BG107259A - Оптически активни 2-аминотетралинови производни, методи за получаването им и терапевтично приложение на фармацевтични състави, които ги съдържат - Google Patents
Оптически активни 2-аминотетралинови производни, методи за получаването им и терапевтично приложение на фармацевтични състави, които ги съдържат Download PDFInfo
- Publication number
- BG107259A BG107259A BG107259A BG10725902A BG107259A BG 107259 A BG107259 A BG 107259A BG 107259 A BG107259 A BG 107259A BG 10725902 A BG10725902 A BG 10725902A BG 107259 A BG107259 A BG 107259A
- Authority
- BG
- Bulgaria
- Prior art keywords
- chf
- nmol
- preparation
- enantiomers
- methylaminotetralin
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title abstract description 25
- 238000000034 method Methods 0.000 title abstract description 12
- 230000008569 process Effects 0.000 title abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 5
- 230000001225 therapeutic effect Effects 0.000 title description 4
- LCGFVWKNXLRFIF-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-2-amine Chemical class C1=CC=C2CC(N)CCC2=C1 LCGFVWKNXLRFIF-UHFFFAOYSA-N 0.000 title 1
- 239000003814 drug Substances 0.000 claims abstract description 12
- 239000000203 mixture Substances 0.000 claims description 19
- MIMDMPWWTWVHFK-UHFFFAOYSA-N 6-(methylamino)-5,6,7,8-tetrahydronaphthalene-1,2-diol;hydrochloride Chemical compound Cl.C1=CC(O)=C(O)C2=C1CC(NC)CC2 MIMDMPWWTWVHFK-UHFFFAOYSA-N 0.000 claims description 14
- 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 12
- 238000001802 infusion Methods 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims description 4
- 238000007069 methylation reaction Methods 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 230000002093 peripheral effect Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 200000000007 Arterial disease Diseases 0.000 claims description 2
- 206010020802 Hypertensive crisis Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 230000036770 blood supply Effects 0.000 claims description 2
- 238000009833 condensation Methods 0.000 claims description 2
- 230000005494 condensation Effects 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 230000001575 pathological effect Effects 0.000 claims description 2
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 claims 1
- 101100137463 Bacillus subtilis (strain 168) ppsA gene Proteins 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 101100342406 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PRS1 gene Proteins 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims 1
- 101150056693 pps1 gene Proteins 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 abstract description 6
- BHDFPNRSDABMPW-UHFFFAOYSA-N 6-(methylamino)-5,6,7,8-tetrahydronaphthalene-1,2-diol Chemical compound C1=CC(O)=C(O)C2=C1CC(NC)CC2 BHDFPNRSDABMPW-UHFFFAOYSA-N 0.000 abstract description 4
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 38
- 102000005962 receptors Human genes 0.000 description 20
- 108020003175 receptors Proteins 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 10
- TWTMQRXNAZGSCE-UHFFFAOYSA-N hydron;[6-(methylamino)-1-(2-methylpropanoyloxy)-5,6,7,8-tetrahydronaphthalen-2-yl] 2-methylpropanoate;chloride Chemical compound Cl.C1=CC(OC(=O)C(C)C)=C(OC(=O)C(C)C)C2=C1CC(NC)CC2 TWTMQRXNAZGSCE-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 230000036772 blood pressure Effects 0.000 description 5
- 230000001077 hypotensive effect Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 206010019280 Heart failures Diseases 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000000747 cardiac effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 229940095064 tartrate Drugs 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 240000007711 Peperomia pellucida Species 0.000 description 3
- 102000004659 Presynaptic Receptors Human genes 0.000 description 3
- 108010003717 Presynaptic Receptors Proteins 0.000 description 3
