PL92568B1 - 1,4-benzodiazepine derivs - with alkylsulphon(in)ylalkyl substituent in 1-position[DE2166472A1] - Google Patents
1,4-benzodiazepine derivs - with alkylsulphon(in)ylalkyl substituent in 1-position[DE2166472A1] Download PDFInfo
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- PL92568B1 PL92568B1 PL18373971A PL18373971A PL92568B1 PL 92568 B1 PL92568 B1 PL 92568B1 PL 18373971 A PL18373971 A PL 18373971A PL 18373971 A PL18373971 A PL 18373971A PL 92568 B1 PL92568 B1 PL 92568B1
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- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- ARAFEULRMHFMDE-UHFFFAOYSA-N 1,3-oxazolidine-2,5-dione Chemical compound O=C1CNC(=O)O1 ARAFEULRMHFMDE-UHFFFAOYSA-N 0.000 claims abstract 3
- 150000002576 ketones Chemical class 0.000 claims abstract 3
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 2
- -1 alkoxy radical Chemical class 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 5
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims description 3
- GSEZYWGNEACOIW-UHFFFAOYSA-N bis(2-aminophenyl)methanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1N GSEZYWGNEACOIW-UHFFFAOYSA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 229920000137 polyphosphoric acid Polymers 0.000 claims 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 claims 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims 2
- 150000001478 2,5-oxazolidinediones Chemical class 0.000 claims 1
- 239000006184 cosolvent Substances 0.000 claims 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims 1
- 239000012046 mixed solvent Substances 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 abstract description 3
- 150000002367 halogens Chemical class 0.000 abstract description 3
- 150000007513 acids Chemical class 0.000 abstract description 2
- 230000000147 hypnotic effect Effects 0.000 abstract description 2
- 239000000932 sedative agent Substances 0.000 abstract description 2
- 230000002048 spasmolytic effect Effects 0.000 abstract description 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 239000003326 hypnotic agent Substances 0.000 abstract 1
- 229940035363 muscle relaxants Drugs 0.000 abstract 1
- 239000003158 myorelaxant agent Substances 0.000 abstract 1
- 150000007524 organic acids Chemical class 0.000 abstract 1
- 229940125723 sedative agent Drugs 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 5
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- VOLGAXAGEUPBDM-UHFFFAOYSA-N $l^{1}-oxidanylethane Chemical compound CC[O] VOLGAXAGEUPBDM-UHFFFAOYSA-N 0.000 description 1
- ZHYMGSPDEVXULU-UHFFFAOYSA-N 1,2-benzodiazepin-3-one Chemical compound N1=NC(=O)C=CC2=CC=CC=C21 ZHYMGSPDEVXULU-UHFFFAOYSA-N 0.000 description 1
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical compound [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- AZRRZGIBBLWSSQ-UHFFFAOYSA-N 4-ethyl-7-phenyl-3,5-diazabicyclo[2.2.2]octane-2,6-dione Chemical class N1C(=O)C2C(=O)NC1(CC)CC2C1=CC=CC=C1 AZRRZGIBBLWSSQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/26—Preparation from compounds already containing the benzodiazepine skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/28—Preparation including building-up the benzodiazepine skeleton from compounds containing no hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/30—Preparation including building-up the benzodiazepine skeleton from compounds already containing hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/30—Preparation including building-up the benzodiazepine skeleton from compounds already containing hetero rings
