NO761800L - Isoindol-derivater. - Google Patents
Isoindol-derivater.Info
- Publication number
- NO761800L NO761800L NO761800A NO761800A NO761800L NO 761800 L NO761800 L NO 761800L NO 761800 A NO761800 A NO 761800A NO 761800 A NO761800 A NO 761800A NO 761800 L NO761800 L NO 761800L
- Authority
- NO
- Norway
- Prior art keywords
- hydrogen
- alkyl
- chloro
- carboxylic acid
- phenylisoindole
- Prior art date
Links
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical class C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims description 151
- 239000001257 hydrogen Substances 0.000 claims description 107
- 229910052739 hydrogen Inorganic materials 0.000 claims description 107
- 125000000217 alkyl group Chemical group 0.000 claims description 77
- 150000002431 hydrogen Chemical class 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 60
- 229910052757 nitrogen Inorganic materials 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 45
- 238000002360 preparation method Methods 0.000 claims description 32
- -1 5-chloro-phenylisoindole-1-carboxylic acid-[2-(diethylamino)ethyl]amide Chemical compound 0.000 claims description 31
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 30
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 28
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 21
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 19
- 150000001412 amines Chemical class 0.000 claims description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
- 239000001301 oxygen Substances 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 18
- 229910052740 iodine Inorganic materials 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 150000002829 nitrogen Chemical group 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 150000002518 isoindoles Chemical class 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- 150000001408 amides Chemical class 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 9
- UUHTYODRJWRZCB-UHFFFAOYSA-N 5-chloro-2-methyl-3-phenylisoindole-1-carboxylic acid Chemical compound CN1C(C(O)=O)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 UUHTYODRJWRZCB-UHFFFAOYSA-N 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 6
- 239000005977 Ethylene Substances 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 6
- LRIZBGDTMIOPHH-UHFFFAOYSA-N 5-chloro-3-phenyl-2h-isoindole-1-carboxylic acid Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)O)NC=1C1=CC=CC=C1 LRIZBGDTMIOPHH-UHFFFAOYSA-N 0.000 claims description 4
- RNHLBUFDRILXDK-UHFFFAOYSA-N 5-chloro-n-[3-(methylamino)propyl]-3-phenyl-2h-isoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)NCCCNC)NC=1C1=CC=CC=C1 RNHLBUFDRILXDK-UHFFFAOYSA-N 0.000 claims description 4
- 230000001539 anorectic effect Effects 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 4
- XPAQBYUCYWWAAA-UHFFFAOYSA-N 2-(diethylamino)ethyl 5-chloro-3-phenyl-2h-isoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCCN(CC)CC)NC=1C1=CC=CC=C1 XPAQBYUCYWWAAA-UHFFFAOYSA-N 0.000 claims description 3
- FJQLBKPXABCDRY-UHFFFAOYSA-N 2-(dimethylamino)ethyl 5-chloro-3-phenyl-2h-isoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCCN(C)C)NC=1C1=CC=CC=C1 FJQLBKPXABCDRY-UHFFFAOYSA-N 0.000 claims description 3
- MUCJRYKTWUILSV-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-[2-(diethylamino)ethyl]-2h-isoindole-1-carboxamide Chemical compound C=12C=CC=CC2=C(C(=O)NCCN(CC)CC)NC=1C1=CC=C(Cl)C=C1 MUCJRYKTWUILSV-UHFFFAOYSA-N 0.000 claims description 3
- OQCCUFHCZATRFU-UHFFFAOYSA-N 3-(diethylamino)propyl 5-chloro-3-phenyl-2h-isoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCCCN(CC)CC)NC=1C1=CC=CC=C1 OQCCUFHCZATRFU-UHFFFAOYSA-N 0.000 claims description 3
- IRBFAMVDBSGAKF-UHFFFAOYSA-N 5-chloro-2-methyl-3-phenyl-n-[4-(propan-2-ylamino)pentyl]isoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)NCCCC(C)NC(C)C)N(C)C=1C1=CC=CC=C1 IRBFAMVDBSGAKF-UHFFFAOYSA-N 0.000 claims description 3
- CXRCAJUTAAKNOS-UHFFFAOYSA-N 5-chloro-3-(4-chlorophenyl)-N-[2-(diethylamino)ethyl]-2H-isoindole-1-carboxamide Chemical compound C(C)N(CCNC(=O)C=1NC(=C2C=C(C=CC12)Cl)C1=CC=C(C=C1)Cl)CC CXRCAJUTAAKNOS-UHFFFAOYSA-N 0.000 claims description 3