- TWTMQRXNAZGSCE-PFEQFJNWSA-N [(6r)-6-(methylamino)-1-(2-methylpropanoyloxy)-5,6,7,8-tetrahydronaphthalen-2-yl] 2-methylpropanoate;hydrochloride Chemical compound Cl.C1=CC(OC(=O)C(C)C)=C(OC(=O)C(C)C)C2=C1C[C@H](NC)CC2 TWTMQRXNAZGSCE-PFEQFJNWSA-N 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001640 fractional crystallisation Methods 0.000 description 3
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 3
- LKQPSXAEAAEUCE-UHFFFAOYSA-N methyl n-(5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate Chemical compound C1=CC(OC)=C(OC)C2=C1CC(NC(=O)OC)CC2 LKQPSXAEAAEUCE-UHFFFAOYSA-N 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 230000003285 pharmacodynamic effect Effects 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- FQHKWDHSEAGKNM-UHFFFAOYSA-N 4-(2,3-dimethoxyphenyl)-2-(methoxycarbonylamino)butanoic acid Chemical compound COC(=O)NC(C(O)=O)CCC1=CC=CC(OC)=C1OC FQHKWDHSEAGKNM-UHFFFAOYSA-N 0.000 description 2
- HVKPFRTYUYTGFO-UHFFFAOYSA-N 5,6-dimethoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C(OC)C2=C1CC(NC)CC2 HVKPFRTYUYTGFO-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- OMMYLOLVPCCZQZ-AWEZNQCLSA-N [(6s)-6-(methylamino)-1-(2-methylpropanoyloxy)-5,6,7,8-tetrahydronaphthalen-2-yl] 2-methylpropanoate Chemical compound C1=CC(OC(=O)C(C)C)=C(OC(=O)C(C)C)C2=C1C[C@@H](NC)CC2 OMMYLOLVPCCZQZ-AWEZNQCLSA-N 0.000 description 2
- TWTMQRXNAZGSCE-UQKRIMTDSA-N [(6s)-6-(methylamino)-1-(2-methylpropanoyloxy)-5,6,7,8-tetrahydronaphthalen-2-yl] 2-methylpropanoate;hydrochloride Chemical compound Cl.C1=CC(OC(=O)C(C)C)=C(OC(=O)C(C)C)C2=C1C[C@@H](NC)CC2 TWTMQRXNAZGSCE-UQKRIMTDSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000003943 catecholamines Chemical class 0.000 description 2
- 210000003710 cerebral cortex Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 208000021822 hypotensive Diseases 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- XVVNIBWOAAEHBD-UHFFFAOYSA-N methyl n-(5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-n-methylcarbamate Chemical compound C1=CC(OC)=C(OC)C2=C1CC(N(C)C(=O)OC)CC2 XVVNIBWOAAEHBD-UHFFFAOYSA-N 0.000 description 2
- NWABBOAPGNNYAP-UHFFFAOYSA-N methyl n-(5,6-dimethoxy-1-oxo-3,4-dihydro-2h-naphthalen-2-yl)carbamate Chemical compound COC1=CC=C2C(=O)C(NC(=O)OC)CCC2=C1OC NWABBOAPGNNYAP-UHFFFAOYSA-N 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- JQEUPNKUYMHYPW-UHFFFAOYSA-N n-methyl-1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C1=CC=C2C(NC)CCCC2=C1 JQEUPNKUYMHYPW-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 125000006823 (C1-C6) acyl group Chemical group 0.000 description 1
- JRZGPXSSNPTNMA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-1-amine Chemical class C1=CC=C2C(N)CCCC2=C1 JRZGPXSSNPTNMA-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 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
- ZROCNTZTEKIWKT-UHFFFAOYSA-N 4-(2,3-dimethoxyphenyl)-2-oxobut-3-enoic acid Chemical compound COC1=CC=CC(C=CC(=O)C(O)=O)=C1OC ZROCNTZTEKIWKT-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
- 108090000371 Esterases Proteins 0.000 description 1
- 241000270290 Gekkota Species 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 102000004879 Racemases and epimerases Human genes 0.000 description 1
- 108090001066 Racemases and epimerases Proteins 0.000 description 1
- GOTMKOSCLKVOGG-UHFFFAOYSA-N SCH 23390 Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1C1=CC=CC=C1 GOTMKOSCLKVOGG-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002807 Thiomer Polymers 0.000 description 1
- OMMYLOLVPCCZQZ-CQSZACIVSA-N [(6r)-6-(methylamino)-1-(2-methylpropanoyloxy)-5,6,7,8-tetrahydronaphthalen-2-yl] 2-methylpropanoate Chemical compound C1=CC(OC(=O)C(C)C)=C(OC(=O)C(C)C)C2=C1C[C@H](NC)CC2 OMMYLOLVPCCZQZ-CQSZACIVSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 230000002562 anti-bronchospastic effect Effects 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- VIHAEDVKXSOUAT-UHFFFAOYSA-N but-2-en-4-olide Chemical compound O=C1OCC=C1 VIHAEDVKXSOUAT-UHFFFAOYSA-N 0.000 description 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