- C07D243/36—Preparation including building-up the benzodiazepine skeleton from compounds already containing hetero rings containing an indole or hydrogenated indole ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Przedmiotem wynalazku jesit sposób wytwarza¬ nia nowych pochodnych benzodwuazepiny, podsta¬ wionych w pozycji 1, o wzorze 1, w którym Ri oznacza atom wodoru, chlorowca, grupe nitrowa, cyjanowa, nizszy rodnik alkoksylowy lub rodnik trójfluoroimetyiowy, R2 oznacza grupe pirydylowa lub grupe o wzorze 2, w którym R5 i R6 oznacza¬ ja niezaleznie od siebie atom wodoru, chlorowca, nizszy rodnik alkilowy o 1—2 atomach wegla lub rodnik trógiflluorometylowy, R8 oznacza atom wo¬ doru lub nizszy rodnik alkilowy o 1—4 atomach wegla, R4 oznacza nizszy rodnik alkilowy o 1—4 atomach wegla, rodnik cykloalkilowy o 3—6 ato¬ mach wegla, rodnik cykloalkiloalkilowy,''w którym czesc cykioailkilowa zawiera 3—6 atomów wegla, a czesc alkilowa 1—4 atomów weglla, rodnik arylo- wy lub rodnik aryloalkiiowy, m jest równe 1 lub 2, a n jest liczba calkowita 2—4 oraz ich soli.W zwiazkach o wzorze ogólnym 1 atom chlorow¬ ca moze oznaczac atom fluoru, chloru, bromu lufo jodu; rodnik alkilowy moze miec lancuch prosty lufo rozgaleziony; nizszy rodnik alkilowy moze na przyklad oznaczac rodnik metylowy, etylowy, n- -prcpylowy, izopropyllowy, n-butyilowy i HIrzed". -butylowy; nizszy rodnik alkoksylowy moze ozna¬ czac na przyklad rodnik metoksylowy, efcoksylowy, n-propoksylowy, izopropoksylowy, n4)utoksylowy (i III rzed. butoksylowy; rodindk cykloalkilowy moze oznaczac na przyklad rodnik cyklopropylowy, cy- klioibaitylowy, cyfcloheksylowy i cyklopentylowy; 2 rodnik cyfcloalkiloalkilowy moze oznaczac na przyklad rodnik cyklopropylometylowy, cykio- foutylometylowy, cyklopentyflometylowy, cyklohek- syilometylowy, i cykloheksyloetylowy; rodnik afry- lowy moze oznaczac na przyklad rodnik fenylowy, jedno- lub dwiupodstawiony rodnik fenylowy, w któ¬ rym podstawnikami w pierscieniu fenylowym moga byc atomy chlorowca, takie jak aiotm chloru, fluoru, bromu lub jcdu, nizszy rodnik alkilowy, taki jak metylowy lub etylowy, nizszy rodnik alkoksylowy* taki jak metoksylowy lub etoksylowy, grupa nitro¬ wa i rodnik trójtfauoirometylowy; rodnik aryloalki¬ iowy imoze oznaczac na przyklad rodnik benzylowy i fenyloetylowy; rodnik alkenyIowy —CnH^ — mo¬ ze byc rodnikiem alkenylwoym o prostym lub roz¬ galezionym lancuchu o 2—4 atomach wejgla, na przyklad takim, jak rodnik etylenowy, 1-metyloety- lenowy, 2nmetyloetylenowy, trójmetylenowy, 1-me¬ tylotrójmetylenowy i 2-metylotir6jmetylenowy.Pochodne benzodwuazepiny o wzorze 1, podsta¬ wione w pozycji 1 oraz ich sole sa zwiazkami no- wytmi. Nieoczekiwanie stwierdzono, ze zwiazki te, a szczególnie zwiazkli o wzorze ogólnym la, w któ¬ rym Rj, R4, R5, R6 i m maja znaczenie podane po¬ wyzej, a n' jest równe 2 lufo 3 oraz ich dopusz¬ czalne farmaceutycznie sole z kwasami nieorgani¬ cznymi i organicznym^ maja cenne wlasciwoscl farmakologiczne, szczególnie uspakajajace, rozluz¬ niajace miesnie, spazmolityCzne i nasenne. 