- GQSGOMNEFVUXGL-UHFFFAOYSA-N 5-chloro-3-phenyl-N-(2-piperidin-1-ylethyl)-2H-isoindole-1-carboxamide Chemical compound N1(CCCCC1)CCNC(=O)C=1NC(=C2C=C(C=CC12)Cl)C1=CC=CC=C1 GQSGOMNEFVUXGL-UHFFFAOYSA-N 0.000 claims description 3
- GTCPNFLPDBOQRL-UHFFFAOYSA-N 5-chloro-3-phenyl-N-(2-pyrrolidin-1-ylethyl)-2H-isoindole-1-carboxamide Chemical compound N1(CCCC1)CCNC(=O)C=1NC(=C2C=C(C=CC12)Cl)C1=CC=CC=C1 GTCPNFLPDBOQRL-UHFFFAOYSA-N 0.000 claims description 3
- DZKZBIOIXYVZKH-UHFFFAOYSA-N 5-chloro-N-(2-morpholin-4-ylethyl)-3-phenyl-2H-isoindole-1-carboxamide Chemical compound O1CCN(CC1)CCNC(=O)C=1NC(=C2C=C(C=CC12)Cl)C1=CC=CC=C1 DZKZBIOIXYVZKH-UHFFFAOYSA-N 0.000 claims description 3
- DOOUJGNBKQRJRQ-UHFFFAOYSA-N 5-chloro-N-[3-(diethylamino)propyl]-3-phenyl-2H-isoindole-1-carboxamide Chemical compound C(C)N(CCCNC(=O)C=1NC(=C2C=C(C=CC=12)Cl)C1=CC=CC=C1)CC DOOUJGNBKQRJRQ-UHFFFAOYSA-N 0.000 claims description 3
- KZBFEEZUPXTKTF-UHFFFAOYSA-N 5-chloro-n-[2-(diethylamino)ethyl]-2-methyl-3-phenylisoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)NCCN(CC)CC)N(C)C=1C1=CC=CC=C1 KZBFEEZUPXTKTF-UHFFFAOYSA-N 0.000 claims description 3
- ZABSMRRSNIMQGK-UHFFFAOYSA-N 5-chloro-n-[2-(diethylamino)ethyl]-3-phenyl-2h-isoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)NCCN(CC)CC)NC=1C1=CC=CC=C1 ZABSMRRSNIMQGK-UHFFFAOYSA-N 0.000 claims description 3
- LSOOGFKMPCJHQH-UHFFFAOYSA-N 5-chloro-n-[2-(diethylamino)ethyl]-n-methyl-3-phenyl-2h-isoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)N(C)CCN(CC)CC)NC=1C1=CC=CC=C1 LSOOGFKMPCJHQH-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 150000004985 diamines Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical group CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 2
- DJCYGBSVNUYUMD-UHFFFAOYSA-N 2-morpholin-4-ylethyl 5-chloro-3-phenyl-2h-isoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCCN2CCOCC2)NC=1C1=CC=CC=C1 DJCYGBSVNUYUMD-UHFFFAOYSA-N 0.000 claims description 2
- MOUPUNCLIKZINP-UHFFFAOYSA-N 3-(4-chlorophenyl)-2h-isoindole-1-carboxylic acid Chemical compound C=12C=CC=CC2=C(C(=O)O)NC=1C1=CC=C(Cl)C=C1 MOUPUNCLIKZINP-UHFFFAOYSA-N 0.000 claims description 2
- SSGWRALMOKDHBG-UHFFFAOYSA-N 5,7-dichloro-N-[2-(diethylamino)ethyl]-3-phenyl-2H-isoindole-1-carboxamide Chemical compound C(C)N(CCNC(=O)C=1NC(=C2C=C(C=C(C=12)Cl)Cl)C1=CC=CC=C1)CC SSGWRALMOKDHBG-UHFFFAOYSA-N 0.000 claims description 2
- VINCJLGOCXYFCY-UHFFFAOYSA-N 5-chloro-N-[3-(dimethylamino)propyl]-3-phenyl-2H-isoindole-1-carboxamide Chemical compound CN(CCCNC(=O)C=1NC(=C2C=C(C=CC12)Cl)C1=CC=CC=C1)C VINCJLGOCXYFCY-UHFFFAOYSA-N 0.000 claims description 2
- SYLTYBLMOGHMGL-UHFFFAOYSA-N 5-chloro-n-[2-(diethylamino)ethyl]-n,2-dimethyl-3-phenylisoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)N(C)CCN(CC)CC)N(C)C=1C1=CC=CC=C1 SYLTYBLMOGHMGL-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims description 2
- WSZQBQREHIXSGW-UHFFFAOYSA-N 5-chloro-N-[2-(diethylamino)ethyl]-3-(2-fluorophenyl)-2H-isoindole-1-carboxamide Chemical compound C(C)N(CCNC(=O)C=1NC(=C2C=C(C=CC12)Cl)C1=C(C=CC=C1)F)CC WSZQBQREHIXSGW-UHFFFAOYSA-N 0.000 claims 2
- XAPHFWGOVHENTI-UHFFFAOYSA-N n-(3-aminopropyl)-5-chloro-2-methyl-3-phenylisoindole-1-carboxamide Chemical compound CN1C(C(=O)NCCCN)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 XAPHFWGOVHENTI-UHFFFAOYSA-N 0.000 claims 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- JFYSRVQADVCYMF-UHFFFAOYSA-N 5-chloro-2-ethyl-3-phenylisoindole-1-carboxylic acid Chemical compound CCN1C(C(O)=O)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 JFYSRVQADVCYMF-UHFFFAOYSA-N 0.000 claims 1
- QSMYPUFUQGPETO-UHFFFAOYSA-N 5-chloro-N-[3-(4-methylpiperazin-1-yl)propyl]-3-phenyl-2H-isoindole-1-carboxamide Chemical compound CN1CCN(CC1)CCCNC(=O)C=1NC(=C2C=C(C=CC12)Cl)C1=CC=CC=C1 QSMYPUFUQGPETO-UHFFFAOYSA-N 0.000 claims 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 165
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 120
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 104
