CS233086B1 - N-(1-(2-thienyl)ethyl)-3,3-diphenylpropylamin and method of its preparation - Google Patents
N-(1-(2-thienyl)ethyl)-3,3-diphenylpropylamin and method of its preparation Download PDFInfo
- Publication number
- CS233086B1 CS233086B1 CS400383A CS400383A CS233086B1 CS 233086 B1 CS233086 B1 CS 233086B1 CS 400383 A CS400383 A CS 400383A CS 400383 A CS400383 A CS 400383A CS 233086 B1 CS233086 B1 CS 233086B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- thienyl
- formula
- ethyl
- ethylamine
- diphenylpropylamine
- Prior art date
Links
- ZWBJXZKAKNVRLA-UHFFFAOYSA-N 3,3-diphenyl-n-(1-thiophen-2-ylethyl)propan-1-amine Chemical compound C=1C=CSC=1C(C)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 ZWBJXZKAKNVRLA-UHFFFAOYSA-N 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims abstract description 6
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- -1 salts acids Chemical class 0.000 claims abstract description 8
- LYJBVRVJQXVVPI-UHFFFAOYSA-N 1-thiophen-2-ylethanamine Chemical compound CC(N)C1=CC=CS1 LYJBVRVJQXVVPI-UHFFFAOYSA-N 0.000 claims abstract description 6
- UYXDQUAGGZJICS-UHFFFAOYSA-N 3,3-diphenylpropanoyl chloride Chemical compound C=1C=CC=CC=1C(CC(=O)Cl)C1=CC=CC=C1 UYXDQUAGGZJICS-UHFFFAOYSA-N 0.000 claims abstract description 4
- 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 abstract description 4
- 150000004645 aluminates Chemical class 0.000 claims abstract description 4
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 4
- 239000011734 sodium Substances 0.000 claims abstract description 4
- 150000001408 amides Chemical class 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 238000006386 neutralization reaction Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 9
- 241001465754 Metazoa Species 0.000 abstract description 6
- 239000002253 acid Substances 0.000 abstract description 2
- 239000003218 coronary vasodilator agent Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 230000010933 acylation Effects 0.000 abstract 1
- 238000005917 acylation reaction Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- NMKSAYKQLCHXDK-UHFFFAOYSA-N 3,3-diphenyl-N-(1-phenylethyl)-1-propanamine Chemical compound C=1C=CC=CC=1C(C)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 NMKSAYKQLCHXDK-UHFFFAOYSA-N 0.000 description 3
- VRPNHUNJQKJRPA-UHFFFAOYSA-N 3,3-diphenyl-n-(1-thiophen-2-ylethyl)propanamide Chemical compound C=1C=CSC=1C(C)NC(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 VRPNHUNJQKJRPA-UHFFFAOYSA-N 0.000 description 3
- 229960002602 fendiline Drugs 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- BZQGAPWJKAYCHR-UHFFFAOYSA-N 3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C(CC(=O)O)C1=CC=CC=C1 BZQGAPWJKAYCHR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- GVYJETXPYUZKIA-UHFFFAOYSA-N 3,3-diphenyl-n-(1-thiophen-2-ylethyl)propan-1-amine;hydrochloride Chemical compound Cl.C=1C=CSC=1C(C)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 GVYJETXPYUZKIA-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 241000699670 Mus sp. Species 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 231100000460 acute oral toxicity Toxicity 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Abstract
Předmětem vynálezu je N-/l-(2-thienyl)ethyl/-3,3-difenylpropylamin vzorce I jeho adiční soli s anorganickými a organickými kyselinami a způsob jeho přípravy spočívající v acylaci l-(2-thienyl) ethylaminu 3,3-difenylpropionylchloridem a redukcí získaného amidu vzorce II natriumdihydridobis(2-methoxyethoxy) aluminátem. Látka vzorce I vykazuje při farmakologických testech na zvířatech kardionrotektivní a koronárně vasodilatační účinky.The present invention provides N- [1- (2-thienyl) ethyl] -3,3-diphenylpropylamine of formula I, its inorganic and organic addition salts acids and the process for its preparation consisting of acylation of 1- (2-thienyl) ethylamine with 3,3-diphenylpropionyl chloride and reduction of the obtained amide of formula II with sodium dihydridobis (2-methoxyethoxy) aluminate. The compound of Formula I exhibits pharmacological properties animal tests are cardirotective and coronary vasodilator effects.
Description
Vynález se týká N-/1-(2-thieny1)ethy1/-3,3-difenylpropy1- aminu vzorce IThe present invention relates to N- [1- (2-thienyl) ethyl] -3,3-diphenylpropyl-amine of formula I
CH. I ,-NH-CH.CH. I, -NH-CH.
