HU198494B - Process for producing new 3,4-dihydro-5h-2,3-benzodiazepine derivative and acid addition salts thereof, as well as pharmaceutical compositions comprising same - Google Patents
Process for producing new 3,4-dihydro-5h-2,3-benzodiazepine derivative and acid addition salts thereof, as well as pharmaceutical compositions comprising same Download PDFInfo
- Publication number
- HU198494B HU198494B HU863594A HU359486A HU198494B HU 198494 B HU198494 B HU 198494B HU 863594 A HU863594 A HU 863594A HU 359486 A HU359486 A HU 359486A HU 198494 B HU198494 B HU 198494B
- Authority
- HU
- Hungary
- Prior art keywords
- hydride
- compound
- acid addition
- formula
- dihydro
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims abstract description 14
- 150000003839 salts Chemical class 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title claims description 12
- 230000008569 process Effects 0.000 title claims description 12
- ZOIDJSXQPWPCDP-UHFFFAOYSA-N 4,5-dihydro-3h-2,3-benzodiazepine Chemical class C1=NNCCC2=CC=CC=C21 ZOIDJSXQPWPCDP-UHFFFAOYSA-N 0.000 title claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- 230000009467 reduction Effects 0.000 claims abstract description 8
- 150000004678 hydrides Chemical class 0.000 claims abstract description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- -1 lithium aluminum hydride Chemical group 0.000 claims description 9
- 239000012279 sodium borohydride Substances 0.000 claims description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 229910052987 metal hydride Inorganic materials 0.000 claims description 6
- 150000004681 metal hydrides Chemical class 0.000 claims description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 5
- 239000008298 dragée Substances 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 claims description 3
- YVOHCRLDUPTKOH-UHFFFAOYSA-N 5h-2,3-benzodiazepine Chemical compound C1C=NN=CC2=CC=CC=C12 YVOHCRLDUPTKOH-UHFFFAOYSA-N 0.000 claims description 3
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 3
- UCXUKTLCVSGCNR-UHFFFAOYSA-N diethylsilane Chemical compound CC[SiH2]CC UCXUKTLCVSGCNR-UHFFFAOYSA-N 0.000 claims description 3
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 3
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 claims description 3
- 229910000103 lithium hydride Inorganic materials 0.000 claims description 3
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 3
- 239000011877 solvent mixture Substances 0.000 claims description 3
- 230000004936 stimulating effect Effects 0.000 claims 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 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- 150000004645 aluminates Chemical class 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910000077 silane Inorganic materials 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000000839 emulsion Substances 0.000 claims 1
- 239000000945 filler Substances 0.000 claims 1
- 239000000796 flavoring agent Substances 0.000 claims 1
- 235000013355 food flavoring agent Nutrition 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- ANAFTYVSHCSQPP-UHFFFAOYSA-N lithium;trimethoxyalumane Chemical compound [Li].CO[Al](OC)OC ANAFTYVSHCSQPP-UHFFFAOYSA-N 0.000 claims 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 239000000829 suppository Substances 0.000 claims 1
- 239000004094 surface-active agent Substances 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- AQTITSBNGSVQNZ-UHFFFAOYSA-N GYKI 52895 Chemical compound N=1NC(C)CC2=CC=3OCOC=3C=C2C=1C1=CC=C(N)C=C1 AQTITSBNGSVQNZ-UHFFFAOYSA-N 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 6