9256892568 Sposób wytwarzania nowych pochodnych foenzo- dwuazepiny o wzorze 1 wedlug wynalazku polega na reakcji pochodnej aminofenyloketonu o wzo¬ rze 3, w kit6rym Rlt R2, R4, n i ni maja znaczenie podane powyzej z 2,5-oksaizOlidynodionem o wzo¬ rze 4, w którym R, ma znaczenie podane powy¬ zej. Reakcje prowadzi sie w obecnosci rozpusz¬ czalnika lub mieszaniny rozpuszczalników. Odpo¬ wiednim rozpuszczalnikiem jest na przyklad chlo¬ roform, czterochlorek wegla, chlorek metylenu, chlorek etylenu, eter etylowy, eter izopropylowy, czterowodorotfuran, dioksan, woda, metanol, eta¬ nol, dwumetyloformamid1, dwumetylosulfotlenek lufo ich mieszaniny. Reakcje prowadzi sie zwykle w obecptfosc4JnTOi^,*5p'^ czy™ jako kwasy stosu¬ je si^ chlorowodór, tJrofhowodór, kwas siarkowy, kwas* fosforowy, kwasy polifosforowe, trójchlorek borowy ^ kn^Vp*toljai^ Reakcje pro¬ wadzic7^ gal^^ —8® — +il20°C, a korzystniej w (temperaturze 0—30°C. Temperatu¬ re nizsza i wyzsza od tego zakresu mozna równiez stosowac, ale jest to mniej korzystne. W wiek¬ szosci wypadków reakcje prowadzi sie w tempe¬ raturze pokojowej lufo ponizej. Cisnienie nie ma istotnego znaczenia i reakcje mozna prowadzic pod cisnieniem atmosferycznym, pod zmniejszonym lub zwiekszonym cisnieniem. W razie potrzeby, pro¬ ces mozna prowadzic w atmosferze gazu obojetne¬ go takiego jak azot, argon itp.Stosunek molowy pochodnej i2,5^ionu do ketonu aminofenylowego nie jest istotny, ale korzystnie stosuje sie przynajmniej stechiometryczne ilosci reagentów. Przewaznie korzystne jest zastosowanie nadmiaru pochodnej 2,5-dionu. W razie potrzeby, reagenty mozna ogrzewac w odpowiednim rozpusz¬ czalniku, takim jak dwumetylosulfotlenek, dwuime- tylofonmamid i podobne do czasu zakonczenia re¬ akcji.Sposobem wedlug wynalazku otrzymuje sde na przyklad nastepujace zwiazki: l-/p-nietylosu(lfonyloety;lo/-5-fenylo-7-chloro-l,3- Hdwuwodoro-2H-l,4Hbenzodwuazepinon-2 1-/p-metylosulfonyioetylo/-5-fenylO-7-cyjano-l ,3- -dwuwodoro-2H-l,4^benzodwuazepliinon-2 1-/^Hmetylosulfonyloetylo/-5-fenylo-7-nitro-1,3- dwu- wodoro-2H-l,4-benzod!wuazepinon-2 lVP-metylosulfonyloetylo/-5-fenylo-7-metoksylo- -1,3-dwuwodoTo-2H-i,4^benzodwuazepinon-2 l-/p-metylo&uliConytloietylo/-5-fenylo -7- trójifluorome- tylo-l,3-dwuwOdoro»2H-i,4-Jbenzodwuazepinon-2 1- /0-metylosuflfonyloetylo /-5-fenylo-7-foromo-l,3- -dwuwodóro-2H-il ,4-foenzodwuazepinon-2 1-/p-metyiLosulfonyloetylo /-5-fenylo-1,3-dWuwodoro- -2Hh1 ,4-foenzodwuazepinon-2 1-ypnmetylosulfonyloetylo /-3-metylo-5-fenylo-7-chlo¬ rowi^-dwuwodoro-2H-il,4-foenzodwuazepinon-2 1-yp-metylosulfonyloetylo/-5-/2'-pirydylo/-7-cMoro- A ,3-dwuwodoa*o-2H-l ,4-foenzodwuazepinon-2 -l/j3-metylosulfonyloetylcV-5-/o-fluorofenylo/-7-cnlo- ro-1,3-dwuwodoro-2!H-i,4-foenzodwuazejpinon-2 l-/p-metylosulfonyloetylo/-5-/2'-pa'ryd54o /-74romo - -1,3-dwuwodoro-2iH-1,4-foenzodwuazepinon-2 1-/p-metylosulfonyioetylo/-5-/0-chlorofenylo /-7^chio- ro-l,3-dwuwodoro-2H-l,4-foenzodlwuazepinon-2 iH/p^metylosulfc^y-itoliilo/-7^chloro-l,3- -dwuwodQro-2JH-l,4-benzodwuazepinon^a l-/p-metylosulfonyloetylo,/ -5- / o-chlórofenylóA-7Hna- troni,3Hdwuwodoro-2H-l,4^benzodwuazepinon-2 1- / ipnmetylosulfonylloetylo / -5- / o-tró|j^luorametylo- fenylo / -7-chloro-ly3^dwulwodoro-2HJl,4-foenzodwu- azeplinon-2 l-^P-^ylosulMonyloetya'0/H5Hfenylo-7^hloTO-l^-dwu- wodoro-2iH-l ,4-(benzodwuazepinonH2 i -/{J-etylosulfonyloetyilaZ-iS^enyllo^-cyljano-i,3-tiwu- wodoro-2H-d,4-foenzodwuazepinonH2 1H/j3-etylosuilfonyloetylo/-5-fenyilo-7-nitfo-l,3-dwuwo- doro-2H-l ,4-ibenzódwuazejpinon-2 1- /0-etylosulfonyloetylo / -5-fenylo-7-trójfluotrome- 'tylo-il,3-dwuwodoro-2H-il,4-toenzodwuazepinon-2 l-/p-etylosulfonyloetylo / -5-fenylo-7-foromo-il,3-dwu- wodoro-2H-l,4-benzodwuazepincn-2 l-ZP-etylosulfonyloetylo /-5- /o-fluorofenylo /-7-chlo- ro-il ,3-diwuwodoro-2iH-l ,4-fbenzodwuazepinon-2 l-/p-etylosulfonyloetylo/-5-./2/-pirydylo/-74)romo-l,3- -dwuwiodoro-2H-l,4-foenzodwuazepinon-2 1n/fl-etylosullfonylloetylo/H5^0Hchiorofenylo/-7-chlo- ro-1,3-dwuwod oro-2H-d,4-foenzodwuazepinon-2 l-!/^-etylosuilfonyloetylo/-l5-/o^toliil:o/H7-chloro-l^- -dwuwodoro-2H-l,4-(benzodwuazepinon-2 l-/p-etylosuilfonyloetytlo/-6-/o-chlorofenylo/-7Hnitro- % -ii ^-dwuwoidiOiro-BH-l ,4-foenzodwuazepiinon-2 1- / ip-propyOosulfonyloetyllo / -5-fenylo-7-chloro-l,3- -dwuwodoro-2H-l,4-ibenzadwuazepinon-2 1- / j3-propylosuQfonyloetylo / -finfenyllo / -7-nitro-l,3- -dwuwodoro-2H-l,4-benzodwuazepinon-2 1- / j3-tizopropylosulfonyloetylo / -5- / o-chlorofenylo / -7-chiloro-l,3-dwuwod0T0-2H-1,4-foenzodwuazepinon- -2 1- / P-izopropylosulfonyloetylo/ -5- / o-todilo /-7-chlo- ro-l,3-dwuwodor0-2H-1,4-foenzodwuazepinon-2 1- / 0-izopropyHosulfonyloetyllo / -5- / onchlorofenylo / -7Hnitro-l,3-dwuwodoro^2iH-i,4-foenzodwuazepinon-2 i^Y-m^yi^iulfanyi°Pr
Claims (10)
- Zastrzezenia patentowe 10 15 1. Sposób wytwarzania nowych pochodnych ben- zodwuazepdny o wzorze 1, w którymi Ri oznacza atom wodoru, atom chlorowca, grupe niltrowa, gru¬ pe cyjanowa, nizszy rodnik alkoksylowy, lub rodnik trójfluorometylowy, Rf oznacza grupe pirydylowa lub grupe o wzorze 2, w którym R6 i R6 oznaczaja niezaleznie od siebie atom wodoru, atom chlorowca, nizszy rodnik alkilowy o 1—2 atomach wegla lub rodnik trójfluorometylowy. R3 oznacza atom wodoru lub nizszy rodnik alkilowy o 1—4 atomach wegla, R4 oznacza rodnik cytoloalkilowy o 3—6 atomach wegla, rodnik cyfcloalkiloalkilowy, w którym czesc cykloalkilowa zawiera 3—6 atomów wegla, a czesc alkilowa 1—4 atomów wegla, rodnik aryiowy -lulb rodnik aryloalkilowy, m jest równe 1 lub 2, a n jest liczba calkowita 2—4 oraz ich soli, znamienny tym, ze pochodna aiminofenyloketonu o wzorze 3, w któ¬ rym Ri, R2, R4, m i n maja znaczenie podane po¬ wyzej poddaje sie reakcji z 2,5-oksazolidynodionem o wzorze 4, w którym R8 ma znaczenie podane po¬ wyzej.
- 2. Sposób wedlug zastrz. 1, znamienny tym, ze re¬ akcje prowadzi sie w rozpuszczalniku lub mieszani¬ nie rozpuszczalników i ewentualnie w obecnosci kwasu. 35
- 3. Sposób wedlug zastrz. 2, znamienny tym, ze ja¬ ko kwas stosuje sie chlorowodór, bramowodór, kwas siarkowy, kwas fosforowy, kwas polifosforowy, trój- fluorek borowy lufo kwas p-toluenosulfonowy.
- 4. Sposób wedlug zastrz. 2, znamienny tym, ze ja- *o ko rozpuszczalnik stosuje sie chloroform, cztero¬ chlorek wegla, chloTek metylenu, chlorek etylenu, eter etylowy, eter izopropylowy, czterowodorofuran. 30 dioksan, wode, metanol, etanol,' dwumetyloformaimid lub dwumetylosulfotlenek.
- 5. Sposób wedlug zastrz. 2, znamienny tym, ze reakcje prowadzi sie w temperaturze -^25 +120°C.
- 6. Sposób wedlug zastrz. 2, znamienny tym, ze re¬ akcje prowadzi sie w temperaturze 0—30°C.
- 7. Sposób wedlug zastrz. 2, znamienny tym, ze stosuje sie przynajmniej 1 mol pochodnej 2,5-oksa- zoMdymodionu na 1 mol pochodnej ketami amkiofe- nylowego.
- 8. Sposób wytwarzania nowych pochodnych ben- zodwuazepiny o wzorze 1, w którym Ri oznacza atom wodoru, atom chlorowca, grupe nitrowa, gru¬ pe cyjanowa, mtezy rodnik alkoksylowy lub rod¬ nik trójfluoroimetyiowy, R* oznacza grupe pirydylo¬ wa lub grupe o wzorze 2, w którym R5 i R6 ozna¬ czaja niezaleznie od siebie atom wodoru, atom chlorowca, nizszy rodnik alkilowy o 1—2 atomach wegla lub rodnik trójfluorometylowy. R, oznacza atom wodoru lulb nizszy rodnik alkilowy o 1—4 atomach wegla, R4 oznacza nizszy rodnik alkilo¬ wy o 1—4 atomach wegla, m jeslt równe 1 lub 2, a n jest liczba calkowita 1^4, znamienny tym, ze pochodna aminofienyloketonu o wzorze 3, w 'któ¬ rym Rlf R2, R4, m i n maja znaczenie podane po¬ wyzej poddaje sie reakcji z 2,5-oksazolidynodio¬ nem o wzorze 4, w którym R8 ma znaczenie poda¬ ne powyzej, w rozpuszczalniku lub mieszaninie rozpuszczalników i ewentualnie w obecnosci kwa¬ su, w temperaturze 0—30°C i przy stosunku mo¬ lowym przynajmniej 1 mola pochodnej 2,5-oksazo- lidynodionu na jeden mol pochodnej ketonu aond- nofenylowego.
- 9. Sposób wedlug zastrz. 8, znamienny tym, ze jako kwas stosuje sie chlorowodór, bromowodór, kwas siarkowy, kwas fosforowy, trójfluorek boro¬ wy lub kwas p-toluenosulfonowy.
- 10. Sposób wedlug zastrz. 6, znamienny tym, ze jako rozpuszczalnik stosuje sie chloroform, czte¬ rochlorek wegda, chlorek metylenu, chlorek etyle¬ nu, eter etylowy, czterowodorofuran, wode, meta¬ nol, etanol, dwumetyloformamid, dwumetylosulfo¬ tlenek i ich mieszaniny.92568 CH-R, CnH2n S(0)m-R4 Wzór 1 ch C=N. N-C \ CH, % O Cn,H2rT s(o)m-R4 Wzór 1a Wzór 2 ^\/CO-R2 <\A NH-CnH2n-S(0)m-R4 Wzór 3 R3-CH-C HN—C y v Wzór 4 O Drukarnia Narodowa Zaklad Nr 6, zam. 382/77 Cena 10 zl PL
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1053370A JPS4834600B1 (pl) | 1970-02-05 | 1970-02-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL92568B1 true PL92568B1 (en) | 1977-04-30 |
Family
ID=11752885
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL18373971A PL92568B1 (en) | 1970-02-05 | 1971-02-02 | 1,4-benzodiazepine derivs - with alkylsulphon(in)ylalkyl substituent in 1-position[DE2166472A1] |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS4834600B1 (pl) |
| AT (1) | AT306040B (pl) |
| CH (1) | CH581631A5 (pl) |
| CS (1) | CS179396B2 (pl) |
| DE (1) | DE2166472A1 (pl) |
| PL (1) | PL92568B1 (pl) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5518035U (pl) * | 1978-07-21 | 1980-02-05 | ||
| JPS59112697U (ja) * | 1983-01-20 | 1984-07-30 | 有限会社シオン | 予定表示部材 |
-
1970
- 1970-02-05 JP JP1053370A patent/JPS4834600B1/ja active Pending
-
1971
- 1971-01-28 AT AT352572A patent/AT306040B/de not_active IP Right Cessation
- 1971-02-01 DE DE19712166472 patent/DE2166472A1/de active Pending
- 1971-02-01 CS CS426371A patent/CS179396B2/cs unknown
- 1971-02-01 CH CH1089474A patent/CH581631A5/xx not_active IP Right Cessation
- 1971-02-02 PL PL18373971A patent/PL92568B1/pl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AT306040B (de) | 1973-03-26 |
| CS179396B2 (en) | 1977-10-31 |
| CH581631A5 (pl) | 1976-11-15 |
| JPS4834600B1 (pl) | 1973-10-22 |
| DE2166472A1 (de) | 1974-02-21 |
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