CS213322B2 - Method of making the new derivatives of n-/3,3-diphenylpropyl/-propylendiamine - Google Patents
Method of making the new derivatives of n-/3,3-diphenylpropyl/-propylendiamine Download PDFInfo
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- CS213322B2 CS213322B2 CS787722A CS772278A CS213322B2 CS 213322 B2 CS213322 B2 CS 213322B2 CS 787722 A CS787722 A CS 787722A CS 772278 A CS772278 A CS 772278A CS 213322 B2 CS213322 B2 CS 213322B2
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- Prior art keywords
- compound
- phenyl
- prenylamine
- propyl
- formula
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- 238000004519 manufacturing process Methods 0.000 title claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 11
- -1 3,3-diphenylpropyl Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- IFFPICMESYHZPQ-UHFFFAOYSA-N Prenylamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)CCNC(C)CC1=CC=CC=C1 IFFPICMESYHZPQ-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 229960001989 prenylamine Drugs 0.000 claims description 7
- 125000004345 1-phenyl-2-propyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 238000009835 boiling Methods 0.000 claims description 3
- 229940125890 compound Ia Drugs 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papavarine Natural products C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 239000012279 sodium borohydride Substances 0.000 claims description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- QBIAZVPERXOGAL-OWOJBTEDSA-N (e)-prop-1-ene-1,3-diamine Chemical compound NC\C=C\N QBIAZVPERXOGAL-OWOJBTEDSA-N 0.000 claims description 2
- BYNJCCMGUBTMJZ-UHFFFAOYSA-N 3,3-diphenylpropanal Chemical compound C=1C=CC=CC=1C(CC=O)C1=CC=CC=C1 BYNJCCMGUBTMJZ-UHFFFAOYSA-N 0.000 claims description 2
- 229930008281 A03AD01 - Papaverine Natural products 0.000 claims description 2
- 229910000761 Aluminium amalgam Inorganic materials 0.000 claims description 2
- 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
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 150000004985 diamines Chemical class 0.000 claims description 2
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229910052759 nickel Inorganic materials 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 229960001789 papaverine Drugs 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 235000019441 ethanol Nutrition 0.000 claims 4
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 claims 2
- 238000009833 condensation Methods 0.000 claims 2
- 230000005494 condensation Effects 0.000 claims 2
- HMMWEJUBAXMERM-UHFFFAOYSA-N 2,2-diphenylpropanal Chemical compound C=1C=CC=CC=1C(C=O)(C)C1=CC=CC=C1 HMMWEJUBAXMERM-UHFFFAOYSA-N 0.000 claims 1
- MUCUZLKILOOHBH-UHFFFAOYSA-N C=1C=CC=CC=1C(CCNCC(N)C)C1=CC=CC=C1 Chemical class C=1C=CC=CC=1C(CCNCC(N)C)C1=CC=CC=C1 MUCUZLKILOOHBH-UHFFFAOYSA-N 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 claims 1
- 230000003288 anthiarrhythmic effect Effects 0.000 claims 1
- 230000004397 blinking Effects 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 230000000052 comparative effect Effects 0.000 claims 1
- 210000004087 cornea Anatomy 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 230000009931 harmful effect Effects 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 231100000636 lethal dose Toxicity 0.000 claims 1
- 230000003389 potentiating effect Effects 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000004351 coronary vessel Anatomy 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 235000019687 Lamb Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 150000002238 fumaric acids Chemical class 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- NRRFWAJFWHFQGN-UHFFFAOYSA-N n'-(1-phenylpropan-2-yl)propane-1,3-diamine Chemical compound NCCCNC(C)CC1=CC=CC=C1 NRRFWAJFWHFQGN-UHFFFAOYSA-N 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical class CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
ČESKOSLOVENSKAÍÓfclAilSnCKAli 6 ř U B l ! K SH9) POPtS VYNÁLEZU K PATENTU 213322 (lij jii) (22) Přihlášeno 24 04 73(21) (PV 7722-78) (51) Int. Cl.5 C 07 C 85/08 11¾ (32 ) (31) (33) Právo přednosti od 24 04 72(01-1226) Maďarská lidová republika OftAD PRO VYNÁLEZY; A OBJEVY (40) Zveřejněno 31 07 81 (45) Vydáno 15 08 84 (72) ,..CZECHOSLOVENSKAIÓfclAilSnCKAli 6 ø U B l! SH9) POPTS OF THE INVENTION 213322 (lij jii) (22) Registered 24 04 73 (21) (PV 7722-78) (51) Int. Cl.5 C 07 C 85/08 11¾ (32) (31) (33) Priority from 24 04 72 (01-1226) Hungarian People's Republic OftAD FOR INVENTIONS; AND DISCOVERY (40) Published 31 07 81 (45) Published 15 08 84 (72), ..
