preparatory processes | |
| DE1695124A1 (de) | Verfahren zur Herstellung von Tetrahydroazepinderivaten | |
| JPS5915911B2 (ja) | インドリン化合物の製造法 | |
| IE43901B1 (en) | Pharmaceutical compositions | |
| EP4163281A1 (de) | Herstellung von heterocyclischen verbindungen zur behandlung von erkrankungen und zwischenprodukte | |
| IL27764A (en) | Tetrahydroquinazolines,their preparation and use | |
| US4284555A (en) | 7-Chloro-8(substituted amino carbonyloxy)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines | |
| US3845060A (en) | 1-(1-(2,3-dihydro-2-benzofuryl)-alkyl)-4-aminohexahydroisonicotinic acid amides or nitriles | |
| CN113307791B (zh) | 嘧啶基哌嗪脲类trpv1拮抗/mor激动双靶点化合物及其制备方法和应用 | |
| US3373168A (en) | Certain benzazepinoxyridoindole compounds and their preparation | |
| JPS60158190A (ja) | ヒダントイン誘導体およびその製法ならびにそれを含有する医薬 | |
| US3530126A (en) | N-heterocyclic substituted cyclohexanes | |
| CS254971B2 (en) | Method of new bis-(piperazinyl-or homopiperazinyl)alkanes production | |
| US4016280A (en) | 4,4-Diarylpiperidine compositions and use | |
| US3647877A (en) | Aminopropionanilides | |
| US3823155A (en) | Imidazoline derivatives with diuretic properties | |
| US4130652A (en) | 2-(Iminoethylidene)-pyrrolidines and tautomeric 2-(aminoethenyl)-1-pyrrolines | |
| Corral et al. | N-Substituted 2-amino-1-(2-thienyl) ethanols as. beta.-adrenergic blocking agents | |
| US4010158A (en) | 1-(2'-Ethynyl-phenoxy)-2-hydroxy-3-butylamino-propanes and salts | |
| EP0000151B1 (de) | 1-Substituierte Aminoindoline, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zusammensetzungen | |
| JPS6130588A (ja) | ベンゾ〔ｃ〕〔１，８〕ナフチリジン、その製造方法及びその使用、並びにこれらの化合物を含有する調製剤 | |
| NZ196762A (en) | N,n-disubstituted-2-(isoxazol-4-yl)indol-3-ylethylamines | |
| US3576811A (en) | 1-alkyl-1-(beta-piperidino-ethyl)-1,2,3,4- tetrahydronaphthalen-2-ones |