- LFBZZHVSGAHQPP-UHFFFAOYSA-N GYKI 52466 Chemical compound C12=CC=3OCOC=3C=C2CC(C)=NN=C1C1=CC=C(N)C=C1 LFBZZHVSGAHQPP-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003291 dopaminomimetic effect Effects 0.000 abstract description 2
- 230000003287 optical effect Effects 0.000 abstract 2
- 208000027089 Parkinsonian disease Diseases 0.000 abstract 1
- 206010034010 Parkinsonism Diseases 0.000 abstract 1
- 230000004064 dysfunction Effects 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- 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
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 229960003878 haloperidol Drugs 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 230000004899 motility Effects 0.000 description 5
- 230000037023 motor activity Effects 0.000 description 5
- 230000002269 spontaneous effect Effects 0.000 description 5
- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- MKWRMWFMOVRTRH-UHFFFAOYSA-N 4,5-dihydro-3h-1,2-benzodiazepine Chemical class C1CCN=NC2=CC=CC=C21 MKWRMWFMOVRTRH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 206010044565 Tremor Diseases 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229940049706 benzodiazepine Drugs 0.000 description 3
- 125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920002261 Corn starch Polymers 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
- 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 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010039424 Salivary hypersecretion Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 239000002269 analeptic agent Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229960002802 bromocriptine Drugs 0.000 description 2
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 2
- 239000003874 central nervous system depressant Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940052760 dopamine agonists Drugs 0.000 description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 208000026451 salivation Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- JSUAJTLKVREZHV-UHFFFAOYSA-N 1-[4-(1-pyrrolidinyl)but-2-ynyl]pyrrolidine Chemical compound C1CCCN1CC#CCN1CCCC1 JSUAJTLKVREZHV-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- STVGZMDXLCKKHX-UHFFFAOYSA-N 5h-1,2-benzodiazepine Chemical class C1C=CN=NC2=CC=CC=C12 STVGZMDXLCKKHX-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 229910020889 NaBH3 Inorganic materials 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000002895 emetic Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- HWYHDWGGACRVEH-UHFFFAOYSA-N n-methyl-n-(4-pyrrolidin-1-ylbut-2-ynyl)acetamide Chemical compound CC(=O)N(C)CC#CCN1CCCC1 HWYHDWGGACRVEH-UHFFFAOYSA-N 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000003368 psychostimulant agent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Priority Applications (23)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU863594A HU198494B (en) | 1986-08-15 | 1986-08-15 | Process for producing new 3,4-dihydro-5h-2,3-benzodiazepine derivative and acid addition salts thereof, as well as pharmaceutical compositions comprising same |
| AT0202187A ATA202187A (de) | 1986-08-15 | 1987-08-11 | Verfahren zur herstellung von 1-(4-aminophenyl)4-methyl-7,8-methylendioxy-3,4-dihydro-5h-2,3benzodiazepin und seine saeureadditionssalze |
| CH3115/87A CH673652A5 (en, 2012) | 1986-08-15 | 1987-08-12 | |