Autor vynálezu KORBONITS DEZŠO dr., HARSÁNYI KÁLMÁN dr„ LESZKOVSZKY GYORGY dr., BUDAPEŠŤ, MOLŇÁR ERZSÉBET dr., SZODLIGET (MLR) (73) ·.........................Author of the invention KORBONITS DEZŠO dr., HARSÁNYI KÁLMÁN dr "LESZKOVSZKY GYORGY dr., BUDAPEST, MOLŇÁR ERZSÉBET dr., SZODLIGET (MLR) (73) · ................... ......
Majitel patentu CHINOIN GYŮGYSZER ÉS VĚGĚYÉSŽETL TÉRMÉKÉK GÝÁRA RT.,BUDAPEŠŤ (MLR) (54) Způsob výroby nových derivátů N-(3,3-tíífenylpropyljpropylendiaminuPatent holder CHINOIN GYŮGYSZER ÉS VĚGĚYÉSŽETL TÉRMÉKÉK GÝÁRA RT., BUDAPEST (MLR) (54) Method for the production of new N- (3,3-thienyl-propyl-propylenediamine derivatives)
XX
Vynález se týká způsobu výroby novýchderivátů N- (3,3-difenylpropylJpropylendiami-nu jakož i jejich solí s terapeuticky vhodný-mi vlastnostmi, jež jsou v prvé řádě použitel-né při srdečních chorobách jako léčiva zvy-šující průtok krve v koronárních cévách ajako antirytmická léčiva.BACKGROUND OF THE INVENTION The present invention relates to a process for the preparation of novel N- (3,3-diphenylpropyl) propylene diamine derivatives and their salts with therapeutically useful properties which are primarily useful in cardiac diseases as coronary blood flow enhancing and anti-rhythmic drugs. drugs.
Je žrtámo, že deriváty difenylpropylaminumají výhodné terapeutické vlastnosti (Arz-neimittel-Forschung 10, 569, 573, 583 (1960);Arch.Pharm. 295, 1196 (1962); J. Med. Che-mistry 7, 623 (1964). Soli těchto sloučeninjsou však ve vodě nesnadno rozpustné a pro-to se dají použít pro injekční účely pouzeomezeně. Dále je známo, že derivát hexobendiumethylendiaminu má rozšiřující účinek na ko-ronární cévy a derivát fenethaminhydrochlo-rid propylendiaminu má spasmolytický úči-nek.It is believed that the diphenylpropylaminate derivatives have advantageous therapeutic properties (Arz-neimittel-Forschung 10, 569, 573, 583 (1960); Arch.Pharm. 295, 1196 (1962); J. Med. Cheese 7, 623 (1964)). However, the salts of these compounds are not readily soluble in water and can be used for injection purposes only to a limited extent, and it is further known that the hexobendium ethylenediamine derivative has an enhancing effect on coronary vessels and the propylene diamine phenethamine hydrochloride derivative has a spasmolytic effect.