- 229960004484 carbachol Drugs 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000005202 decontamination Methods 0.000 description 1
- 230000003588 decontaminative effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 108010010865 dopamine-I receptor Proteins 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- -1 isobutyroyl ester Chemical class 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000006626 methoxycarbonylamino group Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- CRWACYYGENOWCW-UHFFFAOYSA-N methyl n-[2-(2,3-dimethoxyphenyl)-5-oxo-2h-furan-4-yl]carbamate Chemical compound O1C(=O)C(NC(=O)OC)=CC1C1=CC=CC(OC)=C1OC CRWACYYGENOWCW-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910000096 monohydride Inorganic materials 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000002182 neurohumoral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000011916 stereoselective reduction Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 230000001161 sympathoadrenergic effect Effects 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000005062 tracheal ring Anatomy 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C219/26—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/64—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2000MI001053A IT1318516B1 (it) | 2000-05-12 | 2000-05-12 | Derivati 2-amminotetralinici otticamente attivi, procedimenti per laloro preparazione e impiego terapeutico delle corrispondenti |
| PCT/EP2001/005212 WO2001085668A1 (en) | 2000-05-12 | 2001-05-08 | Optically active 2-aminotetralin derivatives, the processes for the preparation thereof and the therapeutical use of pharmaceutical compositions containing them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BG107259A true BG107259A (bg) | 2003-07-31 |
Family
ID=11445033
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG107259A BG107259A (bg) | 2000-05-12 | 2002-11-08 | Оптически активни 2-аминотетралинови производни, методи за получаването им и терапевтично приложение на фармацевтични състави, които ги съдържат |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20040102652A1 (it) |
| EP (1) | EP1280759A1 (it) |
| JP (1) | JP2003532700A (it) |
| KR (1) | KR20020094014A (it) |
| AR (1) | AR028097A1 (it) |
| AU (1) | AU2001274000A1 (it) |
| BG (1) | BG107259A (it) |
| BR (1) | BR0110989A (it) |
| CZ (1) | CZ20023718A3 (it) |
| HU (1) | HUP0302027A2 (it) |
| IL (1) | IL152751A0 (it) |
| IT (1) | IT1318516B1 (it) |
| NO (1) | NO20025393L (it) |
| PL (1) | PL357466A1 (it) |
| SK (1) | SK16052002A3 (it) |
| TN (1) | TNSN01072A1 (it) |
| WO (1) | WO2001085668A1 (it) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10066158B4 (de) * | 2000-08-24 | 2007-08-09 | Neurobiotec Gmbh | Verwendung eines transdermalen therapeutischen Systems zur Behandlung des Restless-Legs-Syndroms |
| DE10053397A1 (de) * | 2000-10-20 | 2002-05-02 | Schering Ag | Verwendung eines dopaminergen Wirkstoffes zur Behandlung von dopaminerg behandelbaren Erkrankungen |
| DE10064453A1 (de) * | 2000-12-16 | 2002-07-04 | Schering Ag | Verwendung eines dopaminergen Wirkstoffes zur Behandlung von dopaminerg behandelbaren Erkrankungen |
| EP1384708A1 (en) * | 2002-07-26 | 2004-01-28 | CHIESI FARMACEUTICI S.p.A. | Process for the manufacture of form I of nolomirole hydrochloride |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5214156A (en) * | 1988-03-25 | 1993-05-25 | The Upjohn Company | Therapeutically useful tetralin derivatives |
| IT1269584B (it) * | 1994-04-26 | 1997-04-08 | Chiesi Farma Spa | Procedimento per la preparazione di derivati di 5,6-diidrossi- 2-ammino-1,2,3,4- tetraidronaftalene |
| IT1275935B1 (it) * | 1995-03-17 | 1997-10-24 | Chiesi Farma Spa | Derivato di aminotetralina per la terapia di malattie cardiovascolari |
| IT1313583B1 (it) * | 1999-07-30 | 2002-09-09 | Chiesi Farma Spa | Derivati 2-amminotetralinici per la terapia del glaucoma. |