| YU151487A YU46223B (sh) | 1986-08-15 | 1987-08-13 | Postupak za dobivanje 1-/4-aminofenil/-4-metil-7,8-metilendioksi-3,4-dihid ro-5h-2,3-benzodiazepina |
| FI873525A FI85706C (fi) | 1986-08-15 | 1987-08-14 | Foerfarande foer framstaellning av nytt terapeutiskt anvaendbart 1-(4-aminofenyl)-4-metyl -7,8-metylendioxi-3,4-dihydro-5h-2,3-bensodiazepin och syraadditionssalter daerav. |
| ES8702415A ES2004985A6 (es) | 1986-08-15 | 1987-08-14 | Procedimiento de preparacion de 1-4aminofenil-4-metil-7,8-metilendioxi-3,4-dihidro-5h-2,3-benzodiazepina y sus sales de adicion acidas |
| CA000544626A CA1284322C (en) | 1986-08-15 | 1987-08-14 | 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-3,4- dihydro-5h-2,3-benzodiazepine and a process for preparing same |
| NL8701909A NL8701909A (nl) | 1986-08-15 | 1987-08-14 | 1-(4-aminofenyl)-4-methyl-7,8-methyleendioxy-3,4-dihydro-5h-2,3-benzodiazepine, zuur-additiezouten daarvan en werkwijze voor de bereiding ervan. |
| SE8703169A SE467357B (sv) | 1986-08-15 | 1987-08-14 | 1-(4-aminofenyl)-4-metyl-7,8-metylendioxi-3,4-dihydro-5h-2,3-bensodiazepin, syraadditionssalter daerav samt foerfarande foer framstaellning av desamma |
| JP62201967A JPS6399073A (ja) | 1986-08-15 | 1987-08-14 | １−（４−アミノフェニル）−４−メチル−７，８−メチレンジオキシ−３，４−ジヒドロ−５ｈ−２，３−ベンゾジアゼピン、その光学活性体およびラセミ体、および前記化合物の酸付加塩、その製造方法、並びに前記化合物を含む薬剤、その製造方法、およびそれによる治療方法 |
| DD87306060A DD265627A5 (de) | 1986-08-15 | 1987-08-14 | Verfahren zur herstellung von 1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-3,4-dihydro-5h-2,3-benzodiazepin |
| NO873426A NO164656C (no) | 1986-08-15 | 1987-08-14 | Analogifremgangsmaate for fremstilling av terapeutisk aktivt 1-(4-amionfenyl)-4-methyl-7,8-methylendioxy-3,4-dihydro-5h-2,3-benzodiazepin. |
| CS876007A CS264150B2 (en) | 1986-08-15 | 1987-08-14 | Process for preparing new 1-/4-aminophenyl/-4-methyl-7,8-methylendioxy-3,4-dihydro-5h-2,3-benzodiazepine |
| BE8700909A BE1002415A4 (fr) | 1986-08-15 | 1987-08-14 | 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-3,4-dihydro-5h-2,3-benzodiazepine, ses sels d'addition acides et procede pour les preparer. |
| SU874203196A RU1779251C (ru) | 1986-08-15 | 1987-08-14 | Способ получени 1-(4-аминофенил)-4-метил-7,8-метилендиокси-3,4-дигидро-5Н-2,3-бензодиазепина или его кислотно-аддитивных солей |
| IT21667/87A IT1222508B (it) | 1986-08-15 | 1987-08-14 | 1-(4-aminofil) 4-metil 7,8-metilendiossi-3,4-diidro-5h-2,3-benzodiazepina,suoi sali di addizione acida e procedimento per la loro preparazione |
| DE19873727226 DE3727226A1 (de) | 1986-08-15 | 1987-08-14 | 1-(4'-(amino)-phenyl-4-(methyl)-7,8-(methylendioxy)-3,4-di-(hydro)-5h-2,3-benzodiazepin und seine saeureadditionssalze, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| AU76880/87A AU596206B2 (en) | 1986-08-15 | 1987-08-14 | 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-3,4-hydro-5h- 2,3- benzodiazepine acid addition salts thereof and process for preparing same |
| PL1987267326A PL148535B1 (en) | 1986-08-15 | 1987-08-14 | Method of obtaining novel 1-/4-aminophenyl/-4-methyl-7,8-methylenedioxy- 3,4-dihydro-5h-2,3-benzosiazepin and its addition salt with acids |
| FR878711578A FR2602773B1 (fr) | 1986-08-15 | 1987-08-14 | 0- (4-aminophenyl)- 4 -methyl - 7,8 - methylenedioxy- 3,4 -dihydro - 5h - 2,3 - benzodiazepine, ses sels d'addition acides, procede pour les preparer et medicaments les contenant |
| GB8719265A GB2194236B (en) | 1986-08-15 | 1987-08-14 | 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-3,4-dihydro-5h-2,3-benzodiazepine, acid addition salts thereof and process for preparing same |
