DD266355A5 - Verfahren zur herstellung von neuen 1,4-benzodiozepinen - Google Patents

Verfahren zur herstellung von neuen 1,4-benzodiozepinen Download PDF

Info

Publication number: DD266355A5
Authority: DD; German Democratic Republic
Prior art keywords: formula; compounds; alkyl; methyl; compound
Prior art date: 1986-07-25

Application number

DD87305296A

Other languages

German (de)

English (en)

Inventor

Gerhard Walther

Albrecht Harreus

Karl-Heinz Weber

Werner Stransky

Gojko Muacevic

Stenzel J Casals

Wolf-Dietrich Bechtel

Original Assignee

��@��@��k��

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.)

1986-07-25

Filing date

1987-07-23

Publication date

1989-03-29

1987-07-23 Application filed by ��@��@��k�� filed Critical ��@��@��k��

1989-03-29 Publication of DD266355A5 publication Critical patent/DD266355A5/de

Links

238000000034 method Methods 0.000 title claims description 21
238000002360 preparation method Methods 0.000 title claims description 13
230000008569 process Effects 0.000 title claims description 8
150000001875 compounds Chemical class 0.000 claims abstract description 96
229910052739 hydrogen Inorganic materials 0.000 claims description 26
239000001257 hydrogen Substances 0.000 claims description 25
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
239000000203 mixture Substances 0.000 claims description 22
230000000694 effects Effects 0.000 claims description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 13
150000002367 halogens Chemical class 0.000 claims description 13
229910052757 nitrogen Inorganic materials 0.000 claims description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
230000002776 aggregation Effects 0.000 claims description 10
238000004220 aggregation Methods 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 9
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
229940049706 benzodiazepine Drugs 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 5
230000009471 action Effects 0.000 claims description 5
230000005764 inhibitory process Effects 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
239000005557 antagonist Substances 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
150000001557 benzodiazepines Chemical class 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
230000000144 pharmacologic effect Effects 0.000 claims description 4
230000001624 sedative effect Effects 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 claims description 2
229960004538 alprazolam Drugs 0.000 claims description 2
229910021529 ammonia Inorganic materials 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
239000002243 precursor Substances 0.000 claims description 2
239000000376 reactant Substances 0.000 claims description 2
238000007363 ring formation reaction Methods 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
239000011593 sulfur Substances 0.000 claims description 2
239000003204 tranquilizing agent Substances 0.000 claims description 2
230000002936 tranquilizing effect Effects 0.000 claims description 2
239000002585 base Substances 0.000 claims 4
125000003277 amino group Chemical group 0.000 claims 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
KGKSTPKEAQNJJD-UHFFFAOYSA-N 1-bromo-3-methylpent-1-yn-3-ol Chemical compound CCC(C)(O)C#CBr KGKSTPKEAQNJJD-UHFFFAOYSA-N 0.000 claims 1
SODQFLRLAOALCF-UHFFFAOYSA-N 1lambda3-bromacyclohexa-1,3,5-triene Chemical compound Br1=CC=CC=C1 SODQFLRLAOALCF-UHFFFAOYSA-N 0.000 claims 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
239000003513 alkali Substances 0.000 claims 1
150000001450 anions Chemical class 0.000 claims 1
230000003042 antagnostic effect Effects 0.000 claims 1
125000004122 cyclic group Chemical group 0.000 claims 1
229940079593 drug Drugs 0.000 claims 1
239000003814 drug Substances 0.000 claims 1
150000002431 hydrogen Chemical class 0.000 claims 1
239000000543 intermediate Substances 0.000 claims 1
239000000825 pharmaceutical preparation Substances 0.000 claims 1
125000005543 phthalimide group Chemical class 0.000 claims 1
238000006798 ring closing metathesis reaction Methods 0.000 claims 1
229940125725 tranquilizer Drugs 0.000 claims 1
150000003852 triazoles Chemical class 0.000 claims 1
WZCZNEGTXVXAAS-UHFFFAOYSA-N trifluoromethanol Chemical group OC(F)(F)F WZCZNEGTXVXAAS-UHFFFAOYSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
108010003541 Platelet Activating Factor Proteins 0.000 description 27
HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 26
239000000243 solution Substances 0.000 description 26
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
238000006243 chemical reaction Methods 0.000 description 23
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
239000004480 active ingredient Substances 0.000 description 14
239000012074 organic phase Substances 0.000 description 14
239000002904 solvent Substances 0.000 description 14
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
238000002844 melting Methods 0.000 description 12
230000008018 melting Effects 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
235000011121 sodium hydroxide Nutrition 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 9
-1 alkylene radicals Chemical class 0.000 description 9
238000001816 cooling Methods 0.000 description 9
238000004519 manufacturing process Methods 0.000 description 9
239000003921 oil Substances 0.000 description 9
239000000126 substance Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
239000013543 active substance Substances 0.000 description 8
238000009835 boiling Methods 0.000 description 8
