CS220271B1 - Substituted aryloxypropanolamines, salts and their production - Google Patents
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Abstract
Vynález sa týká substituovaných aryloxypropanolamínov obecného vzorca I OH OCH^HCH^NHR2 \Q^-NHCOOR (l‘)> kde R1 je alkyl aleho/a alkloxylalkyl s. 2 až 5 atómami uhlíka, piriamy alebo rozvětvený alkenyl si 2i až 5 atémami uhlíka aleho/a eyteloalkyl· s 3 až 6 atómami· uhlíka a® je rozvětvený alkyl s 3 až 4 atómami uhlíka a/ /aleblo cykloailkyl s 3 až 6 atómami uhlíka a ich siolí. Tieto nlové látky sú významné účinné betalytika, použitelná pri léčbě róznych oběhových porúch. Vynález tiež chrání niekolko spósobov výroby látok obecného vzorca I.The invention relates to substituted aryloxypropanolamines of the general formula I OH OCH^HCH^NHR2 \Q^-NHCOOR (1')> where R1 is alkyl aleho/a alkyloxyl with 2 to 5 carbon atoms, pyrami or branched alkenyl with 2i to 5 carbon atoms aleho/a ethyloalkyl· with 3 to 6 carbon atoms and® is branched alkyl with 3 to 4 carbon atoms and/or cycloalkyl with 3 to 6 carbon atoms and their salts. These nil substances are important effective betalytics, useful in the treatment of various circulatory disorders. The invention also protects several methods of producing substances of general formula I.
Description
Vynález sa týká substituovaných arylo xypropanOlamínov všeobecného vzorca IThe invention relates to substituted aryl xypropaneolamines of general formula I
O-CHrCH-CH^NHfíO-CHrCH-CH^NHfí
nhcoor (I) kdenhcoor (I) where
R1 je priamy alebo rozvětvený alkyl alfetto alkoxyalkyl s 1 až 5 atómami uhlíka, priamy alebo rozvětvený alkenyl a 2 až 5 atómami uhlíka alebo cykloalkyl s 3 až 6 atómami uhlíka aR 1 is straight or branched alkyl alfetto alkoxyalkyl of 1 to 5 carbon atoms, straight or branched alkenyl of 2 to 5 carbon atoms or cycloalkyl of 3 to 6 carbon atoms and
R2 je rozvětvený alkyl s 3 až 4 atómami uhlíka alebo cykloalkyl s 3 až 6 atómami uhlíka.R 2 is branched alkyl of 3 to 4 carbon atoms or cycloalkyl of 3 to 6 carbon atoms.
Vynález sa týkia tiež solí substituovaných aryloxypropanolamínov všeobecného vzorca I, ako i spóšohov, ktorými možno uvedené látky připravovat.The invention also relates to salts of substituted aryloxypropanolamines of the general formula I, as well as to processes by which the said substances can be prepared.
Substituované aryloxypropanolamíny všeobecného vzorca I sú nové, v literatúre dioposial nepopísané zlůčeniny, ktoré vykazujú typické účinky betalytlk, podobné akio je tfoi u aryloxyprppanolamínov iným špósobom substituovaných (čs. pat. spis č. 128 471, americký pat, spis. č. 3 468 376, NSR pat. splS. č. 1 236 523, švajcarsky pat. spis. č. 451114 a 453 363). Všetky študované látky vykazujú antiizOprenailínovú, antiarytmickú a lokálně anestetickú aktivitu a účinky na tracheálny síval. Látky s pracovným označením BL-445 (příklad 31) a BL-443 (příklad 30) sú fairtoakiolioglcky ekvivalentně klinicky používanému metipranololu [1- (2,3,5-trimethyl-4-ace|toxyf enoxy) -3-izopropylamino-2-propanolu], taktiež možno předpokládat ich aplikáciu při terapii róznych porúch funkci® srdca a krvného oběhu. Účinnost látok padla vynálezu je uvedená v tabulke 1 — 3.Substituted aryloxypropanolamines of the general formula I are new compounds, not previously described in the literature, which exhibit typical betalytic effects, similar to those of aryloxypropanolamines substituted in other ways (Czech Pat. No. 128,471, American Pat. No. 3,468,376, German Federal Republic Pat. No. 1,236,523, Swiss Pat. Nos. 451,114 and 453,363). All studied substances exhibit antiisoprenaline, antiarrhythmic and locally anesthetic activity and effects on the tracheal mucosa. Substances with the working designation BL-445 (example 31) and BL-443 (example 30) are fairtoakiolioglcly equivalent to the clinically used metipranolol [1-(2,3,5-trimethyl-4-ace|toxy enoxy)-3-isopropylamino-2-propanol], it is also possible to assume their application in the therapy of various disorders of the function® of the heart and blood circulation. The effectiveness of the substances of the invention is shown in table 1-3.