(I) jeho adičních solí s Farmaceuticky nezávadnými anorganickými a organickými kyselinami a způsobu jeho přípravy.(I) its addition salts with pharmaceutically acceptable inorganic and organic acids and a process for its preparation.
Látka vzorce I je thiofenovým analogem koronárního vasodilatancia a antagonisty kalcia fendilinu ( N-(1-fenylethy1)-3,3-difenylpropylaminu), který se klinicky používá při léčení ischemické srdeční choroby. Ve srovnání s fendilínem vykazuje látka vzorce I při farmakologických testech na zvířatech vyšší aktivitu, Například při zátěžovém testu na křečcícti s myokardem poškozeným aplikací isoprena1 i nu, při kterém se měří čas, po který vydrží testovaná zvířata plavat ve srovnání s nepremedikowanými zvířaty a kontrolní skupinou zvířat, prodlužuje aplikace látky vzorce I v perorální dávce 70 mg/kg v intervalu 1 až. 4 • hodiny před vlastní zátěží dobu plavání testovaných zvířat na úroveň doby naměřené u kontrolní, zdravé skupiny zvířat. Fendilin je v tomto testu účinný až v dávce 180 mg/kg p.o, Akutní perorální toxicita látky vzorce I na myších je jen málo vyšší než toxicita Fendilinu. Tyto výsledky naznačují, že látka vzorce I může nalézt uplatnění při léčení ischemické choroby srdeční u lidí.The compound of formula I is a thiophene analog of coronary vasodilator and fendilin calcium (N- (1-phenylethyl) -3,3-diphenylpropylamine) antagonist, which is clinically used in the treatment of ischemic heart disease. Compared to fendilin, the compound of formula I exhibits a higher activity in animal pharmacological tests, for example, in an isoprene-injured myocardial hamster stress test which measures the time the test animals can swim compared to non-medicated animals and the control group. administration of the compound of Formula I at an oral dose of 70 mg / kg at an interval of 1 to 20 mg / kg. • hours before exercise, the swimming time of the test animals to the level of the time measured in the control, healthy group of animals. The acute oral toxicity of the compound of formula I in mice is only slightly higher than that of Fendilin. These results indicate that the compound of Formula I may find utility in the treatment of ischemic heart disease in humans.
Vynález se týká též způsobu přípravy látky vzorce I. Podle vynálezu se látka vzorce I připraví dvoustupňovou syntézou vycházející ze známé kyseliny 3,3-difenylpropionové (3,F,3.The invention also relates to a process for the preparation of a compound of formula I. According to the invention, a compound of formula I is prepared by a two-step synthesis starting from the known 3,3-diphenylpropionic acid (3, F, 3.
Dippy a 3,T. Young, □. Chem. Soc. 1952, 1817) a známéhoDippy and 3, T. Young, □. Chem. Soc. 1952, 1817) and known
233 086233 086
1-(2-thienyl)ethylaminu (F.F. Blicke a 3.A. Burckhalter, 3,1- (2-thienyl) ethylamine (F.F. Blicke and 3.A. Burckhalter, 3,
Am, Chem. Soc, 64, 477, 1947). l-(2-Thienyl)ethylamin se acylu je v prvním stupni reaktivním derivátem kyseliny 3,3-difenylpro pionové, s výhodou 3,3-difenylpropionylchloridem v inertním organickém rozpouštědle, například v benzenu nebo toluenu, za přítomnosti činidla schopného vázat při reakci vznikající chlorovodík, například uhličitanů alkalických kovů nebo terciárních aminů, s výhodou triethylaminu. Získaný amid vzorce IIAm, Chem. Soc., 64, 477 (1947). 1- (2-Thienyl) ethylamine with acyl is in the first step a reactive derivative of 3,3-diphenylpropionic acid, preferably 3,3-diphenylpropionyl chloride in an inert organic solvent, for example benzene or toluene, in the presence of a reagent capable of binding in the reaction hydrogen chloride, for example alkali metal carbonates or tertiary amines, preferably triethylamine. The amide of formula II obtained
(11) se redukuje komplexními hydridy kovů. Pro tuto redukci se může použít lithiumaluminiumhydrid nebo natriumaluminiumhydrid v etheru nebo tetrahydrofuranu anebo zvláště vhodný natriumdihydridobis(2-methoxyethoxy)aluminát v benzenu nebo toluenu. Po . rozkladu reakční směsi vodným roztokem hydroxidu sodného a oddělení anorganických složek se báze látky vzorce I izoluje oddestilováním rozpouštědla a převedením na krystalickou sůl s anorganickou nebo organickou kyselinou, s výhodou na hydrochlor i d .(11) is reduced by complex metal hydrides. For this reduction, lithium aluminum hydride or sodium aluminum hydride in ether or tetrahydrofuran or a particularly suitable sodium dihydridobis (2-methoxyethoxy) aluminate in benzene or toluene may be used. Mon. decomposing the reaction mixture with an aqueous sodium hydroxide solution and separating the inorganic components from the base of the compound of formula I is isolated by distilling off the solvent and converting it into a crystalline salt with an inorganic or organic acid, preferably hydrochloride.