238000010992 reflux Methods 0.000 description 8
238000003756 stirring Methods 0.000 description 8
238000005481 NMR spectroscopy Methods 0.000 description 7
229910052796 boron Inorganic materials 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
238000012360 testing method Methods 0.000 description 7
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
230000036772 blood pressure Effects 0.000 description 6
239000002674 ointment Substances 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
210000004369 blood Anatomy 0.000 description 5
239000008280 blood Substances 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
230000004054 inflammatory process Effects 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
150000003254 radicals Chemical class 0.000 description 5
208000010110 spontaneous platelet aggregation Diseases 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
206010006482 Bronchospasm Diseases 0.000 description 4
241000282414 Homo sapiens Species 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
235000011114 ammonium hydroxide Nutrition 0.000 description 4
230000007885 bronchoconstriction Effects 0.000 description 4
150000001735 carboxylic acids Chemical class 0.000 description 4
210000003169 central nervous system Anatomy 0.000 description 4
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
239000013078 crystal Substances 0.000 description 4
201000010099 disease Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000001990 intravenous administration Methods 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
239000003826 tablet Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
239000003848 thrombocyte activating factor antagonist Substances 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
241000700198 Cavia Species 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
208000006673 asthma Diseases 0.000 description 3
230000037396 body weight Effects 0.000 description 3
206010006451 bronchitis Diseases 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000000470 constituent Substances 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
239000012043 crude product Substances 0.000 description 3
239000000499 gel Substances 0.000 description 3
230000000147 hypnotic effect Effects 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000007858 starting material Substances 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
ZXCIEWBDUAPBJF-MUUNZHRXSA-N 2-O-acetyl-1-O-octadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C ZXCIEWBDUAPBJF-MUUNZHRXSA-N 0.000 description 2
206010002198 Anaphylactic reaction Diseases 0.000 description 2
206010006458 Bronchitis chronic Diseases 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
241000219793 Trifolium Species 0.000 description 2
101150046432 Tril gene Proteins 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
230000002052 anaphylactic effect Effects 0.000 description 2
230000036783 anaphylactic response Effects 0.000 description 2
208000003455 anaphylaxis Diseases 0.000 description 2
210000001772 blood platelet Anatomy 0.000 description 2
150000001733 carboxylic acid esters Chemical class 0.000 description 2
241001233037 catfish Species 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
208000007451 chronic bronchitis Diseases 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
235000008504 concentrate Nutrition 0.000 description 2
239000006071 cream Substances 0.000 description 2
238000009826 distribution Methods 0.000 description 2
239000003480 eluent Substances 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
230000002757 inflammatory effect Effects 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
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231100000566 intoxication Toxicity 0.000 description 2
238000011835 investigation Methods 0.000 description 2
239000007788 liquid Substances 0.000 description 2
OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
150000007530 organic bases Chemical group 0.000 description 2
239000012071 phase Substances 0.000 description 2
230000000770 proinflammatory effect Effects 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
230000009467 reduction Effects 0.000 description 2
230000029058 respiratory gaseous exchange Effects 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000001509 sodium citrate Substances 0.000 description 2
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Inorganic materials [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
239000000829 suppository Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
GYRQGNPJTRTENN-QYLPRCTNSA-N (8r,9s,10r,13s,14s)-10,13-dimethylspiro[2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthrene-17,2'-oxirane]-3-one Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CCC(=O)C=C3CC2)C)CC[C@@]11C)CC11CO1 GYRQGNPJTRTENN-QYLPRCTNSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
MZHUTGQZAZLFKW-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carboxylic acid Chemical compound C1=CC(C(=O)O)=NNC2=CC=CC=C21 MZHUTGQZAZLFKW-UHFFFAOYSA-N 0.000 description 1
JLCYYQOQSAMWTA-UHFFFAOYSA-N 2,3,3,4-tetramethylpentane Chemical compound CC(C)C(C)(C)C(C)C JLCYYQOQSAMWTA-UHFFFAOYSA-N 0.000 description 1
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
UTCWCXZWHKPFDZ-UHFFFAOYSA-N 2-(3-bromopropoxycarbonyl)benzoic acid Chemical compound C1=CC=C(C(=C1)C(=O)O)C(=O)OCCCBr UTCWCXZWHKPFDZ-UHFFFAOYSA-N 0.000 description 1
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Hematology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Preparation Of Clay, And Manufacture Of Mixtures Containing Clay Or Cement (AREA)