Substituované aryloxyprapandlaraíny všeobecného vzorca I je možné pódia vynálezu připravit róznymi spóSobmi, napr. tak, že sa nechá reagovatSubstituted aryloxypropandlarains of general formula I can be prepared according to the invention by various methods, e.g. by letting it react
a) zlúčenina všeobecného vzorca IIa) a compound of general formula II
OHOlympic Games
II
O-CH^CH-CH-Ci (^-nhcoor4 (!/) márnym amíniom všeobecného vzorca NH2R2, v ktorom R2 znamená to isté ako· vo vzorciO-CH^CH-CH-Ci (^-nhcoor 4 (!/) a vain amine of the general formula NH2R 2 , in which R 2 means the same as in the formula
I.I.
b) zlúčenina všeobecného vzorca IIIb) a compound of general formula III
R1 znamená to isté akio vo vZorci I, s primárným amínom všeobecného vzorca NH2R2, v ktoriom R2 znamená to isté ako vo· vzorci I,R 1 means the same as in Formula I, with a primary amine of the general formula NH2R 2 , in which R 2 means the same as in Formula I,
c) zlúčehina všeobecného vzorca IVc) a compound of general formula IV
OH [04-NHCOOR4 v ktoromOH [04-NHCOOR 4 in which
R1 znamená to isté ako vo vzorci I s 1-alkylaminoi-2,3-epoxypriOpániom všeobecného· vzorca VR 1 has the same meaning as in formula I with a 1-alkylamino-2,3-epoxypropanium of the general formula V
CH.— CH-CH.-NHR \\Z ° IV) v ktoromCH.— CH-CH.-NHR \\Z ° IV) in which
R2 znamená to isté ako vo vzorci I, d) zlúčenina všeobecného vzorca IV v ktoromR 2 has the same meaning as in formula I, d) a compound of general formula IV in which
R1 znamená ta isté ako vo vzorci I, s 1 -alkylamino- 3-chlór-2-prOpanolbin všeobecného vzorca VIR 1 has the same meaning as in formula I, with 1-alkylamino-3-chloro-2-propanol of general formula VI
OHOlympic Games
II
Cl—CH2—CH—CH2—NHR2 (VI), v ktoriom v ktoromCl—CH2—CH—CH2—NHR2 (VI), in which in which
R1 znamená to isté akio vo vzorci I, s priR2 znamená to isté ako vo vzorci I.R 1 has the same meaning as in formula I, with R 2 having the same meaning as in formula I.
Pri přípravě podlá vynálezu prebieha re£20271 akcia medzi obidvotma východzími zložkami v prostředí alkoholu, alebo· Vody za katalytického posioibenla hydroxidu alkalického· kovu, například hydroxidu sodného,, huď při teplote miestnosti, alebo prii teplote bodu, varu reakčnej zmesy.In the preparation according to the invention, the reaction between the two starting components takes place in an alcohol or water environment under the catalytic action of an alkali metal hydroxide, for example sodium hydroxide, at room temperature or at the boiling point of the reaction mixture.
Po skončení reakcie sa reakčná zmes najčastejšie spracuje tak, že sa pretrepe zriedeným roztokom hydroxidu·, alkalického kovu, organické nazpúšťadlo oddestiluje: a odparek predstavujúci surový bazický ester sa přečistí převedením na sol', alkalizáciOu a extrakciiou do organického s vodou nemiešateťnéhio rloizpúš ťadla;After the reaction is complete, the reaction mixture is most often worked up by shaking it with a dilute solution of alkali metal hydroxide, distilling off the organic solvent; and the residue, representing the crude basic ester, is purified by conversion to a salt, alkalization, and extraction into an organic, water-immiscible solvent;
Z tohoto roztoku je možné bázický ester previesf pniamio na žiadanú slof a tú dalej čistit kryštailzáciou z vody,, organického rozpúšťadla, alebo zo zmesy organických rozpúšťadiel. Zo solí- s anorganickými· kyselinami vhodnými; pre přípravu aplikačných foriem prichádzajú v úvahu: hydrochliorid, hydrioibromid, síran, fosforečnan, připadne zo stolí s organickými kyselinami napr. šťavelan, vínan, maleinát, funiarát a iné.From this solution, the basic ester can be converted directly to the desired solution and further purified by crystallization from water, an organic solvent, or a mixture of organic solvents. Among the salts with inorganic acids suitable for the preparation of application forms, the following are suitable: hydrochloride, hydrobromide, sulfate, phosphate, and from the salts with organic acids, e.g. oxalate, tartrate, maleate, funiate, and others.
Podrobnosti· přípravy sú uvedené v nasledujúcich príkladoch prevedenia.Details of the preparation are given in the following design examples.
P r í k 1 a· d 1Example 1
Etyl-4 [ (2-hydroxy-3-cyklohexylamino)-propoxy ] karbanilátEthyl 4 [(2-hydroxy-3-cyclohexylamino)-propoxy]carbanilate
K roztoku 10,5 g (0,038 mol] etyl-4[ (2-hydroxy-3-chlór ) -propoxy J-karbanilátu v 50 ml metanolu sa přidá 4,9 g (0,05 mol) cyklohexylamínu a zahrieva sa 10 h v autokláve pri tepliote 110 °C.To a solution of 10.5 g (0.038 mol) of ethyl 4-[(2-hydroxy-3-chloro)-propoxy]-carbanilate in 50 ml of methanol is added 4.9 g (0.05 mol) of cyclohexylamine and heated for 10 h in an autoclave at 110 °C.
Po vychladnutí reakčnej zmesy sa· vakuová oddestiluje metanol a cyktobexylamín, odparek rozpustí v zriedenej kyselině chloroVodíkovej, pretrepe třikrát éterlom a z oddelenej vodnej fázy sa alkalizáciOu uvolní báza,, ktorá sas vytrepe doi éteru. Po vysušení bezvodým síranom horečnatým sa a filtrátu přidáním; éterického. roztoku suchého chlorovodíka vylúči hydrochlorid,, ktorý sa prekryštalizuje zto zmesy 2-propantol-éter (t. t. 156. až 159 °G.After the reaction mixture has cooled, methanol and cyclohexylamine are distilled off in vacuo, the residue is dissolved in dilute hydrochloric acid, shaken three times with ether, and the base is released from the separated aqueous phase by alkalization, which is shaken into ether. After drying with anhydrous magnesium sulfate, the filtrate is treated with an ethereal solution of dry hydrogen chloride to separate the hydrochloride, which is recrystallized from a 2-propanol-ether mixture (m.p. 156 to 159 °C).
Příklad 2Example 2
Propyl-2[ (2-hydroxy-3-izOpropylamino·)-pr opoxy ] kar bani látPropyl-2[(2-hydroxy-3-isopropylamino·)-propoxy]carbanilate
K roztoku 9,0 g (0,035 mol)· propyl-2( (2,,3-epoxy)-propoxy] karbanilátu v 30 ml 2-propanolu sa přidá 3,5 g (0,06 mol) iztoprtopylamínu a 2 ml; viody; Reakčná zmes sa zahrieva v autokláve pri teplote 100 °G 5 hi Po vychladnutí reakčnej: zmesy sa vákuovo oddestiluje rozpúšťadlo a přebytek izopropylamínu. Odparek sia· rozpustí v zriedenej kyselině chlorovodíkové], pretrepe třikrát éíberom a z oddelenej Vodnej fáze alkalizáciOu uvolní báza, ktorá sa vytrepe do·· éteru. Po vysušení bezvodým síranom horečnatým sa· z filtrátu přidáním.; éterického; roztoku suchého chlertevodíka, vylúči, hydrachltarid,,, ktorý sa prekryštalujp· zo· zmesy acetón-éter (t. 1.115 až 118 °C).To a solution of 9.0 g (0.035 mol) of propyl-2-((2,,3-epoxy)-propoxy] carbanilate in 30 ml of 2-propanol are added 3.5 g (0.06 mol) of isopropylamine and 2 ml of water. The reaction mixture is heated in an autoclave at 100 °C for 5 h. After the reaction mixture has cooled, the solvent and excess isopropylamine are distilled off in vacuo. The residue is dissolved in dilute hydrochloric acid, shaken three times with a whisk, and the base is released from the separated aqueous phase by alkalization, which is shaken into ether. After drying with anhydrous magnesium sulfate, the hydrate is separated from the filtrate by adding an ethereal solution of dry hydrogen chloride, which is recrystallized from an acetone-ether mixture (i.e. 1.115 to 118 °C).
Příklad 3Example 3
Izopropyl-3.[, (;2-hydr,Qxy‘-3-tere.butylamin|Oo)-propoxy ] karbaniilátIsopropyl-3.[, (;2-hydr , Nxy'-3-tere.butylamine|O )-propoxy ] carbanilate
12,4 g; (0,064 moll) izopropylestoru kyseliny 3-hydtaxykarhanitovej. a 8,3; g, (0,064 mol) 14erc.butylaminoi-2,3-epO'xypmpánu·. v 40 ml Vody a v 2 ml 42% roztoku hydrtoixidu sodného; sa mieša 6 h pri tepliote miestniosti., Giny· roztek sa. zLeje. a živičná zsaženina rozpustí; v zriedenej, kyselme, chlorovodíkovej, pnetcepe· tbikráts éterom a z oddelenej vodnej fáze alkalizáciOu uvolní báza, ktorá sa vytrepe do éteru. Po vysušení bezviodým.! sinaném horečnatým: z: filtrátu přidáním éterického. roztoku suchého chlorovodíka sa. vylúči hydrochlorid,, ktorý. sa prekryštalizuje zo· zmesy acetón-etanol (t. t. 136 — 138 °C).12.4 g ; (0.064 mol) isopropyl ester of 3-hydroxycarboxylic acid. and 8.3; g, (0.064 mol) 14-tert.butylamino-2,3-epoxypropane. in 40 ml of water and in 2 ml of 42% sodium hydroxide solution; are stirred for 6 h at room temperature., Giny· solution is. decanted. and the resinous precipitate is dissolved; in dilute, acidic, hydrochloric, pnetcepeti· tbicrats ether and from the separated aqueous phase alkalization releases the base, which is shaken into ether. After drying with lead-free.! magnesium cyanide: from: the filtrate by adding ethereal. solution of dry hydrogen chloride. hydrochloride is precipitated,, which. is recrystallized from an acetone-ethanol mixture (mp 136 — 138 °C).
P r í k 1 a di 4Example 4
Cyklohexyl-4:[i (2-hydroxy-3-izopropylamino) -propoxy ] karbanilátCyclohexyl-4:[i(2-hydroxy-3-isopropylamino)-propoxy]carbanilate
5,6 g (QjQ23t mol), cyklohexyleetenu kyseliny 4Ayddo|xykaribamÍavej',, 4$ g (0,023 mol) hydrochlloridu l-chlór-3-izopBopy<lamino-2-prtopanolu a 2,1 g hydroxidu sodného (0,054 mleli), v, 75> mi. etanolu sa zahrieva v zatavenej; trubici IQ h< pri teplote.· 1QQ °C. Z reakčnej zmesy sa« vákuovo, oddestiluje rozpúšťadlo· a zbytek sa suspenduje v 30. ml. 2N hydroxidu Sodného. Uvolněná báza sa vytrepe do éteru, a po vysušení bezvodým síranom horečnatým; ste z filtrátu přidáním éterického raatoto suchého· chlorovodíka vylúči hydrochlorid, ktorý sa prekryštalizuje Zoi zmesy acetón-éter (t. t. 151 až 153 °CJ.5.6 g (0.023 mol) of cyclohexylethylene of 4-hydroxycarbamide acid, 4.5 g (0.023 mol) of 1-chloro-3-isopropylamino-2-propanol hydrochloride and 2.1 g of sodium hydroxide (0.054 mol) in 75 ml of ethanol are heated in a sealed tube for 10 h at a temperature of 100 °C. The solvent is distilled off from the reaction mixture under vacuum and the residue is suspended in 30 ml of 2N sodium hydroxide. The liberated base is shaken out in ether and, after drying with anhydrous magnesium sulfate, The addition of ethereal solution of dry hydrogen chloride precipitates the hydrochloride from the filtrate, which is recrystallized from an acetone-ether mixture (m.p. 151 to 153 °C).
S použitím hone popísaných metod, holi připravené· tieto· nové látky (v zátvoirkách pracovné označenie·},:Using the methods described above, the following new substances (working designations in brackets) were prepared:
1. metyl-2[ (2-hydroxy-3-izopropylamino· )-prioipQxyjkarbaniláthydrochlorid,1. methyl-2[(2-hydroxy-3-isopropylamino· )-propyloxycarbanilate hydrochloride,
t. t. 125 až· 127-°G (acetémetanol);t. t. 125 to·127-°G (acetemethanol);
(BL-123),(BL-123),
2. metyl-2[ (;2-hydrloxy-3-terc.butylamino)-pnotpoxyjkarbaniláthydEOGhltorid',2. methyl-2[(;2-hydroxy-3-tert.butylamino)-pnotoxycarbanilate ethoxylated EOGhltorid',
t. t. 99 až 1S£°G (acefióu), (BJi-125-j:,t. t. 99 to 1S£°G (acefióu), (BJi-125-j:,
3. metyl-3[ (2-hydrtoxy-3-izopnopylamiao:·);-prlopoxy ] karbaniláthydr ochlorid,3. methyl-3[(2-hydroxy-3-isopnopylamiao:·);-prlopoxy]carbanilate hydrochloride,
1.1. lil· až 112; °C; (aceton?.). (^-133),,1.1. lil· to 112; °C; (acetone?.). (^-133),,
4. metyl-3[ (2-rhydaí0xy.--3!-terc.butylaminoi)-propoxy ] karbaniláthydr ochlorid,.4. Methyl-3[(2-hydroxy.--3'-tert.butylamino)-propoxy]carbanilate hydrochloride.
t. t, 163 až 167 °C (2i-pnopanol) (LB-135),t. t, 163 to 167 °C (2i-pnopanol) (LB-135),
5. metyl-4[ (2-hydr|oxy-3-izopropylammo)-prioipoxy ] karbaniláthydr ochlor id,5. methyl-4[(2-hydr|oxy-3-isopropylamino)-prioipoxy]carbanilate hydrochloride,
1.1. 160 až 163 °C (2-priopaniol-éter) BL-143),1.1. 160 to 163 °C (2-propanol ether) BL-143),
6. metyl-4[ (2-hydroxy-3-terc.butylamino)-prιopoxy]kaιrbaniláthydrochl©rid,6. methyl-4[(2-hydroxy-3-tert.butylamino)-propoxy]carbanilate hydrochloride,
1.1.156 až 158 °C (acetón-éter) (BL-145),1.1.156 to 158 °C (acetone-ether) (BL-145),
7. etyl-2i[: (2-hydrloxy-3-izopropylamino ) -priopoxy ] karbaniláthydrochítorid,7. ethyl-2i[ : (2-hydroxy-3-isopropylamino)-propoxy]carbanilate hydrochloride,
1.1.102 až 104 °C (acetón-petrolétier) (BL-223),1.1.102 to 104 °C (acetone-petroleum ether) (BL-223),
8. etyl-2[ (2-hydr|oxy-3-terc.buty lamino ]-propoxy ] karbanlláthydroohlorid,8. ethyl-2[(2-hydroxy-3-tert.butylamino]-propoxy]carbanlate hydrochloride,
1.1. 128 až 130 °C (acetón-éter) (BL-225),1.1. 128 to 130 °C (acetone-ether) (BL-225),
9. etyl-3[ (2-hydhoxy-3-izopropylamino)-pnopoxy ] karbaniláthydrochílorid,9. Ethyl-3[(2-hydoxy-3-isopropylamino)-pnooxy]carbanilate hydrochloride,
t.1. 104 až 105 °C (acetón-éter) (BL-233),mp 104 to 105 °C (acetone-ether) (BL-233),
10. etyl-3[ (2-hydroxy-3-terc.butylamino)-priopoxy ] kartíaniláthydrochllorid,10. ethyl-3[(2-hydroxy-3-tert.butylamino)-priopoxy]carthianilate hydrochloride,
t. t. 130 až 131 °C (etanol-éter) (BL-235),t. t. 130 to 131 °C (ethanol-ether) (BL-235),
11. etyl-4[ (2-hydroxy-3-izoprlopylaminio)-priopoxy ] karbanlláthydr ochlorid,11. ethyl-4[(2-hydroxy-3-isoprlopylaminio)-priopoxy]carbanlate hydrochloride,
1.1. 141 až 142: QC (2-propanol-éterj (BL-243),1.1. 141 to 142: Q C (2-propanol etherj (BL-243),
12. etyl-4[ (2-hydroxy-3-terc.butylamino)-propoxy ] kar bianiláthydrochlorid, t, t. 86 až 88 °C (acetón-éter ) (BL-245),12. ethyl-4[(2-hydroxy-3-tert.butylamino)-propoxy] carbonylate hydrochloride, mp 86 to 88 °C (acetone-ether) (BL-245),
13. propyl-2[ (2-hydrioxy-3-izopropylamin©)-prlopoxy ] karbianiláthydrochlorid,13. propyl-2[(2-hydroxy-3-isopropylamine©)-prlopoxy]carbanilate hydrochloride,
1.1. 115 až 118 °C (acetón-éter)1.1. 115 to 118 °C (acetone-ether)
BL-323),BL-323),
14. propyl-2i[ (2-hydroxy-3-terc.butyliamino)-priopoxy ] karhaniláthydrochlorid,14. propyl-2i[(2-hydroxy-3-tert.butyliamino)-priopoxy] carhanilate hydrochloride,
t. it. 123 až 131 °C (acetón-éter) (BL-325),mp 123 to 131 °C (acetone-ether) (BL-325),
15. propyl-3[ (2-hydrioxy-3-iZopropylamin©)-pnopoxy ] karhaniláthydrochlorid,15. propyl-3[(2-hydryoxy-3-isopropylamine©)-pnopoxy]carhanylate hydrochloride,
1.1. 94 až 95 °C (acetón-éter) (BL-333),1.1. 94 to 95 °C (acetone-ether) (BL-333),
16. pnopyl-3[ (2-hydrioxy-3-terc,butylamino )-priopoxy ] karibaniláthydrochlorid,16. pnopyl-3[(2-hydryoxy-3-tert,butylamino)-priopoxy]carbanilate hydrochloride,
1.1. 153 až 155 °C (acetón-éter) (BL-335),1.1. 153 to 155 °C (acetone-ether) (BL-335),
17. propyl-4[ (2-hydroxy-3-izapropylamin|o)-prlopoxy ] karbaniláthydrochlorid,17. propyl-4[(2-hydroxy-3-isopropylamino)-propyloxy]carbanilate hydrochloride,
1.1. 140 až 141 °C (acetón-éter) (BL-343),1.1. 140 to 141 °C (acetone-ether) (BL-343),
18. propyl-4[ (2-hydnoxy-3-terc.butylamlnio)-prtopioxy ] karhaniláthydrochlorid,18. propyl-4[(2-hydnoxy-3-tert.butylamino)-prtopioxy]carhanylate hydrochloride,
t. t. 76 až 77 °C acetón-éter ) (BL-345),mp 76 to 77 °C acetone-ether ) (BL-345),
19. izopr opyl-2 ((2i-hydroxy-3-izopropylamino) -pnoploxy] karibaniláthydrochlorid,19. isopropyl-2 ((2i-hydroxy-3-isopropylamino)-pnoploxy] caribanilate hydrochloride,
1.1. 111 až 113 °C (acetón) (BL-323izoi),1.1. 111 to 113 °C (acetone) (BL-323izoi),
20. iziopriopyl-2[ (2-hydroxy-3-terc.butylaminoi) -propoxy ] karbaniláthydrlochlorid,20. isopropyl-2[(2-hydroxy-3-tert.butylamino)-propoxy]carbanilate hydrochloride,
1.1. 154 až 157 °C (acetón-éter) (BL-izo325),1.1. 154 to 157 °C (acetone-ether) (BL-iso325),
21. izopr©pyl-2|[ (2-hydroxy-3-izobutylamiln©) -prlapoxyjkar bianiláthydrochlorid,21. isopropyl-2|[(2-hydroxy-3-isobutylamiln)-propyloxycar bianylate hydrochloride,
1.1. 149 až 152 °C (acetón-éter) (BL-izo324),1.1. 149 to 152 °C (acetone-ether) (BL-iso324),
22. izOpropyl-3[ (2-hydrOxy-3-iZopropylamino) -pnopoxy ] karblaniiáthydrochliorid,22. isopropyl-3[(2-hydroxy-3-isopropylamino)-pnooxy] carblaniate hydrochloride,
1.1. 108 až 110°C (acetón-éter) (BL-izo333),1.1. 108 to 110°C (acetone-ether) (BL-iso333),
23. izopropyl-3[ (a-hydnoxy-3-terc.butylamlnot)-propoxy ] karbaniláthydnochlorid,23. isopropyl-3[(α-hydroxy-3-tert.butylamino)-propoxy]carbanilate hydrogen chloride,
t. t. 136 až 138 °C (acetón-etanol] (BL-izo335),mp 136 to 138 °C (acetone-ethanol] (BL-iso335),
24. izoipr©pyl-4[ (2-hydrloxy-3-izlopr©pylamino ) -priopoxy ] karbaniláthydrochílorid,24. isopropyl-4[(2-hydroxy-3-isopropylamino)-propoxy]carbanilate hydrochloride,
t. t. 137 až 139 °C (acetón) (BL-ÍZ0343),mp 137 to 139 °C (acetone) (BL-ÍZ0343),
25. izopropyl-4[ (2-hydnoxy-3-terc.butylamimo·) -propoxy] karbaniláthydrochílorid,25. isopropyl-4[(2-hydnoxy-3-tert.butylamimo·)-propoxy]carbanilate hydrochloride,
t. t. 98 až 100 °C (acetón) (BL-izo345),mp 98 to 100 °C (acetone) (BL-iso345),
26. butyl-2 [ ( 2rhydroxy-3-iz©priOpylamino)-prlopioxy ] kiařfaaniláthydr ochlorid,26. butyl-2 [(2-hydroxy-3-isopropoxyamino)-propyl] phenylanilate hydrochloride,
t. t. 101 až 102 °C (acetón) (BL-423),mp 101 to 102 °C (acetone) (BL-423),
27. butyl-2[ (2-hydirioxy-3-.terc.butylaminoi)-prlopoxy ] karblaniiáthydrochliorid,27. Butyl-2[(2-hydroxy-3-.tert.butylamino)-propyloxy]carbalniate hydrochloride,
t. t. 138 až 140 °C (acetón-éter) (BL-425),mp 138 to 140 °C (acetone-ether) (BL-425),
28. butyl-3[ (2-,hydirιoxy-3-izιopropylamino)-pnopoxy] karbaniláthydr ochlorid,28. butyl-3[ (2- , hydiríoxy-3-isopropylamino)-pnopoxy] carbanilate hydrochloride,
t. t. 107 až 109 °C (acetón-éter) (BL-433),mp 107 to 109 °C (acetone-ether) (BL-433),
29. butyl-3[!(2-hydrOxy-3-terc.butylamino)-phopoxy ] karbaniláthy drochlor id,29. butyl-3[!(2-hydroxy-3-tert.butylamino)-phopoxy] carbanilathi drochlor id,
t. t. 140 až 144 °C (acetón-éter) (BL-435),mp 140 to 144 °C (acetone-ether) (BL-435),
30. butyl-4[ (2-hydroxy-3-.izopropylamin©)-prlopoxy ] karbianiláthydrochlorid,30. butyl-4[(2-hydroxy-3-.isopropylamine)-prlopoxy]carbanilate hydrochloride,
t. t. 124 až 126°C (acetón-éter) (BL-443),mp 124 to 126°C (acetone-ether) (BL-443),
31. butyl-4[i(i2rhydroxy-3-terc.bntylamino)-priopioxy ] karbaní 1'áthy drochlorid,31. Butyl-4-[i(12-hydroxy-3-tert.butylamino)-propioxy]carbaniol,
1.1. 150 až 155 °C (2-propanOl-éterj (BL-445),1.1. 150 to 155 °C (2-propaneol ether (BL-445),
32. pentenyl-2[ (2-hydroxy-3-iZopropylamino )-propoxy ] karhaniláthydroehlorid,32. pentenyl-2[ (2-hydroxy-3-isopropylamino)-propoxy] carhanylate hydrochloride,
t.1. 123 až 125 °C (acetón-etaniolj (BL-523),mp 123 to 125 °C (acetone-ethanol (BL-523),
33. pentyl-2(<( 2-hydr.oxy-3-terc.butylaininio)-propoxy ] kar bamiláthydr ochlorid,33. pentyl-2(<(2-hydr.oxy-3-tert.butylininio)-propoxy]carbamilate hydrochloride,
t. t. 148 až 150 °C (aceton) (BL-525),t. t. 148 to 150 °C (acetone) (BL-525),
34. pentyl-3[ (2-hydroxy-3-izopropylaminoj-propoxy ] karbaniláthydrochíorid,34. pentyl-3[(2-hydroxy-3-isopropylamino]-propoxy] carbanilate hydrochloride,
1.1. 118 až 120 °C (acetón-éter) (BL-533),1.1. 118 to 120 °C (acetone-ether) (BL-533),
35. pentyl-3[ (2-hydrloxy-3-terc.butylamino)-propoxy ] karbaniláthydrochíorid,35. pentyl-3[(2-hydroxy-3-tert.butylamino)-propoxy]carbanilate hydrochloride,
t. t. 135 až 138 °C (acetón-éter) (BL-535),mp 135 to 138 °C (acetone-ether) (BL-535),
36. penty 1-4 [ (2-hydroXy-3-izopr opy lamino)-propoxy ] karbaniláthydrochíorid,36. penty 1-4 [(2-hydroxy-3-isopropylamino)-propoxy]carbanilate hydrochloride,
1.t. 136 až 138 °C (acetón-petroléter) (BL-543),1.m. 136 to 138 °C (acetone-petroleum ether) (BL-543),
37. pentyl-4[ (2-hydroxy-3-terc.butylam.inoj- propoxy ] karbaniláthydrochíorid,37. pentyl-4[(2-hydroxy-3-tert.butylamino-propoxy]carbanilate hydrochloride,
1.1. 145 až 147°C (aceton-petrpléfer) (BL-545),1.1. 145 to 147°C (acetone-petroleum) (BL-545),
38. cyklohexyl-2[ (2-hydnoxy-3-iaopropylamimo)-propoxy ] karbíaniláthydriochlorid,38. cyclohexyl-2[(2-hydnoxy-3-iopropylamimo)-propoxy] carbianilate hydrochloride,
1.1. 147 až 150 °C (2-propanol-éter j (BL-623),1.1. 147 to 150 °C (2-propanol ether j (BL-623),
39. cyklohexyl-2í[ (2-hydrioxy-3-terc.butylamino) -pnopotxy JkarbaniTáthydnochliorid,39. cyclohexyl-2[(2-hydroxy-3-tert.butylamino)-pnopotoxy]carbaniTate chloride,
t. t. 192 až 195 °C (etanol-éter) (BL-625),t. t. 192 to 195 °C (ethanol-ether) (BL-625),
40. cykltoihexyl-3[ (i2!-hydroxy-3-izioprlapylamino) -propoxy) karbaniláthydrochíorid,40. cyclotohexyl-3[(12,1-hydroxy-3-isopropylamino)-propoxy)carbanilate hydrochloride,
1.1. 128 až 129 qC (acetón-éter) (BL-633),1.1. 128 to 129 ° C (acetone-ether) (BL-633),
41. cyklohexyl-3[ (2-hydroxy-3-terc.butylamino) -prlopoxy ] karbaniiláthydroichlorid, t. t. 138 až 140 aC (acetón-petroléter) (BL-635),41. cyclohexyl-3[(2-hydroxy-3-tert-butylamino)-propyloxy]carbanilate hydrochloride, mp 138-140 ° C (acetone-petroleum ether) (BL-635),
42. cyktohexyl-4[ (2-hydroxy-34zopropylamino) -propoxy ] karbaniláthydrochíorid, t. t. 151 až 153 °C (acetón-éter) (BL-643),42. cyclohexyl-4[(2-hydroxy-3-isopropylamino)-propoxy] carbanilate hydrochloride, m.p. 151 to 153 °C (acetone-ether) (BL-643),
43. etoxyetyl-2[ (2-hydroxy-3-izoprlopylamino) -propoxy ] karbaniláthydrochíorid, t. it. 102 až 105 °C (acetón-éter) (BL-723),43. ethoxyethyl-2[(2-hydroxy-3-isopropylamino)-propoxy] carbanilat hydrochloride, m.p. 102 to 105 °C (acetone-ether) (BL-723),
44. ettoxyetyl-2[ (2-hydroxy-3-terc.butylamino) -propioxy ] karbaniláthydrochíorid,44. ethoxyethyl-2[(2-hydroxy-3-tert.butylamino)-propiooxy]carbanilate hydrochloride,
1.1. 133 al 135 “C (2-propanol-éter) (BL-725),1.1. 133 al 135 “C (2-propanol-ether) (BL-725),
45. etoxyetyl-3[ (2-hydroxy-3-izopropylamimo) -propioxy ] karbaniláthydrochíorid,45. ethoxyethyl-3[(2-hydroxy-3-isopropylamino)-propioxy] carbanilate hydrochloride,
1.1. 147 až 150 °C (metanol-éter) (BL-733),1.1. 147 to 150 °C (methanol-ether) (BL-733),
46. etOxyetyl-3[ (2-hydnoxy-3-terc.butylamimo) -propioxy ] karbanilátfumarát, t. t. 143 al 146 °C (etanol-éter) (BL-735),46. ethOxyethyl-3[(2-hydnoxy-3-tert.butylamimo)-propioxy]carbanilate fumarate, t. t. 143 al 146 °C (ethanol-ether) (BL-735),
47. et'Oxyetyl-3 [ (2-hydroxy-3-izobutylamino) -propoxy ] karbaniláthydrochíorid,47. Et'Oxyethyl-3 [(2-hydroxy-3-isobutylamino)-propoxy]carbanilate hydrochloride,
t. t. 124 al 126 °C (acetón-éter ) (BL-734),t. t. 124 al 126 °C (acetone-ether) (BL-734),
48. etoxyetyl-4[ (2-hydroxy-3-izopropylaminio) -propoxy ] karbanilátfumarát,48. ethoxyethyl-4[(2-hydroxy-3-isopropylamino)-propoxy]carbanilate fumarate,
1.1. 175'al 178 °C (metanol-éter) (BL-743),1.1. 175'al 178 °C (methanol-ether) (BL-743),
49. etoxye:tyl-4[ (2-hydr oxy-3-terc.butylamíno>) -pr oploxy ] karbanilátfumarát, t. t. 177 až 179 °C (metanol-éter) (BL-745),49. ethoxyethyl-4[(2-hydroxy-3-tert-butylamino)-propoxy]carbanilate fumarate, m.p. 177 to 179 °C (methanol-ether) (BL-745),
50. etoxyetyl-4[ (2-hydroxy-3-izobutyla.mino j -propoxy ] karbaniláthydrochíorid,50. ethoxyethyl-4[(2-hydroxy-3-isobutylamino-propoxy]carbanilate hydrochloride,
1.1. 158 al 160 °C (acetén-etanolj (BL-744),1.1. 158 and 160 °C (acetene-ethanolj (BL-744),
51. etoxyetyl-2[ (2-hydroxy-3-iziobutylaminioj -prlopoxy] karbanilátioxalát,51. ethoxyethyl-2[(2-hydroxy-3-isobutylamino-propyloxy]carbanylthiooxalate,
t. t. 138 až 143 °C (etanol-éter) (BL-724),t. t. 138 to 143 °C (ethanol-ether) (BL-724),
52. alyl-2[ (2-hydroxy-3-izobutylaminioj- propoxy ] karbamiláthydr ochlorid, . t. t. 119 až 121 °C (acetón-petroléter) (BL-323),52. Allyl-2[(2-hydroxy-3-isobutylaminoj-propoxy]carbamylate hydrochloride, . m.p. 119 to 121 °C (acetone-petroleum ether) (BL-323),
53. alyl-2[ (2-hydroxy-34erc..butylamino)-propoxy ] karbaniláthydrochíorid,53. allyl-2[(2-hydroxy-34-tert..butylamino)-propoxy]carbanilate hydrochloride,
t. t. 166 až 168 °C (2-propanol-éterj (BL-325)t. t. 166 to 168 °C (2-propanol etherj (BL-325)
54. etyl-4 [ 2-hydr oxy-3-cyklopropylaminio) -propoxy ] karbaniláthydrochíorid,54. ethyl-4 [2-hydroxy-3-cyclopropylamino)-propoxy]carbanilate hydrochloride,
t. t. 156 až 160 °C (acetón-etaniolj (BL-246),mp 156 to 160 °C (acetone-ethanol (BL-246),
55. etyl-4[ (2-hy droxy-3-cyklopenty lamino)-propoxy ] karhaniláthydroehlorid,55. Ethyl-4[(2-hydroxy-3-cyclopentylamino)-propoxy]carhanylate hydrochloride,
t. t. 152 až 155 °C (2-propanol-éter) (BL-248),t. t. 152 to 155 °C (2-propanol ether) (BL-248),
56. etyl-2[ (2-hydrioxy-3-cyklohexylamlnoj-propoxy] kar hanlláthydrochlior id,56. ethyl-2[(2-hydroxy-3-cyclohexylamino-propoxy] carbonate hydrochloride,
t. t. 156 až 159 °C (2-propanol-éterj (BL-249),t. t. 156 to 159 °C (2-propanol-etherj (BL-249),
57. etyl-3[ (2-hydrtoxy-3-cyklobexylamlnoj-propoxy ] kar banlláthydr ochllorid, 't. t. 157 až 160 °C (2-propanol-éterj (BL-239),57. Ethyl-3[(2-hydroxy-3-cyclobexylpropoxy]carbonate hydrochloride, m.p. 157 to 160 °C (2-propanol ether (BL-239),
2'2ΌΖ'7Γ2'2ΌΖ'7Γ
TTabuh-řfeai 1TTabuh-řfeai 1
Efekt testovaných. látok a metípranololu. v kane. 10 mg/20 mb na. Izoprenalínom indukovaná tachykardiu na izolované predsiene morčiat.Effect of tested substances and metipranolol in can. 10 mg/20 mb on isoprenaline-induced tachycardia in isolated guinea pig atria.
Látka % zníženia TF po láitke % redukcle pozitivně chrionotr.Substance % reduction of TF after the test % reduction positive chryonotr.
úč. IP' po» lWbke vzhíádfom Ife kontrol, hodtiotám·account IP' after lWbke with regard to Ife controls, qualities
Tabulka1 2.Table 1 2.
Ochranný efekt- látok a metípranololu v· dávke 1 mg . kg-1 i; v: vyjadrenef spotřebouakonitinu pri indukcii arytmii, fibrilácii a letálnej zástavy srdca u anestezovanýcfr morčiat.Protective effect of metipranolol at a dose of 1 mg kg -1 on aconitine consumption during induction of arrhythmia, fibrillation and lethal cardiac arrest in anesthetized guinea pigs.
T a b u 1' k a 3Table 1' and 3
Akútna toxicita látok po s. c. aplikácii 1% roztoku myšiam.Acute toxicity of substances after s. c. application of 1% solution to mice.
Látka LDso (Mg. kg-1]Substance LD50 (Mg. kg -1 ]
Lokálně anestetická aktivitaLocal anesthetic activity
LátkaFabric
Index účinnosti LDso/mg .kg-1 povrchová anestézía infiltračná anestéziaEfficacy index LD50/mg.kg -1 superficial anesthesia infiltration anesthesia
2,02.0
1,0 <11.0 <1
1,01.0
2,22.2
1,01.0
4,04.0
7,07.0
4,44.4
4,24.2
1,0 <11.0 <1
7.7 =57.7 =5
4,2 =24.2 =2
3,63.6
5.85.8
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CS617681A CS220271B1 (en) | 1981-08-18 | 1981-08-18 | Substituted aryloxypropanolamines, salts and their production |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CS617681A CS220271B1 (en) | 1981-08-18 | 1981-08-18 | Substituted aryloxypropanolamines, salts and their production |
Publications (1)
Publication Number | Publication Date |
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CS220271B1 true CS220271B1 (en) | 1983-03-25 |
Family
ID=5408191
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CS617681A CS220271B1 (en) | 1981-08-18 | 1981-08-18 | Substituted aryloxypropanolamines, salts and their production |
Country Status (1)
Country | Link |
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CS (1) | CS220271B1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0302694A3 (en) * | 1987-08-05 | 1989-08-02 | Slovenska Akademia Vied | Substituted aryloxyamino-propanols and methods of preparing same |
-
1981
- 1981-08-18 CS CS617681A patent/CS220271B1/en unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0302694A3 (en) * | 1987-08-05 | 1989-08-02 | Slovenska Akademia Vied | Substituted aryloxyamino-propanols and methods of preparing same |
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