-
2000
- 2000-05-08 IL IL15275100A patent/IL152751A0/xx unknown
- 2000-05-12 IT IT2000MI001053A patent/IT1318516B1/it active
-
2001
- 2001-05-08 HU HU0302027A patent/HUP0302027A2/hu unknown
- 2001-05-08 SK SK1605-2002A patent/SK16052002A3/sk not_active Application Discontinuation
- 2001-05-08 JP JP2001582269A patent/JP2003532700A/ja active Pending
- 2001-05-08 CZ CZ20023718A patent/CZ20023718A3/cs unknown
- 2001-05-08 US US10/275,894 patent/US20040102652A1/en not_active Abandoned
- 2001-05-08 BR BR0110989-8A patent/BR0110989A/pt not_active Withdrawn
- 2001-05-08 EP EP01940415A patent/EP1280759A1/en not_active Withdrawn
- 2001-05-08 WO PCT/EP2001/005212 patent/WO2001085668A1/en not_active Application Discontinuation
- 2001-05-08 AU AU2001274000A patent/AU2001274000A1/en not_active Abandoned
- 2001-05-08 PL PL01357466A patent/PL357466A1/xx not_active Application Discontinuation
- 2001-05-08 KR KR1020027014884A patent/KR20020094014A/ko not_active Application Discontinuation
- 2001-05-11 TN TNTNSN01072A patent/TNSN01072A1/fr unknown
- 2001-05-11 AR ARP010102255A patent/AR028097A1/es not_active Application Discontinuation
-
2002
- 2002-11-08 BG BG107259A patent/BG107259A/bg unknown
- 2002-11-11 NO NO20025393A patent/NO20025393L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| BR0110989A (pt) | 2003-12-30 |
| ITMI20001053A1 (it) | 2001-11-12 |
| IT1318516B1 (it) | 2003-08-27 |
| TNSN01072A1 (fr) | 2005-11-10 |
| HUP0302027A2 (hu) | 2003-10-28 |
| ITMI20001053A0 (it) | 2000-05-12 |
| CZ20023718A3 (cs) | 2003-02-12 |
| SK16052002A3 (sk) | 2003-03-04 |
| KR20020094014A (ko) | 2002-12-16 |
| US20040102652A1 (en) | 2004-05-27 |
| JP2003532700A (ja) | 2003-11-05 |
| AU2001274000A1 (en) | 2001-11-20 |
| EP1280759A1 (en) | 2003-02-05 |
| IL152751A0 (en) | 2003-06-24 |
| WO2001085668A1 (en) | 2001-11-15 |
| NO20025393L (no) | 2003-01-13 |
| WO2001085668A8 (en) | 2002-02-21 |
| AR028097A1 (es) | 2003-04-23 |
| PL357466A1 (en) | 2004-07-26 |
| NO20025393D0 (no) | 2002-11-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2587368T3 (es) | Derivados deuterados de catecolamina y medicamentos que comprenden dichos compuestos | |
| JPS6315256B2 (it) | ||
| CN106800537B (zh) | 丁苯酞-替米沙坦杂合物及其制备方法和用途 | |
| BG60411B2 (bg) | Бис-диметоксиметил(триметоксибензил)изохинолинови соли, получаване и фармацевтични състави,които ги съдържат | |
| JP2009007258A (ja) | Ｐａｉ−１産生抑制作用を有する３−アニリノ−２−シクロアルケノン誘導体 | |
| WO2004014290A2 (en) | R-bambuterol, its preparation and therapeutic uses | |
| BG107259A (bg) | Оптически активни 2-аминотетралинови производни, методи за получаването им и терапевтично приложение на фармацевтични състави, които ги съдържат | |
| JPS60252474A (ja) | （−）―３―（４―フェニル―１―ピペラジニル）―１，２―プロパンジオールを有効成分とする鎮咳剤 | |
| JP5903166B2 (ja) | ブチルフタリドの誘導体、並びにその製造法及び使用 | |
| JP2001514632A (ja) | 新規ヘテロサイクリック化合物 | |
| JPS61165324A (ja) | 心臓脈管系疾患治療剤 | |
| PT87360B (pt) | Satelite duplo com denteado reforcado para articulacao micrometrica utilizada mais especialmente nos bancos de veiculos | |
| CN116178368A (zh) | 一种甲状腺激素受体激动剂及其制备方法和应用 | |
| US4562206A (en) | Orally effective inotropic compounds | |
| EP0146159B1 (en) | Ether of n-propanolamine derivative | |
| JP2002508776A (ja) | （Ｓ）３，４，５−トリメトキシ安息香酸２−メチルアミノ−２−フェニル−ｎ−ブチルおよび慢性疼痛の治療におけるその使用 | |
| EP0112252B1 (fr) | Enantiomères lévogyres des dérivés de la tétrahydro-5,6,13,13a 8H-dibenzo(a, g)quinolizine, procédés d'obtention, compositions pharmaceutiques les contenant et application | |
| KR0148755B1 (ko) | 신규 테트라하이드로이소퀴놀린계 화합물 및 그의 염 | |
| IE902313L (en) | 2-amino-1,2,3,4-tetrahydronaphthalenes | |
| JP3247763B2 (ja) | キサンチン誘導体からなる血液循環の中断による神経損傷の治療用医薬 | |
| NZ199008A (en) | 2,3,3a,4,5,6-hexahydro-ih-indolo(3,2,1-de)(1,5)-naphthyridines | |
| JPS59161380A (ja) | ±２−〔（３，４−メチレンジオキシ）フエネチル〕−５−〔（３−カルボキシアミド−４−ヒドロキシ）−α−ヒドロキシベンジル〕ピロリジン類 | |
| KR790001860B1 (ko) | 프로스타논산의 제조방법 | |
| JPH0376302B2 (it) | ||
| JPH0710851A (ja) | アミノアルコール誘導体及びその用途 |