| DK424887A DK164555C (da) | 1986-08-15 | 1987-08-14 | 1-(4-aminofenyl)-4-metyl-7,8-metylendioxy-3,4-dihydro-5h-2,3-benzodiazepin, syreadditionssalte deraf, fremgangsmaade til fremstilling heraf samt farmaceutiske praeparater med cns-stimulerende virkning indeholdende saadanne forbindelser |
| US07/087,341 US4835152A (en) | 1986-08-15 | 1987-08-20 | 1-(4-Aminophenyl)-4-methyl-7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine and acid addition salts thereof same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU863594A HU198494B (en) | 1986-08-15 | 1986-08-15 | Process for producing new 3,4-dihydro-5h-2,3-benzodiazepine derivative and acid addition salts thereof, as well as pharmaceutical compositions comprising same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT47287A HUT47287A (en) | 1989-02-28 |
| HU198494B true HU198494B (en) | 1989-10-30 |
Family
ID=10964707
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU863594A HU198494B (en) | 1986-08-15 | 1986-08-15 | Process for producing new 3,4-dihydro-5h-2,3-benzodiazepine derivative and acid addition salts thereof, as well as pharmaceutical compositions comprising same |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US4835152A (en, 2012) |
| JP (1) | JPS6399073A (en, 2012) |
| AT (1) | ATA202187A (en, 2012) |
| AU (1) | AU596206B2 (en, 2012) |
| BE (1) | BE1002415A4 (en, 2012) |
| CA (1) | CA1284322C (en, 2012) |
| CH (1) | CH673652A5 (en, 2012) |
| CS (1) | CS264150B2 (en, 2012) |
| DD (1) | DD265627A5 (en, 2012) |
| DE (1) | DE3727226A1 (en, 2012) |
| DK (1) | DK164555C (en, 2012) |
| ES (1) | ES2004985A6 (en, 2012) |
| FI (1) | FI85706C (en, 2012) |
| FR (1) | FR2602773B1 (en, 2012) |
| GB (1) | GB2194236B (en, 2012) |
| HU (1) | HU198494B (en, 2012) |
| IT (1) | IT1222508B (en, 2012) |
| NL (1) | NL8701909A (en, 2012) |
| NO (1) | NO164656C (en, 2012) |
| PL (1) | PL148535B1 (en, 2012) |
| RU (1) | RU1779251C (en, 2012) |
| SE (1) | SE467357B (en, 2012) |
| YU (1) | YU46223B (en, 2012) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU219778B (hu) * | 1990-12-21 | 2001-07-30 | Gyógyszerkutató Intézet Közös Vállalat | Eljárás N-acil-2,3-benzodiazepin-származékok, savaddíciós sóik és az ezeket tartalmazó gyógyászati készítmények előállítására, valamint a vegyületek egy csoportja, és az ezeket tartalmazó gyógyászati készítmények |
| HU206719B (en) * | 1990-12-21 | 1992-12-28 | Gyogyszerkutato Intezet | Process for producing 1-/4-acylamino-phenyl/-7,8-methylenedioxy-5h-2,3-benzodiazepine derivatives, acid addicional salts and pharmaceutical compositions containing them |
| US5639751A (en) * | 1990-12-21 | 1997-06-17 | Cyogyszerkutato Intezet Kft | N-acyl-2,3-benzodiazepine derivatives for treating acute and chronic neurodegenerative disorders |
| US6288057B1 (en) * | 1994-08-31 | 2001-09-11 | Eli Lilly And Company | Physical form of dihydro-2,3-benzodiazepine derivative |
| TR199501071A2 (tr) * | 1994-08-31 | 1996-06-21 | Lilly Co Eli | Dihidro-2,3-benzodiazepin türevlerinin üretilmesi icin stereoselektif islem. |
| PL181112B1 (pl) * | 1995-03-28 | 2001-05-31 | Eli Lilly & Co | Nowa fizyczna postać (R)-7-acetylo-5-(4-aminofenylo)-8,9-dihydro-8-metylo-7H-1,3-dioksolo[4,5-h] [2,3]-benzodiazepiny, sposób jej otrzymywania oraz kompozycja farmaceutyczna |
| US5891871A (en) * | 1996-03-21 | 1999-04-06 | Cocensys, Inc. | Substituted 2,3-benzodiazepin-4-ones and the use thereof |