DD87305296A 1986-07-25 1987-07-23 Verfahren zur herstellung von neuen 1,4-benzodiozepinen DD266355A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE3625197		1986-07-25

Publications (1)

Publication Number	Publication Date
DD266355A5 true DD266355A5 (de)	1989-03-29

Family

ID=6305976

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD87305296A DD266355A5 (de)	1986-07-25	1987-07-23	Verfahren zur herstellung von neuen 1,4-benzodiozepinen

Country Status (16)

Country	Link
EP (1)	EP0255028A3 (da)
JP (1)	JPS6335574A (da)
KR (1)	KR880001657A (da)
AU (1)	AU603591B2 (da)
DD (1)	DD266355A5 (da)
DK (1)	DK387587A (da)
FI (1)	FI873243A7 (da)
HU (1)	HU197011B (da)
IL (1)	IL83318A0 (da)
NO (1)	NO873108L (da)
NZ (1)	NZ221189A (da)
PL (1)	PL266932A1 (da)
PT (1)	PT85396B (da)
SU (1)	SU1681729A3 (da)
YU (1)	YU136287A (da)
ZA (1)	ZA875446B (da)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8720414D0 (en) *	1987-08-28	1987-10-07	Roussel Lab Ltd	Chemical compounds
US5895785A (en) *	1987-10-20	1999-04-20	Ruth Korth	Treatment and prevention of disorders mediated by LA-paf or endothelial cells
DE4244265C2 (de) *	1992-12-28	1999-08-12	Korth Ruth Maria	Verwendung von Paf-Antagonisten gegen die neue Ausbildung von Paf-Bindungsstellen auf endothelialen Zellen zur Behandlung oder Vorbeugung des Hyperinsulinismus
DE3808283A1 (de) *	1988-03-12	1989-09-21	Boehringer Ingelheim Kg	Neue 3,4,5-substituierte 4h-1,2,4-triazole, ihre herstellung und verwendung
DE3810848A1 (de) *	1988-03-30	1989-10-19	Boehringer Ingelheim Kg	Neue 2,3,4-substituierte imidazole und 3,4,5-substituierte 1,2,4-triazole, ihre herstellung und verwendung
IL91386A0 (en) *	1988-08-24	1990-04-29	Boehringer Ingelheim Kg	Method for treating autoimmune diseases by using a paf antagonist and pharmaceutical compositions comprising it
AU6157190A (en) *	1989-08-19	1991-04-03	Boehringer Ingelheim International Gmbh	Substituted n-heterocycles, their preparation and their use
JP2733708B2 (ja) *	1990-09-22	1998-03-30	カースル産業株式会社	排気口のフィルター装置
JP2520577Y2 (ja) *	1991-05-28	1996-12-18	住友重機械工業株式会社	消石灰溶解注入装置
ATE221779T1 (de) *	1991-11-04	2002-08-15	Ruth-Maria Korth	Behandlung und vorbeugung von erhöhten lyso-paf- spiegel mediierten mentalen erkrankungen mit paf- antagonisten
JPH11188570A (ja)	1997-12-24	1999-07-13	Toyoda Mach Works Ltd	冷風冷却を用いた機械加工装置及び機械加工方法
JP3719324B2 (ja)	1997-12-24	2005-11-24	豊田工機株式会社	冷風冷却を用いた機械加工方法
ES2823180T3 (es) *	2016-07-14	2021-05-06	Bristol Myers Squibb Co	Compuestos bicíclicos sustituidos con heteroarilo

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1332766A (en) *	1971-06-18	1973-10-03	Upjohn Co	Triazolo-benzodiazepines
FR2183716A1 (en) *	1972-05-05	1973-12-21	Centre Etd Ind Pharma	Substd-6-phenyl-4h-imidazo (1,2-a)-1,4-benzo diazepines - - tranquillisers anxiolytics,sedatives and muscle-relaxants
US3880876A (en) *	1972-11-03	1975-04-29	American Home Prod	Process for the preparation of 6-aryl-4H-s-triazolo-{8 4,3-a{9 {8 1,4{9 benzodiazepines
US4663321A (en) *	1984-06-26	1987-05-05	Merck & Co., Inc.	Triazolobenzodiazepines and pharmaceutical use
DE3610848A1 (de) *	1986-04-01	1987-10-15	Boehringer Ingelheim Kg	Neue 1,4-diazepine
US4735941A (en) *	1986-12-23	1988-04-05	Merck & Co., Inc.	1,4-benzodiazepines with 5- and 6-membered heterocyclic rings, useful as gastrointestinal and CNS agents

1987
- 1987-07-20 YU YU01362/87A patent/YU136287A/xx unknown
- 1987-07-20 SU SU874202929A patent/SU1681729A3/ru active
- 1987-07-21 PL PL1987266932A patent/PL266932A1/xx unknown
- 1987-07-22 EP EP87110590A patent/EP0255028A3/de not_active Withdrawn
- 1987-07-23 DD DD87305296A patent/DD266355A5/de not_active IP Right Cessation
- 1987-07-24 HU HU873414A patent/HU197011B/hu not_active IP Right Cessation
- 1987-07-24 ZA ZA875446A patent/ZA875446B/xx unknown
- 1987-07-24 IL IL83318A patent/IL83318A0/xx unknown
- 1987-07-24 AU AU76103/87A patent/AU603591B2/en not_active Ceased
- 1987-07-24 PT PT85396A patent/PT85396B/pt unknown
- 1987-07-24 NO NO873108A patent/NO873108L/no unknown
- 1987-07-24 DK DK387587A patent/DK387587A/da not_active Application Discontinuation
- 1987-07-24 NZ NZ221189A patent/NZ221189A/xx unknown
- 1987-07-24 FI FI873243A patent/FI873243A7/fi not_active Application Discontinuation
- 1987-07-24 JP JP62185347A patent/JPS6335574A/ja active Pending
- 1987-07-25 KR KR1019870008107A patent/KR880001657A/ko not_active Withdrawn

Also Published As

Publication number	Publication date
SU1681729A3 (ru)	1991-09-30
JPS6335574A (ja)	1988-02-16
AU603591B2 (en)	1990-11-22
FI873243A0 (fi)	1987-07-24
DK387587D0 (da)	1987-07-24
HU197011B (en)	1989-02-28
NZ221189A (en)	1990-09-26
PT85396B (de)	1989-10-26
PL266932A1 (en)	1988-09-01
ZA875446B (en)	1989-03-29
AU7610387A (en)	1988-01-28
PT85396A (de)	1987-08-01
FI873243A7 (fi)	1988-01-26
IL83318A0 (en)	1987-12-31
EP0255028A2 (de)	1988-02-03
HUT44788A (en)	1988-04-28
KR880001657A (ko)	1988-04-25
NO873108L (no)	1988-01-26
YU136287A (en)	1990-06-30
EP0255028A3 (de)	1990-03-21
DK387587A (da)	1988-01-26
NO873108D0 (no)	1987-07-24

Legal Events

Date	Code	Title	Description
2001-02-15	ENJ	Ceased due to non-payment of renewal fee

Publication	Publication Date	Title
DE3724164A1 (de)	1988-01-28	Neue 1,4-benzodiazepine, ihre herstellung und verwendung
EP0682027B1 (de)	1997-10-15	Pyrrolopyrimidinderivate mit antiproliferativer Wirkung
AT390257B (de)	1990-04-10	Verfahren zur herstellung neuer imidazo(4,5-b)chinolin-derivate
EP0171728B1 (de)	1989-04-05	Neue Tryptamin-Derivate, ein Verfahren zu ihrer Herstellung und ihre Verwendung
DD146293A5 (de)	1981-02-04	Verfahren zur herstellung von 5-(4-pyridyl)-6-(4-fluorphenyl)-2,3-dihydroimidazo eckige klammer auf 2,1-b eckige klammer zu thiazol,seiner salze und seiner oxide
DE3724031A1 (de)	1988-01-28	Neue hetrazepine und verfahren zu ihrer herstellung
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