Podrobnosti způsobu přípravy podle vynálezu jsou uvedeny v následujících příkladech provedení, které však rozsah vynálezu v žádném směru neomezují.The details of the preparation process according to the invention are given in the following non-limiting examples.
Příklad 1Example 1
N-(3,3-di fenylpropiony1)-1-(2-thienyl)ethylaminN- (3,3-diphenylpropionyl) -1- (2-thienyl) ethylamine
K roztoku 12,7 g 1-(2-thienyl)ethylaminu a 11 g triethylaminu v 270 ml suchého toluenu se za chlazení na teplotu pod 10 °C přikape roztok 24,4 g 3,3-difenylpropionylchloridu (připraveného z 23 g kyseliny 3,3-difenylpropionové a 85 g thionylchloridu zahříváním 1 h v lázni teplé 90 °C a odpařením směsi za sníženého tlaku) ve 130 ml suchého toluenu během 20 minut. Chladící lázeň se odstraní a za neustálého míchání se nechá teplota reakční směsi vystoupit na teplotu místnosti. Směs se ponechá v klidu při teplotě místnosti 12 h, přičemž z roztoku vykrystaluje většina produktu. Po rozmíchání se 100 ml vodyTo a solution of 12.7 g of 1- (2-thienyl) ethylamine and 11 g of triethylamine in 270 ml of dry toluene is added dropwise a solution of 24.4 g of 3,3-diphenylpropionyl chloride (prepared from 23 g of acid 3) while cooling to below 10 ° C. 3-diphenylpropionic and 85 g of thionyl chloride by heating in a bath at 90 ° C for 1 h and evaporating the mixture under reduced pressure) in 130 ml of dry toluene for 20 minutes. Remove the cooling bath and allow the reaction mixture to reach room temperature while stirring. The mixture is allowed to stand at room temperature for 12 h, with most of the product crystallizing out of solution. After mixing with 100 ml of water
233 086 se odsaje 19,1 g produktu. Z filtrátu se získá druhý podíl oddělením toluenové vrstvy, promytím 25% vodným amoniakem, vodou, 10% kyselinou chlorovodíkovou a vodou, vysušením bezvodým síranem horečnatým a zahuštěním na odparce za sníženého tlaku na ob jem asi 150 ml. Ochlazením vykrystaluje dalších 6,8 g produktu. Spojené podíly (25,9 g, 77,3 % teorie) se rozpustí ve 150 ml vroucího ethanolu a roztok se za tepla zfiltruje s aktivním uhlím. Z filtrátu vykrystaluje 22,8 g čistého N-(3,3-difenylpropionyl)-l~(2-thienyl)ethylaminu s t.t. 147 až 148 °C, a233.1 g of product are suctioned off. A second crop was obtained from the filtrate by separating the toluene layer, washing with 25% aqueous ammonia, water, 10% hydrochloric acid and water, drying over anhydrous magnesium sulfate, and concentrating under reduced pressure to a volume of about 150 ml. An additional 6.8 g of product crystallized by cooling. The combined fractions (25.9 g, 77.3% of theory) were dissolved in boiling ethanol (150 mL) and the solution was hot filtered with charcoal. 22.8 g of pure N- (3,3-diphenylpropionyl) -1- (2-thienyl) ethylamine, m.p. 147-148 ° C; and
. Příklad 2 t N-/l-(2-thienyl)ethyl/-3,3-difenylpropylamin. Example 2 1 N- (1- (2-thienyl) ethyl) -3,3-diphenylpropylamine
Ke 22 g N-(3,3-difenylpropionyl)-l-(2-thienyl)ethylaminu ve 140 ml suchého benzenu se přikape za míchání a chlazení na teplotu 20 °C 75,6 ml 70% roztoku natriumdihydridobis(2-methoxyethoxy)aluminátu v toluenu během 20 minut. Reakční směs se míchá při teplotě místnosti 10 h načež se za míchání zahřívá k va ru 3 h. Po ochlazení se k míchané reakční směsi opatrně přikape 92 ml 10% roztoku hydroxidu sodného, přičemž se teplota směsi udržuje chlazením vodou a ledem pod 30 °C. Organická vrstva se zředí přidáním etheru, oddělí se, promyje 4% vodným roztokem hydroxidu sodného, vodou, nasyceným roztokem chloridu sodného, vysuší se bezvodým síranem sodným a rozpouštědla se oddestilují za sníženého tlaku. Získaná olejovitá báze produktu (23,8 g) se pňwede na krystalický hydrochlorid rozpuštěním v isopropylalkoholu a okyselením roztokem chlorovodíku v etheru. Získá seTo 22 g of N- (3,3-diphenylpropionyl) -1- (2-thienyl) ethylamine in 140 ml dry benzene was added dropwise with stirring and cooling to 20 ° C 75.6 ml of a 70% solution of sodium dihydridobis (2-methoxyethoxy) of aluminate in toluene over 20 minutes. The reaction mixture was stirred at room temperature for 10 h and then heated to boiling for 3 h with stirring. After cooling, 92 ml of 10% sodium hydroxide solution was carefully added dropwise to the stirred reaction mixture, keeping the temperature of the mixture below 30 ° C. . The organic layer was diluted with ether, separated, washed with 4% aqueous sodium hydroxide solution, water, saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvents were distilled off under reduced pressure. The obtained oily base of the product (23.8 g) was converted to the crystalline hydrochloride by dissolving in isopropyl alcohol and acidifying with a solution of hydrogen chloride in ether. It is obtained
17,3 g (73,7 % teorie) hydrochloridu N-/l-(2-thienyl)ethyl/-3,3-difenylpropylaminu s t.t, 172 až 175 °C. Analyticky čistá ’ látka taje při 177 až 179 °C (isopropylalkohol).17.3 g (73.7% of theory) of N- [1- (2-thienyl) ethyl] -3,3-diphenylpropylamine hydrochloride, m.p. 172-175 ° C. An analytically pure substance melts at 177-179 ° C (isopropyl alcohol).
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS400383A CS233086B1 (en) | 1983-06-02 | 1983-06-02 | N-(1-(2-thienyl)ethyl)-3,3-diphenylpropylamin and method of its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS400383A CS233086B1 (en) | 1983-06-02 | 1983-06-02 | N-(1-(2-thienyl)ethyl)-3,3-diphenylpropylamin and method of its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS233086B1 true CS233086B1 (en) | 1985-02-14 |
Family
ID=5381762
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS400383A CS233086B1 (en) | 1983-06-02 | 1983-06-02 | N-(1-(2-thienyl)ethyl)-3,3-diphenylpropylamin and method of its preparation |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS233086B1 (en) |
-
1983
- 1983-06-02 CS CS400383A patent/CS233086B1/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0178874B1 (en) | Alkylsulfonamidophenylalkylamines | |
| EP0474561B1 (en) | Arylalkylamines, process for their preparation and pharmaceutical compositions containing them | |
| JP2655692B2 (en) | Sulfonamidothienylcarboxylic acid compound | |
| EP0373998B1 (en) | Propenone oxime ethers, method for their preparation and pharmaceutical compositions containing them | |
| DE3700408A1 (en) | Indole derivatives, pharmaceutical preparations containing them and processes for their preparation | |
| CH618425A5 (en) | ||
| DE69605856T2 (en) | Alkoxyaryl compounds with affinity for melatonin receptors, processes for their preparation and pharmaceutical compositions containing them | |
| SI9012429A (en) | New chroman and thiochroman derivatives | |
| JPS63277661A (en) | Piperidine opioid antagonist | |
| CA2024581A1 (en) | Substituted n-benzylpiperidine amides | |
| WO2007042668A1 (en) | Derivatives of 1-amino-isoquinoline, preparation method thereof and use of same in therapeutics in the treatment of a dysfunction associated with mch receptor 1 | |
| JPS6147838B2 (en) | ||
| CS226183B2 (en) | Method of preparing n-ethyl-2-(2,6-dialkoxybenzamidomethyl)-pyrrolidine derivatives | |
| DE69605975T2 (en) | Arylalkyl (thio) carboxamide compounds with affinity for melatonin receptors, processes for their preparation and pharmaceutical compositions containing them | |
| DE3719699A1 (en) | INDOLDER DERIVATIVES | |
| CH642348A5 (en) | ALKYLTHIOPHENOXYALKYLAMINE. | |
| BG99253A (en) | Epi - epibatydine derivatives | |
| CS233086B1 (en) | N-(1-(2-thienyl)ethyl)-3,3-diphenylpropylamin and method of its preparation | |
| EP0443918A1 (en) | Derivatives of 20,21-dinoreburnamenine, process for their preparation and intermediates, their use as medicines and compositions containing them | |
| US5070094A (en) | N-benzyltropaneamides | |
| DE69111541T2 (en) | New indole and indoline compounds. | |
| EP0384843A2 (en) | 1-Arylsulfonyl-2-piperidinone derivatives, process and intermediates for their preparation, their pharmaceutical use and compositions containing them | |
| KR910010081B1 (en) | Process for preparation of nitrovicaminic acid derivatives | |
| US5053413A (en) | N-benzylpiperidineisoindolinones | |
| EP0275762B1 (en) | Indole carboxamide derivatives and their salts, process and intermediates for their preparation, their use as medicines and compositions containing them |