| UA67749C2 (uk) * | 1997-08-12 | 2004-07-15 | Егіш Дьйодьсердьяр Рт. | Похідна 8-заміщеного-9н-1,3-діоксол/4,5-h//2,3/бензодіазепіну з властивостями амра/каїнатного антагоніста, спосіб одержання похідних, фармацевтична композиція (варіанти), спосіб її одержання та спосіб лікування |
| US6649607B2 (en) * | 2001-05-18 | 2003-11-18 | Vela Pharmaceuticals, Inc. | Compositions and methods for treating or preventing convulsions or seizures |
| EP1575521A4 (en) * | 2002-12-03 | 2008-04-30 | Vela Acquisition Corp | PHARMACEUTICAL COMPOSITION OF 1- (3-HYDROXY-4-METHOXYPHENYL) -4-METHYL-5-ETHYL-7,8-DIMETHOXY-5H-2,3-BENZODIAZEPINE AND ITS USE |
| US7022700B2 (en) * | 2002-12-03 | 2006-04-04 | Vela Pharmaceuticals, Inc. | Method of increasing neutrophil production using optically-pure (R)-2,3-benzodiazepines |
| CA2508542A1 (en) * | 2002-12-03 | 2004-06-17 | Vela Pharmaceuticals, Inc. | Pharmaceutical composition of 1-(3,4-dimethoxyphenyl)-4-methyl-5-ethyl-7-methoxy-8-hydroxy-5h-2,3-benzodiazepine and uses thereof |
| US6864251B2 (en) * | 2002-12-03 | 2005-03-08 | Vela Pharmaceuticals, Inc. | Treatment of LTB4-mediated inflammatory disorders with optically-pure (R)-2,3-benzodiazepines |
| US6638928B1 (en) | 2002-12-03 | 2003-10-28 | Vela Pharmaceuticals, Inc. | Treatment of irritable bowel syndrome and nonulcer dyspepsia with substituted 2,3-benzodiazepines |
| US20040162284A1 (en) * | 2003-02-19 | 2004-08-19 | Harris Herbert W. | Method of lowering body temperature with (S) tofisopam |
| US20040224943A1 (en) * | 2003-02-19 | 2004-11-11 | Leventer Steven M. | Method of lowering body temperature with (R) - 2,3-benzodiazepines |
| CA2525273C (en) * | 2003-05-16 | 2012-04-17 | Vela Pharmaceuticals, Inc. | Treatment of gastrointestinal dysfunction and related stress with an enantiomerically-pure (r) 2,3-benzodiazepine |
| US20070021412A1 (en) * | 2003-05-16 | 2007-01-25 | Vela Pharmaceuticals, Inc. | Treatment of gastrointestinal dysfunction and related stress with an enantiomerically-pure (S) 2,3-benzodiazepine |
| US20040254173A1 (en) * | 2003-06-13 | 2004-12-16 | Leventer Steven M. | Modulation of dopamine responses with substituted (S)-2,3-benzodiazepines |
| US20050096464A1 (en) * | 2003-10-30 | 2005-05-05 | Heikki Heikkila | Separation process |
| EP4197536A1 (en) * | 2021-12-20 | 2023-06-21 | Universitat de València | Haloperidol for use in the treatment of spinal muscular atrophy |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU186760B (en) * | 1981-03-12 | 1985-09-30 | Gyogyszerkutato Intezet | Process for preparing 3,4-dihydro-5h-2,3-aenzodiazepine derivatives |
| DE3319491A1 (de) * | 1982-06-19 | 1983-10-13 | Alps Electric Co., Ltd., Tokyo | Papierfuehrungsmechanismus fuer schreibgeraete |
| HU191698B (en) * | 1984-07-27 | 1987-03-30 | Gyogyszerkutato Intezet | Process for producing new 1-aryl-5h-2beta-benzodiazepines |
-
1986
- 1986-08-15 HU HU863594A patent/HU198494B/hu not_active IP Right Cessation
-
1987
- 1987-08-11 AT AT0202187A patent/ATA202187A/de not_active Application Discontinuation
- 1987-08-12 CH CH3115/87A patent/CH673652A5/de not_active IP Right Cessation
- 1987-08-13 YU YU151487A patent/YU46223B/sh unknown
- 1987-08-14 DK DK424887A patent/DK164555C/da not_active IP Right Cessation
- 1987-08-14 GB GB8719265A patent/GB2194236B/en not_active Expired - Lifetime
- 1987-08-14 JP JP62201967A patent/JPS6399073A/ja active Pending
- 1987-08-14 BE BE8700909A patent/BE1002415A4/fr not_active IP Right Cessation
- 1987-08-14 NO NO873426A patent/NO164656C/no unknown
- 1987-08-14 ES ES8702415A patent/ES2004985A6/es not_active Expired