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 83
- 239000000243 solution Substances 0.000 description 68
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 65
- 238000006243 chemical reaction Methods 0.000 description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 42
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- 229910052938 sodium sulfate Inorganic materials 0.000 description 31
- 235000011152 sodium sulphate Nutrition 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 239000002585 base Substances 0.000 description 29
- 239000000203 mixture Substances 0.000 description 28
- 239000003960 organic solvent Substances 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 23
- 238000001953 recrystallisation Methods 0.000 description 23
- 238000010992 reflux Methods 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 21
- 239000012312 sodium hydride Substances 0.000 description 21
- 229910000104 sodium hydride Inorganic materials 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 20
- 239000011780 sodium chloride Substances 0.000 description 20
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 229910052786 argon Inorganic materials 0.000 description 17
- 238000001816 cooling Methods 0.000 description 17
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 17
- 239000013078 crystal Substances 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- 238000000354 decomposition reaction Methods 0.000 description 15
- 239000005457 ice water Substances 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 229910052783 alkali metal Inorganic materials 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000003638 chemical reducing agent Substances 0.000 description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 description 8
- 239000011591 potassium Substances 0.000 description 8
- 229910052700 potassium Inorganic materials 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 7
- 239000000908 ammonium hydroxide Substances 0.000 description 7
- 239000012047 saturated solution Substances 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
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000538 analytical sample Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 6
- 239000002480 mineral oil Substances 0.000 description 6
- 235000010446 mineral oil Nutrition 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 238000001665 trituration Methods 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
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- RXFXNCMMLGHCQY-UHFFFAOYSA-N 5-chloro-3-(2-fluorophenyl)-2h-isoindole-1-carboxylic acid Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)O)NC=1C1=CC=CC=C1F RXFXNCMMLGHCQY-UHFFFAOYSA-N 0.000 description 1
- JBOJONNRTKZGPT-UHFFFAOYSA-N 5-chloro-N-(3-hydroxypropyl)-2-methyl-3-phenylisoindole-1-carboxamide Chemical compound CN1C(C(=O)NCCCO)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 JBOJONNRTKZGPT-UHFFFAOYSA-N 0.000 description 1
- QAVFBYXWPUTQEC-UHFFFAOYSA-N 5-chloro-n-(3-chloropropyl)-n,2-dimethyl-3-phenylisoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)N(CCCCl)C)N(C)C=1C1=CC=CC=C1 QAVFBYXWPUTQEC-UHFFFAOYSA-N 0.000 description 1
- YAAXNCIROFXEFR-UHFFFAOYSA-N 5-chloro-n-[2-(diethylamino)ethyl]-2-ethyl-3-phenylisoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)NCCN(CC)CC)N(CC)C=1C1=CC=CC=C1 YAAXNCIROFXEFR-UHFFFAOYSA-N 0.000 description 1
- DTULHZPWOSQNIG-UHFFFAOYSA-N 5-chloro-n-[2-(diethylamino)ethyl]-n-methyl-3-phenyl-2h-isoindole-1-carboxamide;hydrochloride Chemical compound Cl.C=12C=C(Cl)C=CC2=C(C(=O)N(C)CCN(CC)CC)NC=1C1=CC=CC=C1 DTULHZPWOSQNIG-UHFFFAOYSA-N 0.000 description 1
- SJVGFKBLUYAEOK-SFHVURJKSA-N 6-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrimidine-4-carbonitrile Chemical compound FC=1C=C(C=C(C=1)F)[C@@H]1CC=NN1C(=O)C1CCN(CC1)C1=CC(=NC=N1)C#N SJVGFKBLUYAEOK-SFHVURJKSA-N 0.000 description 1
- RIUVIMLHUDDDHK-UHFFFAOYSA-N 7-chloro-1-(3-chloropropyl)-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CCCCl)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 RIUVIMLHUDDDHK-UHFFFAOYSA-N 0.000 description 1
- CETQIDCZCLTIAY-UHFFFAOYSA-N 7-chloro-1-[3-(oxan-2-yloxy)propyl]-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1CN=C(C=2C=CC=CC=2)C2=CC(Cl)=CC=C2N1CCCOC1CCCCO1 CETQIDCZCLTIAY-UHFFFAOYSA-N 0.000 description 1
- NREZCHNRKHPEMI-UHFFFAOYSA-N 7-chloro-1-methyl-2-oxo-5-phenyl-3h-1,4-benzodiazepine-3-carboxylic acid Chemical compound N=1C(C(O)=O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 NREZCHNRKHPEMI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 1
- 240000001546 Byrsonima crassifolia Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 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 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- ZGSDJMADBJCNPN-UHFFFAOYSA-N [S-][NH3+] Chemical compound [S-][NH3+] ZGSDJMADBJCNPN-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 235000021407 appetite control Nutrition 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 239000012435 aralkylating agent Substances 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- UAZDIGCOBKKMPU-UHFFFAOYSA-O azanium;azide Chemical compound [NH4+].[N-]=[N+]=[N-] UAZDIGCOBKKMPU-UHFFFAOYSA-O 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- VOQJNXLHWBMMSB-UHFFFAOYSA-N benzyl 2-[3-[(5-chloro-3-phenyl-2h-isoindole-1-carbonyl)amino]propylamino]acetate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)NCCCNCC(=O)OCC=2C=CC=CC=2)NC=1C1=CC=CC=C1 VOQJNXLHWBMMSB-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UETLMBWMVIQIGU-UHFFFAOYSA-N calcium azide Chemical compound [Ca+2].[N-]=[N+]=[N-].[N-]=[N+]=[N-] UETLMBWMVIQIGU-UHFFFAOYSA-N 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
- OZECDDHOAMNMQI-UHFFFAOYSA-H cerium(3+);trisulfate Chemical compound [Ce+3].[Ce+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O OZECDDHOAMNMQI-UHFFFAOYSA-H 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- VRZVPALEJCLXPR-UHFFFAOYSA-N ethyl 4-methylbenzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C=C1 VRZVPALEJCLXPR-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- UTWGRMYWDUMKNY-UHFFFAOYSA-N indole-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)C=CC2=C1 UTWGRMYWDUMKNY-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical compound [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- LLCOIQRNSJBFSN-UHFFFAOYSA-N methane;sulfurochloridic acid Chemical compound C.OS(Cl)(=O)=O LLCOIQRNSJBFSN-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- LXRRWSHNMHVHFK-UHFFFAOYSA-N n-(3-aminopropyl)-5-chloro-2-methyl-3-phenylisoindole-1-carboxamide;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.CN1C(C(=O)NCCCN)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 LXRRWSHNMHVHFK-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- PZHNNJXWQYFUTD-UHFFFAOYSA-N phosphorus triiodide Chemical compound IP(I)I PZHNNJXWQYFUTD-UHFFFAOYSA-N 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 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
- 239000000829 suppository Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
-
- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH645476 | 1976-05-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO761800L true NO761800L (no) | 1977-11-22 |
Family
ID=4309886
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO761800A NO761800L (no) | 1976-05-21 | 1976-05-26 | Isoindol-derivater. |
Country Status (5)
| Country | Link |
|---|---|
| DK (1) | DK232976A (xx) |
| FI (1) | FI761491A (xx) |
| NO (1) | NO761800L (xx) |
| SE (1) | SE411901B (xx) |
| ZA (1) | ZA772871B (xx) |
-
1976
- 1976-05-26 SE SE7606034A patent/SE411901B/xx unknown
- 1976-05-26 NO NO761800A patent/NO761800L/no unknown
- 1976-05-26 DK DK232976A patent/DK232976A/da not_active Application Discontinuation
- 1976-05-26 FI FI761491A patent/FI761491A/fi not_active Application Discontinuation
-
1977
- 1977-05-13 ZA ZA00772871A patent/ZA772871B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK232976A (da) | 1977-11-22 |
| FI761491A (xx) | 1977-11-22 |
| SE411901B (sv) | 1980-02-11 |
| SE7606034L (sv) | 1977-11-27 |
| ZA772871B (en) | 1978-04-26 |
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