Bylo zjištěno, že nové deriváty propylendi-aminu s 3,3-difenylpr'opylovou skupinou o-becného vzorce IIt has been found that the novel propylenediamine derivatives with the 3,3-diphenylpropyl group of formula I
kde A a B znamenají atom vodíku nebo ace-tylovou skupinu, R a R1 znamenají na soběnezávisle methylovou, fenyloyou nebo ben-žjrřOýou Wn^ftiu nebo 'společně s atomemtíhifku, na nějž jsůu vázány tvoří cýkíohéxy-lovou skupinu a jejichž adiční soli s kyseli-riaWii mají rozšiřující účinek na kórohárnícévy a antirytmický účinek. Kromě toho ma-jí lokálně anestezující a ántiadrelínový ú-činék při nízíké toxicitě. Jejich zvlášť výhod-nou vlastností je snadná rozpustnost jejichSolí s anorganickými a organickými kyseli- 213322 213322 námi a jejich velmi dobrá resorpce. Dále bylo zjištěno, že' sloučeniny obecné-wherein A and B are hydrogen or acetyl, R and R 1 are independently methyl, phenyl or benzoyl, or together with the atom to which they are attached form a alkoxy group and the acid addition salts thereof; -riaWii have an expanding effect on coronary arteries and anti-rhythmic effects. In addition, it has a locally anesthetizing and anthiadrelin agent at low toxicity. Their particularly advantageous property is their ease of solubility with their inorganic and organic acids 213322 213322 and their very good resorption. Furthermore, it has been found that the
ho vzorce I a jejich soli lze získat podle vy-nálezu tím způsobem, že se difenylpropional-dehyd vzorce IIFormula I and salts thereof can be obtained according to the invention in such a way that the diphenylpropional dehydrochloride of Formula II is obtained
redukčně kondenzuje s diaminem obecnéhovzorce IIIreductively condenses with the diamine of formula III
R /R /
H--N—(CHžjs—N—CI-I I I \ A B Rl (ΙΠ), kde A znamená atom vodíku, B, R a R1 majíshora uvedený význam, v přítomnosti orga-nického rozpouštědla a takto získané slou-čeniny obecného vzorce I se popřípadě pře-vedou anorganickými nebo organickými ky-selinami na své soli.H - N— (CH 2 N-N-Cl-II) R 1 R (ΙΠ) wherein A is hydrogen, B, R and R 1 are as defined above, in the presence of an organic solvent and the compound of formula I is optionally converted to its salts by inorganic or organic acids.
Redukci lze provádět s výhodou katalytic-kou hydrogenací v přítomnosti obvyklýchkatalyzátorů kovu nebo katalyzátorů z uš-lechtilých kovů, jako například paládia, pla-tiny nebo niklu. Jako rozpouštědla se použí-vá například alkoholu nebo dioxanu. Reduk-ci lze. též provádět vodíkem ve stavu zrodu,například v přítomnosti amalgamu hliníku aalkoholu, amalganu sodíku, hydridoborita-nem sodným, hydridohlinitanem lithným aalkoholu. Redukci je možno provádět téželektrolyticky.The reduction can be carried out preferably by catalytic hydrogenation in the presence of customary metal catalysts or noble metal catalysts such as palladium, platinum or nickel. As the solvent, for example, an alcohol or dioxane is used. It can be reduced. It is also possible to carry out the process with hydrogen in the presence of, for example, aluminum amalgam and alcohol, sodium amalgan, sodium borohydride, lithium aluminum hydride and alcohol. The reduction can be performed electrolytically.
Jako sloučeniny obecného vzorce III lzepoužít s výhodou N-(l-fenyl-2-propyl )-1,3--propylerídiaminu nebo N-(l-fenyl-2-propyl)--N-acetylpropylen-l,3-diaminu.Preferred compounds of formula (III) are N- (1-phenyl-2-propyl) -1,3-propyleridamine or N- (1-phenyl-2-propyl) -N-acetylpropylene-1,3-diamine.
Ve sloučeninách obecného vzorce 1 se mo-hou skupiny A a/nebo B zaměnit. Přeměnulze uskutečnit známými postupy, tak napří-klad znamenají-li symboly A a/nebo B atomvodíku, mohou se tyto zaměnit za acylo-vouskupinu. Jako acylačního činidla se použijeanhydridu nebo halogenidu kyseliny a acy-lace se provede v přítomnosti činidla váza-jícího kyseliny, výhodně v přítomnosti ter-ciárního aminu, jako ťriethylaminu nebo py-ridinu. Při acylaci lze použít inertních orga-nických rozpouštědel, například benzenu, a-však jako acylační činidlo může sloužit irozpouštědlo, například anhydrid kyselinyoctové. Znamenají-li symboly A a/nebo Batom vodíku, může se atom vodíku alkylha-logenidy nebo aralkylhalogenidy, alkylsulfá-ty, aralkylsulfáty nebo podobnými sloučeni- nami přeměnit v alkylové nebo aralkylovéskupiny. Reakce se účelně provádějí v orga-nickém rozpouštědle v přítomnosti činidlavázajícího kyseliny (například uhličitanu al-kalického kovu, kyselého uhličitanu alkalic-kého kovu), avšak jako činidla vázajícíhokyseliny je možno použít i báze určené k al-kylaci. jako rozpouštědel lze výhodně použítalkoholů, acetonu nebo dimethylformamidu.Znamenají-li ve sloučeninách obecného vzor-ce I symboly A a/nebo B acylovou skupinu,lze je zahříváním s vodnou kyselinou k varunahradit atomem vodíku. Jako kyseliny ses výhodou používá kyseliny chlorovodíkové.Benzylovou skupinu lze obvyklým způsobemnahradit atomem vodíku.In the compounds of formula (1), groups A and / or B can be exchanged. The transformation is effected by known methods, for example, when A and / or B are hydrogen, they can be exchanged for acylo. The acylating agent used is an acid anhydride or acid halide and the acylation is carried out in the presence of an acid binding agent, preferably in the presence of a tertiary amine such as triethylamine or pyridine. In acylation, inert organic solvents such as benzene may be used, but a solvent such as acetic anhydride may serve as acylating agent. When A and / or Batom are hydrogen, the hydrogen atom can be converted into alkyl or aralkyl groups by alkyl halides or aralkyl halides, alkyl sulfates, aralkyl sulfates or the like. The reactions are conveniently carried out in an organic solvent in the presence of an acid scavenger (for example, an alkali metal carbonate, an alkali metal carbonate), but bases for alkylation can also be used as the acid scavenger. Alcohols, acetone or dimethylformamide may preferably be used as solvents. When A and / or B are acyl in the compounds of formula (I), they may be substituted by hydrogen for heating with aqueous acid. Hydrochloric acid is preferably used as the acid. The benzyl group can be conveniently substituted with a hydrogen atom.
Ze sloučenin obecného vzorce I lze zná-mým postupem získat reakcí s organickýminebo anorganickými kyselinami, například skyselinou chlorovodíkovou, sírovou, fosforeč-nou, vinnou, jantarovou, maleinovou, mléč-nou, citrónovou, nikotinovou nebo fumaro-vou příslušné soli.Salts of the compounds of the formula I can be obtained by reaction with organic or inorganic acids, for example hydrochloric, sulfuric, phosphoric, tartaric, succinic, maleic, lactic, citric, nicotinic or fumaric acids.
Sloučeniny obecného vzorce I a jejich solise mohou v terapii použít ve formě terapeu-tických přípravků, obsahujících účinnou lát-ku a inertní netoxické, terapeuticky vhod-né organické nebo anorganické nosiče. Pří-pravků lze použít ve formě dražé, entersol-ventních dražé, tablet pevných nebo s tenkýmpovlakem, pilulek, kapslí, kapalných suspen-zí, roztoků a emulzí. Jako nosičů se může po-užít mastku, škrobu, želatiny, vody a poly-etylenglykolů. Přípravky mohou popřípaděobsahovat i jiné pomocné látky jako napří-klad smáčedla, emulgační a suspendační či-nidla, soli a tlumivé látky podporující změ-nu osmotického tlaku, látky podporující roz-pad a/nebo další terapeuticky účinné látky.The compounds of formula (I) and their salts can be used in therapy in the form of therapeutic agents containing the active ingredient and inert, non-toxic, therapeutically useful organic or inorganic carriers. The compositions can be used in the form of dragees, entersoluble dragees, tablets of solid or thin coating, pills, capsules, liquid suspensions, solutions and emulsions. As carriers, talc, starch, gelatin, water and polyethylene glycols can be used. The compositions may optionally contain other excipients such as wetting agents, emulsifying and suspending agents, salts and osmotic pressure-altering promoters, dissolution enhancers and / or other therapeutically active agents.
Způsob podle vynálezu blíže objasňují ná-sledující příklady provedení. Příklad 1 10,5 g 3,3-difenylpropionaldehydu (připra-veného podle J. Med. Chem. 7, 623 (1964) a9,8 g N-(-fenyl-2-propyl)-l,3-propylendiaminu(připraveného podle německého patentu č.882 002) se rozpustí ve 100 ml ethanolu, za-hřívá 30 minut k varu, načež se hydrogenu-je za tlaku 1,1 MPa v přítomnosti paládia naaktivní uhlí jako katalyzátoru. Po ukončeníabsorpce vodíku se směs sfiltruje, rozpouš-tědlo oddestiluje a zbytek rozpustí v etheru.Působením ethanolového roztoku chlorovodí-ku se získá sůl, která se překrystaluje z etha-nolu. Tím se získá dihydrochlorid N-(3,3-di-f enylpropyl) -N‘- (l-fenyl-2-propyl) propylen-1,3-diaminu o teplotě tání 235 až 236 °C(sloučenina la).The invention is further illustrated by the following examples. Example 1 10.5 g of 3,3-diphenylpropionaldehyde (prepared according to J. Med. Chem. 7, 623 (1964) and 9.8 g of N - (- phenyl-2-propyl) -1,3-propylenediamine (prepared by according to German Patent No. 882,002) is dissolved in 100 ml of ethanol, heated to boiling for 30 minutes and then hydrogenated at a pressure of 1.1 MPa in the presence of palladium-on-charcoal catalyst. The residue is dissolved in ether and treated with ethanolic hydrochloric acid to give the salt which is recrystallized from ethanol to give N- (3,3-di-phenyl-propyl) -N'- (1- of phenyl-2-propyl) propylene-1,3-diamine, m.p. 235-236 ° C (compound Ia).
Dilatační účinek sloučeniny la, projevujícíse rozšířením koronárních cév in vitro nasrdci morčete podle Langendorffa je ve srov-nání s účinkem prenylaminu a papaverinuuveden v následující tabulce:The dilatation effect of compound 1a, manifested by coronary artery enlargement in vitro by Langendorff guinea pig lamb, is shown in the following table when compared to that of prenylamine and papaverine:
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CS787722A CS213322B2 (en) | 1972-04-24 | 1978-11-24 | Method of making the new derivatives of n-/3,3-diphenylpropyl/-propylendiamine |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HUCI1228A HU164883B (en) | 1972-04-24 | 1972-04-24 | |
CS732947A CS203057B2 (en) | 1972-04-24 | 1973-04-24 | Method of producing novel derivatives of n-/3,3-diphenyl propyl/-propylendiamine |
CS787722A CS213322B2 (en) | 1972-04-24 | 1978-11-24 | Method of making the new derivatives of n-/3,3-diphenylpropyl/-propylendiamine |
Publications (1)
Publication Number | Publication Date |
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CS213322B2 true CS213322B2 (en) | 1982-04-09 |
Family
ID=25745717
Family Applications (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CS766797A CS203059B2 (en) | 1972-04-24 | 1976-10-21 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/propylendiamine |
CS766796A CS203058B2 (en) | 1972-04-24 | 1976-10-21 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/-propylendiamine |
CS766798A CS203060B2 (en) | 1972-04-24 | 1976-10-21 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/propylendiamine |
CS787722A CS213322B2 (en) | 1972-04-24 | 1978-11-24 | Method of making the new derivatives of n-/3,3-diphenylpropyl/-propylendiamine |
CS791465A CS203061B2 (en) | 1972-04-24 | 1979-03-05 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/propylendiamine |
CS794290A CS203062B2 (en) | 1972-04-24 | 1979-06-21 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/-propylendiamine |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CS766797A CS203059B2 (en) | 1972-04-24 | 1976-10-21 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/propylendiamine |
CS766796A CS203058B2 (en) | 1972-04-24 | 1976-10-21 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/-propylendiamine |
CS766798A CS203060B2 (en) | 1972-04-24 | 1976-10-21 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/propylendiamine |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CS791465A CS203061B2 (en) | 1972-04-24 | 1979-03-05 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/propylendiamine |
CS794290A CS203062B2 (en) | 1972-04-24 | 1979-06-21 | Process for preparing new derivatives of n-/3,3-diphenylpropyl/-propylendiamine |
Country Status (1)
Country | Link |
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CS (6) | CS203059B2 (en) |
-
1976
- 1976-10-21 CS CS766797A patent/CS203059B2/en unknown
- 1976-10-21 CS CS766796A patent/CS203058B2/en unknown
- 1976-10-21 CS CS766798A patent/CS203060B2/en unknown
-
1978
- 1978-11-24 CS CS787722A patent/CS213322B2/en unknown
-
1979
- 1979-03-05 CS CS791465A patent/CS203061B2/en unknown
- 1979-06-21 CS CS794290A patent/CS203062B2/en unknown
Also Published As
Publication number | Publication date |
---|---|
CS203062B2 (en) | 1981-02-27 |
CS203061B2 (en) | 1981-02-27 |
CS203060B2 (en) | 1981-02-27 |
CS203059B2 (en) | 1981-02-27 |
CS203058B2 (en) | 1981-02-27 |
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