- 1987-08-14 FR FR878711578A patent/FR2602773B1/fr not_active Expired - Lifetime
- 1987-08-14 CA CA000544626A patent/CA1284322C/en not_active Expired - Lifetime
- 1987-08-14 RU SU874203196A patent/RU1779251C/ru active
- 1987-08-14 DD DD87306060A patent/DD265627A5/de not_active IP Right Cessation
- 1987-08-14 AU AU76880/87A patent/AU596206B2/en not_active Ceased
- 1987-08-14 SE SE8703169A patent/SE467357B/sv not_active IP Right Cessation
- 1987-08-14 IT IT21667/87A patent/IT1222508B/it active
- 1987-08-14 PL PL1987267326A patent/PL148535B1/pl unknown
- 1987-08-14 DE DE19873727226 patent/DE3727226A1/de not_active Withdrawn
- 1987-08-14 CS CS876007A patent/CS264150B2/cs unknown
- 1987-08-14 FI FI873525A patent/FI85706C/fi not_active IP Right Cessation
- 1987-08-14 NL NL8701909A patent/NL8701909A/nl not_active Application Discontinuation
- 1987-08-20 US US07/087,341 patent/US4835152A/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HU198494B (en) | Process for producing new 3,4-dihydro-5h-2,3-benzodiazepine derivative and acid addition salts thereof, as well as pharmaceutical compositions comprising same | |
| US4423044A (en) | 3,4-Dihydro-5H-2,3-benzodiazepine derivatives and pharmaceutical use thereof | |
| US3637740A (en) | Aminobenzocycloalkane compounds | |
| CA2110574A1 (en) | Tryptamine analogues, their synthesis and their use as 5-ht1-like or 5-ht2 receptor agonists | |
| US3704299A (en) | 5-oxomorpholinyl-2,1-benzisothiazolines | |
| IE58155B1 (en) | Pyrrolidinone derivatives, processes for their preparation and pharmaceutical compositions containing them | |
| GB1569249A (en) | 2-(2,2-diarylalkyl)1-azabicyclo(2.2.2)octane and compounds | |
| US3592824A (en) | 3-substituted amino-1,2,3,4-tetrahydrocarbazoles | |
| US4528289A (en) | Corynantheine derivates, processes for their preparation, and their use | |
| US3253034A (en) | Amino-phenylethanols | |
| EP0368188B1 (en) | 1,2,3,4-Tetrahydro-1,9-acridinediamines, a process for their preparation and their use as medicaments | |
| US3758691A (en) | Illness new substituted hydroxyphenyl-alkylamines in the treatment of mental | |
| GB2297749A (en) | 1-[2-(substituted vinyl)]-3,4-dihydro-5H-2,3-benzodiazepine derivatives | |
| US3458635A (en) | Compositions containing 3-di-substituted methylene pyrrolidines and methods of treating depression | |
| US4977176A (en) | Pilocarpine compounds which are used as pharmaceutical agents | |
| US3499003A (en) | 3-(2-(3-aminopyrrolidinyl)-ethyl)-indoles | |
| US3985732A (en) | 1,2,3,11A-Tetrahydro-10-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5,11(10H)-diones | |
| US3732248A (en) | 3-substituted-1-phenyl indolinones | |
| US3681501A (en) | Pharmaceutical compositions and methods for producing a depressant effect on the central nervous system with piperidyl butanones | |
| KR830001667B1 (ko) | 페닐 퀴놀리지딘의 제조방법 | |
| US3274248A (en) | N-1, 1-bis-[aminophenyl]-propyl-amines and salts thereof | |
| US5225416A (en) | 1,2,3,6-tetrahydropyridine derivatives useful for improving cerebral blood circulation | |
| US3564012A (en) | 5,7-dimethoxy-tryptamines | |
| US3766170A (en) | 3-benzazepines and salts thereof | |
| US3542927A (en) | Reduction of blood sugar levels with aminomethylindoles |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HPC4 | Succession in title of patentee |
Owner name: BIOGAL GYOGYSZERGYAR RT,HU |
|
| HMM4 | Cancellation of final prot. due to non-payment of fee | ||
| HRH9 | Withdrawal of annulment decision | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |