DD160535A5 - Verfahren zur herstellung neuer imidazobenzothiadiazepinen - Google Patents

Verfahren zur herstellung neuer imidazobenzothiadiazepinen Download PDF

Info

Publication number: DD160535A5
Authority: DD; German Democratic Republic
Prior art keywords: compound; hydrogen; lower alkyl; compounds; formula
Prior art date: 1980-06-12

Application number

DD81230728A

Other languages

German (de)

English (en)

Inventor

Isidoros Vlattas

Original Assignee

Ciba Geigy

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1980-06-12

Filing date

1981-06-11

Publication date

1983-09-07

1981-06-11 Application filed by Ciba Geigy filed Critical Ciba Geigy

1983-09-07 Publication of DD160535A5 publication Critical patent/DD160535A5/de

Links

238000000034 method Methods 0.000 title claims description 26
238000002360 preparation method Methods 0.000 title claims description 14
230000008569 process Effects 0.000 title claims description 11
150000001875 compounds Chemical class 0.000 claims abstract description 110
-1 cyano, carboxy Chemical group 0.000 claims abstract description 61
125000000217 alkyl group Chemical group 0.000 claims abstract description 49
150000003839 salts Chemical class 0.000 claims abstract description 41
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
239000001257 hydrogen Substances 0.000 claims abstract description 39
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 19
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 12
125000001589 carboacyl group Chemical group 0.000 claims abstract description 12
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 11
229910052783 alkali metal Chemical group 0.000 claims abstract description 10
150000001340 alkali metals Chemical group 0.000 claims abstract description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
125000005843 halogen group Chemical group 0.000 claims abstract description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 9
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 8
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims abstract description 5
125000002947 alkylene group Chemical group 0.000 claims abstract description 4
125000000858 thiocyanato group Chemical group *SC#N 0.000 claims abstract description 4
239000000203 mixture Substances 0.000 claims description 38
150000002431 hydrogen Chemical class 0.000 claims description 23
239000002253 acid Substances 0.000 claims description 21
239000000047 product Substances 0.000 claims description 19
KAOYLRLQZXRRBD-UHFFFAOYSA-N 1,2,3-benzothiadiazepine Chemical class S1N=NC=CC2=CC=CC=C12 KAOYLRLQZXRRBD-UHFFFAOYSA-N 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
150000001204 N-oxides Chemical class 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
150000004820 halides Chemical class 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 3
229910021529 ammonia Inorganic materials 0.000 claims description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
150000002334 glycols Chemical class 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
101000588924 Anthopleura elegantissima Delta-actitoxin-Ael1a Proteins 0.000 claims description 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
150000004703 alkoxides Chemical class 0.000 claims description 2
150000001408 amides Chemical class 0.000 claims description 2
150000001991 dicarboxylic acids Chemical class 0.000 claims description 2
230000003287 optical effect Effects 0.000 claims description 2
150000002924 oxiranes Chemical class 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
125000005102 carbonylalkoxy group Chemical group 0.000 claims 2
RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims 2
KKFDJZZADQONDE-UHFFFAOYSA-N (hydridonitrato)hydroxidocarbon(.) Chemical compound O[C]=N KKFDJZZADQONDE-UHFFFAOYSA-N 0.000 claims 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
239000007795 chemical reaction product Substances 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims 1
230000000701 neuroleptic effect Effects 0.000 abstract description 5
125000002768 hydroxyalkyl group Chemical group 0.000 abstract description 3
125000001651 cyanato group Chemical group [*]OC#N 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
235000002639 sodium chloride Nutrition 0.000 description 33
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
239000000155 melt Substances 0.000 description 20
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
241000282693 Cercopithecidae Species 0.000 description 16
239000007858 starting material Substances 0.000 description 16
241001465754 Metazoa Species 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
239000000725 suspension Substances 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 12
239000002585 base Substances 0.000 description 11
238000000354 decomposition reaction Methods 0.000 description 11
238000003756 stirring Methods 0.000 description 11
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
239000012299 nitrogen atmosphere Substances 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
150000007513 acids Chemical class 0.000 description 9
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
239000003795 chemical substances by application Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 7
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
208000012661 Dyskinesia Diseases 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 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 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
229960003878 haloperidol Drugs 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
230000035939 shock Effects 0.000 description 6
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
125000005907 alkyl ester group Chemical group 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 5
229960004170 clozapine Drugs 0.000 description 5
230000000142 dyskinetic effect Effects 0.000 description 5
UVNXNSUKKOLFBM-UHFFFAOYSA-N imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=CSC2=NC=CN21 UVNXNSUKKOLFBM-UHFFFAOYSA-N 0.000 description 5
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
239000002904 solvent Substances 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
208000009132 Catalepsy Diseases 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
206010039424 Salivary hypersecretion Diseases 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
206010047853 Waxy flexibility Diseases 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
239000008101 lactose Substances 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
239000011976 maleic acid Substances 0.000 description 4
230000036544 posture Effects 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
230000004044 response Effects 0.000 description 4
239000011734 sodium Substances 0.000 description 4
239000008107 starch Substances 0.000 description 4
150000003462 sulfoxides Chemical class 0.000 description 4
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
208000019901 Anxiety disease Diseases 0.000 description 3
KLYCPFXDDDMZNQ-UHFFFAOYSA-N Benzyne Chemical compound C1=CC#CC=C1 KLYCPFXDDDMZNQ-UHFFFAOYSA-N 0.000 description 3
206010015995 Eyelid ptosis Diseases 0.000 description 3
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 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
230000016571 aggressive behavior Effects 0.000 description 3
230000036506 anxiety Effects 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000000284 extract Substances 0.000 description 3
GHDPOJZBSAMLHV-UHFFFAOYSA-N imidazo[2,1-b][1,3,5]benzothiadiazepine Chemical compound C1=NC2=CC=CC=C2SC2=NC=CN21 GHDPOJZBSAMLHV-UHFFFAOYSA-N 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
201000003004 ptosis Diseases 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
150000003457 sulfones Chemical class 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
238000012360 testing method Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
HFOQUQYLMFQVEU-UHFFFAOYSA-N 1,3,5-benzothiadiazepine Chemical compound S1C=NC=NC2=CC=CC=C12 HFOQUQYLMFQVEU-UHFFFAOYSA-N 0.000 description 2
JTPVTUYFSZKBFJ-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfanyl)aniline Chemical compound NC1=CC=CC=C1SC1=NC=CN1 JTPVTUYFSZKBFJ-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
206010060860 Neurological symptom Diseases 0.000 description 2
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
206010044565 Tremor Diseases 0.000 description 2
239000013543 active substance Substances 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
150000003973 alkyl amines Chemical class 0.000 description 2
125000005115 alkyl carbamoyl group Chemical group 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
230000000561 anti-psychotic effect Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
238000009835 boiling Methods 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
230000000632 dystonic effect Effects 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
229910052987 metal hydride Inorganic materials 0.000 description 2
150000004681 metal hydrides Chemical class 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
150000004967 organic peroxy acids Chemical class 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
150000004965 peroxy acids Chemical class 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000006798 ring closing metathesis reaction Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
210000003625 skull Anatomy 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000011343 solid material Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
238000005303 weighing Methods 0.000 description 2
VVNCUDFIJWCVHI-BTJKTKAUSA-N (z)-but-2-enedioic acid;5-(4-methylpiperazin-1-yl)imidazo[2,1-b][1,3,5]benzothiadiazepine Chemical compound OC(=O)\C=C/C(O)=O.C1CN(C)CCN1C1=NC2=CC=CC=C2SC2=NC=CN12 VVNCUDFIJWCVHI-BTJKTKAUSA-N 0.000 description 1
YWJUVNPYPVOJPC-BTJKTKAUSA-N 1,2,3-benzothiadiazepine;(z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.S1N=NC=CC2=CC=CC=C12 YWJUVNPYPVOJPC-BTJKTKAUSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
XFNJYAKDBJUJAJ-UHFFFAOYSA-N 1,2-dibromopropane Chemical compound CC(Br)CBr XFNJYAKDBJUJAJ-UHFFFAOYSA-N 0.000 description 1
ORPVVAKYSXQCJI-UHFFFAOYSA-N 1-bromo-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Br ORPVVAKYSXQCJI-UHFFFAOYSA-N 0.000 description 1
FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
CPGITOBGMRTSMN-UHFFFAOYSA-N 1lambda4,2,3-benzothiadiazepine 1-oxide Chemical compound O=S1N=NC=CC2=CC=CC=C12 CPGITOBGMRTSMN-UHFFFAOYSA-N 0.000 description 1
QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
FILREWYTDPRLQT-UHFFFAOYSA-N 2-(2-nitrophenyl)sulfanyl-1h-imidazole Chemical compound [O-][N+](=O)C1=CC=CC=C1SC1=NC=CN1 FILREWYTDPRLQT-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
IRJQLJNSZHGTFA-UHFFFAOYSA-N 2h-imidazo[4,5-i][1,2,3]benzothiadiazepine Chemical class C1=CC2=CC=NNSC2=C2C1=NC=N2 IRJQLJNSZHGTFA-UHFFFAOYSA-N 0.000 description 1
QDWTXRWOKORYQH-UHFFFAOYSA-N 3-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC(Br)=C1 QDWTXRWOKORYQH-UHFFFAOYSA-N 0.000 description 1
SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 1
MICKCJZTFKUVGO-UHFFFAOYSA-N 5-bromo-5-nitrocyclohexa-1,3-diene Chemical class [O-][N+](=O)C1(Br)CC=CC=C1 MICKCJZTFKUVGO-UHFFFAOYSA-N 0.000 description 1
NLIJIXLRIYPOHM-UHFFFAOYSA-N 5-methylsulfanyl-1h-imidazole Chemical compound CSC1=CN=CN1 NLIJIXLRIYPOHM-UHFFFAOYSA-N 0.000 description 1
ZPLWZRFPFJQCRZ-UHFFFAOYSA-N 5-methylsulfanylimidazo[2,1-b][1,3,5]benzothiadiazepine;hydrochloride Chemical compound Cl.CSC1=NC2=CC=CC=C2SC2=NC=CN12 ZPLWZRFPFJQCRZ-UHFFFAOYSA-N 0.000 description 1
JXYMUUNNALFNOK-UHFFFAOYSA-N 6h-imidazo[2,1-b][1,3,5]benzothiadiazepine-5-thione Chemical compound S=C1NC2=CC=CC=C2SC2=NC=CN12 JXYMUUNNALFNOK-UHFFFAOYSA-N 0.000 description 1
ZHKNVMCHPSGJPD-UHFFFAOYSA-N 8-methoxy-5-methylsulfanylimidazo[2,1-b][1,3,5]benzothiadiazepine Chemical compound CSC1=NC2=CC(OC)=CC=C2SC2=NC=CN21 ZHKNVMCHPSGJPD-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
MHJAQLFATQOIJV-UHFFFAOYSA-N Br.S1(C=NC=NC2=C1C=CC=C2)(=O)=O Chemical compound Br.S1(C=NC=NC2=C1C=CC=C2)(=O)=O MHJAQLFATQOIJV-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
NQBLPNXIMRCZNW-UHFFFAOYSA-N Cl.Cl.S1C=NC=NC2=C1C=CC=C2 Chemical compound Cl.Cl.S1C=NC=NC2=C1C=CC=C2 NQBLPNXIMRCZNW-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
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 1
239000004471 Glycine Substances 0.000 description 1
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
208000016285 Movement disease Diseases 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
206010038743 Restlessness Diseases 0.000 description 1
NKEGQPANSFWNER-UHFFFAOYSA-N S1(C=NC=NC2=C1C=CC=C2)(=O)=O Chemical compound S1(C=NC=NC2=C1C=CC=C2)(=O)=O NKEGQPANSFWNER-UHFFFAOYSA-N 0.000 description 1
241000282695 Saimiri Species 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
239000011149 active material Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000003463 adsorbent Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
238000013019 agitation Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
229910000272 alkali metal oxide Inorganic materials 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
125000005037 alkyl phenyl group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000007900 aqueous suspension Substances 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
239000012298 atmosphere Substances 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
230000006399 behavior Effects 0.000 description 1
230000008901 benefit Effects 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
BEZLSTDRWMDCLB-UHFFFAOYSA-N benzyl 4-(1-oxidoimidazo[2,1-b][1,3,5]benzothiadiazepin-1-ium-5-yl)piperazine-1-carboxylate Chemical compound [O-][N+]=1C=CN2C=1SC1=CC=CC=C1N=C2N(CC1)CCN1C(=O)OCC1=CC=CC=C1 BEZLSTDRWMDCLB-UHFFFAOYSA-N 0.000 description 1
YKMBRJSYBRZEFA-UHFFFAOYSA-N benzyl 4-imidazo[2,1-b][1,3,5]benzothiadiazepin-5-ylpiperazine-1-carboxylate Chemical compound C1CN(C=2N3C=CN=C3SC3=CC=CC=C3N=2)CCN1C(=O)OCC1=CC=CC=C1 YKMBRJSYBRZEFA-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
230000001143 conditioned effect Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
229940099112 cornstarch Drugs 0.000 description 1
150000003983 crown ethers Chemical class 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
238000001514 detection method Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical compound O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
FWGKRIIALYHPBW-UHFFFAOYSA-N ethyl 4-imidazo[2,1-b][1,3,5]benzothiadiazepin-5-ylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C1=NC2=CC=CC=C2SC2=NC=CN12 FWGKRIIALYHPBW-UHFFFAOYSA-N 0.000 description 1
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
238000011049 filling Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
239000008187 granular material Substances 0.000 description 1
125000004997 halocarbonyl group Chemical group 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
210000003128 head Anatomy 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
XPDNQJSMDJXYSG-UHFFFAOYSA-N imidazo[2,1-b][1,3,5]benzothiadiazepin-5-yl thiocyanate Chemical compound N#CSC1=NC2=CC=CC=C2SC2=NC=CN12 XPDNQJSMDJXYSG-UHFFFAOYSA-N 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
238000011835 investigation Methods 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000006166 lysate Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000002736 metal compounds Chemical class 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
238000001465 metallisation Methods 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
238000010984 neurological examination Methods 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
229910017464 nitrogen compound Inorganic materials 0.000 description 1
150000002830 nitrogen compounds Chemical group 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006072 paste Substances 0.000 description 1
FACMWMBWGSPRKO-UHFFFAOYSA-N pentiapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2SC2=NC=CN12 FACMWMBWGSPRKO-UHFFFAOYSA-N 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical class OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
229940116357 potassium thiocyanate Drugs 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
210000001747 pupil Anatomy 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000008213 purified water Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000007142 ring opening reaction Methods 0.000 description 1
208000026451 salivation Diseases 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
238000000935 solvent evaporation Methods 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
230000001180 sulfating effect Effects 0.000 description 1
150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
238000010998 test method Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Polymerisation Methods In General (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

DD81230728A 1980-06-12 1981-06-11 Verfahren zur herstellung neuer imidazobenzothiadiazepinen DD160535A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US15867180A	1980-06-12	1980-06-12

Publications (1)

Publication Number	Publication Date
DD160535A5 true DD160535A5 (de)	1983-09-07

Family

ID=22569177

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD81230728A DD160535A5 (de)	1980-06-12	1981-06-11	Verfahren zur herstellung neuer imidazobenzothiadiazepinen

Country Status (20)

Country	Link
EP (1)	EP0042354B1 (da)
JP (1)	JPS57118589A (da)
KR (2)	KR840002145B1 (da)
AT (1)	ATE16935T1 (da)
AU (1)	AU538864B2 (da)
CA (1)	CA1163630A (da)
DD (1)	DD160535A5 (da)
DE (1)	DE3173184D1 (da)
DK (1)	DK255281A (da)
ES (2)	ES8300761A1 (da)
FI (1)	FI69310C (da)
GB (1)	GB2077727B (da)
GR (1)	GR78222B (da)
HU (1)	HU185128B (da)
IE (1)	IE52043B1 (da)
IL (1)	IL63079A (da)
NO (1)	NO811977L (da)
NZ (1)	NZ197392A (da)
PT (1)	PT73173B (da)
ZA (1)	ZA813930B (da)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FI824170A7 (fi) *	1981-12-07	1983-06-08	Ciba Geigy Ag	Imidatsobensodiatsepiinit, menetelmä niiden valmistamiseksi, näitä yhdisteitä sisältävät farmaseuttiset valvalmisteet ja niiden terapeuttinen käyttö.
US4460587A (en) *	1981-12-07	1984-07-17	Ciba-Geigy Corporation	5-Diazacycloalkyl imidazo[1,2-c][1,3]benzodiazepines
US4459232A (en) *	1981-12-07	1984-07-10	Ciba-Geigy Corporation	Imidazo[1,2-c][1,3]benzodiazepines
US4507311A (en) *	1981-12-07	1985-03-26	Ciba-Geigy Corporation	Imidazo[1,2-c][1,3]benzodiazepines
US4460508A (en) *	1981-12-07	1984-07-17	Ciba-Geigy Corporation	5-Diazacycloalkylimidazo[1,2-c][1,3]benzodiazepines
US4595535A (en) *	1983-06-06	1986-06-17	Ciba-Geigy Corporation	Diazacycloalkyl-1,2,4-triazolo[2,3-c][1,3]benzodiazepines useful as neuroleptic and/or antihistaminic agents

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2349064A1 (de) *	1973-09-29	1975-04-10	Basf Ag	1,3-diazacycloalkeno- eckige klammer auf 1,2-d eckige klammer zu -benzo- eckige klammer auf f eckige klammer zu -1,3,4- thiadiazepine
IT7851496A0 (it) *	1977-10-31	1978-10-13	Sandoz Ag	Menti pirazinobenzossazepine loro preparazione e loro impiego quali medica

1981
- 1981-05-30 JP JP56083705A patent/JPS57118589A/ja active Pending
- 1981-06-08 FI FI811771A patent/FI69310C/fi not_active IP Right Cessation
- 1981-06-09 GB GB8117623A patent/GB2077727B/en not_active Expired
- 1981-06-09 AT AT81810228T patent/ATE16935T1/de not_active IP Right Cessation
- 1981-06-09 DE DE8181810228T patent/DE3173184D1/de not_active Expired
- 1981-06-09 EP EP81810228A patent/EP0042354B1/de not_active Expired
- 1981-06-10 GR GR65189A patent/GR78222B/el unknown
- 1981-06-10 CA CA000379490A patent/CA1163630A/en not_active Expired
- 1981-06-11 DK DK255281A patent/DK255281A/da not_active Application Discontinuation
- 1981-06-11 PT PT73173A patent/PT73173B/pt unknown
- 1981-06-11 ES ES502949A patent/ES8300761A1/es not_active Expired
- 1981-06-11 IE IE1302/81A patent/IE52043B1/en unknown
- 1981-06-11 ZA ZA813930A patent/ZA813930B/xx unknown
- 1981-06-11 NO NO811977A patent/NO811977L/no unknown
- 1981-06-11 HU HU811736A patent/HU185128B/hu unknown
- 1981-06-11 IL IL63079A patent/IL63079A/xx unknown
- 1981-06-11 AU AU71641/81A patent/AU538864B2/en not_active Ceased
- 1981-06-11 NZ NZ197392A patent/NZ197392A/en unknown
- 1981-06-11 DD DD81230728A patent/DD160535A5/de unknown
- 1981-06-12 KR KR1019810002117A patent/KR840002145B1/ko not_active Expired
1982
- 1982-07-01 ES ES513638A patent/ES8304570A1/es not_active Expired
1984
- 1984-07-26 KR KR1019840004435A patent/KR850000614B1/ko not_active Expired

Also Published As

Publication number	Publication date
AU7164181A (en)	1981-12-17
IL63079A0 (en)	1981-09-13
ZA813930B (en)	1982-06-30
EP0042354B1 (de)	1985-12-11
KR830006313A (ko)	1983-09-20
PT73173A (de)	1981-07-01
GB2077727A (en)	1981-12-23
GR78222B (da)	1984-09-26
ES502949A0 (es)	1982-11-01
ATE16935T1 (de)	1985-12-15
CA1163630A (en)	1984-03-13
DK255281A (da)	1981-12-13
EP0042354A3 (en)	1982-02-24
IL63079A (en)	1985-06-30
KR850001467A (ko)	1985-03-18
PT73173B (de)	1983-04-29
KR840002145B1 (ko)	1984-11-23
DE3173184D1 (en)	1986-01-23
ES8300761A1 (es)	1982-11-01
ES8304570A1 (es)	1983-05-16
FI69310B (fi)	1985-09-30
ES513638A0 (es)	1983-03-01
AU538864B2 (en)	1984-08-30
NZ197392A (en)	1984-03-30
IE52043B1 (en)	1987-05-27
GB2077727B (en)	1984-03-07
HU185128B (en)	1984-12-28
FI811771L (fi)	1981-12-13
IE811302L (en)	1981-12-12
JPS57118589A (en)	1982-07-23
EP0042354A2 (de)	1981-12-23
NO811977L (no)	1981-12-14
FI69310C (fi)	1986-01-10
KR850000614B1 (ko)	1985-05-01

Publication	Publication Date	Title
DE69000467T2 (de)	1993-04-01	Bis-aza-bicyclische anxiolytica und antidepressiva.
DE2915318A1 (de)	1979-10-31	Cycloalkyltriazole, verfahren zu ihrer herstellung und diese enthaltende arzneimittel
EP0163260B1 (de)	1988-08-03	Neue substituierte Pyrrolidinone, Verfahren zu ihrer Herstellung und Arzneimittel
DE1965264A1 (de)	1970-07-16	Pyrazinoylsulfamide und Verfahren zu ihrer Herstellung
EP0058341A1 (de)	1982-08-25	Azepinderivate, ihre Herstellung und diese enthaltende Arzneimittel
DE3343922A1 (de)	1984-06-28	Gewisse substituierte pyrazolochinoline, verfahren zu ihrer herstellung, pharmazeutische praeparate enthaltend diese verbindungen und ihre therapeutische anwendung
EP1296986A1 (de)	2003-04-02	5-aminoalkyl-pyrazolo[4,3-d]pyrimidine mit phosphodiesterase v inhibierender wirkung
DD160535A5 (de)	1983-09-07	Verfahren zur herstellung neuer imidazobenzothiadiazepinen
US4444688A (en)	1984-04-24	Imidazobenzothiadiazepines
DD150602A5 (de)	1981-09-09	Verfahren zur herstellung 6-substituierter 11-alkylen-morphantridine
DE3115552A1 (de)	1982-02-18	4,1-benzoxazepine und diese verbindungen enthaltende arzneimittel
EP0461574B1 (de)	1997-09-24	3,7-Diazabicyclo(3,3,1)-nonan-Verbindungen enthaltende Arzneimittel
DE2601262A1 (de)	1976-07-22	1-r-4-(omega-substituierte alkyl)-3, 3-diphenyl-2-pyrrolidinone und verfahren zu ihrer herstellung
DE69617001T2 (de)	2002-07-11	(2-morpholinylmethyl)benzamid-derivate
DE69106516T2 (de)	1995-05-11	Pyridopyrazinderivate zur behandlung von drogenmissbrauch und -sucht.
EP0124630B1 (de)	1987-01-28	Pyrimidin-Thioalkylpyridin-Derivate, Verfahren zu ihrer Herstellung und diese Verbindung enthaltende Arzneimittel
DE2719607A1 (de)	1977-11-17	Benzodiazepine, verfahren zu ihrer herstellung und sie enthaltende arzneimittel
DE69303798T2 (de)	1996-11-28	Benz[e]inden Derivate, Verfahren zu ihrer Herstellung sowie diese enthaltende Arzneimittel und ihre Verwendung
US4391808A (en)	1983-07-05	5(1-Piperazinyl(imidazo[2,1-b][1,3,5]benzothiadiazepines
EP0081461A2 (de)	1983-06-15	Imidazobenzodiazepine, Verfahren zu ihrer Herstellung, pharmazeutische Präparate enthaltend diese Verbindungen, sowie ihre therapeutische Verwendung
EP0086980B1 (de)	1986-01-02	Substituierte Dibenzodiazepinone, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
EP0129509B1 (de)	1989-08-23	Triazol(2,3-c)(1,3)benzodiazepine, Verfahren zu ihrer Herstellung, pharmazeutische Präparate enthaltend diese Verbindungen, sowie ihre therapeutische Verwendung
CH615681A5 (da)	1980-02-15
DE2609574A1 (de)	1976-09-23	Monosubstituiertes piperazinderivat, verfahren zu seiner herstellung und es enthaltende arzneimittel
US4477379A (en)	1984-10-16	Imidazobenzothiadiazepines