Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1988-01-05
1990-05-15
Raymond, Richard L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
544245, 544246, 546 90, 546146, 546148, C07D21704
Patent
active
049259431
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns new 2-(2-aminobenzyl or 2-nitrobenzyl)-1,2,3,4-tetrahydroisoquinoline derivatives, as well as their salts, processes for their preparation, their pharmacological .alpha.2-adrenergic blocking activity, and pharmaceutical compositions containing same.
At present, numerous .alpha.-adrenolytic molecules have been discovered. However, few among them have a good .alpha.2-adrenergic selectivity. For example, yohimbine, currently used as an .alpha.2 blocking reference substance, although having only slight affinity for .alpha.1 receptors, has other effects which limit its therapeutic use.
The present invention is thus directed toward effecting specific .alpha.2 blocking molecules. The results of this work have permitted, by modifying 2-benzylisoquinoline (having a chemical structure different than that of yohimbine), selecting new compounds with .alpha.2 adrenergic affinity.
The substances according to the invention also have the advantage of being more water-soluble, more stable and less expensive to make than yohimbine.
The invention has for an object 2-(2-aminobenzyl or 2-nitrobenzyl)-1,2,3,4-tetrahydroisoquinoline derivatives, as well as their mineral or organic acid addition salts, corresponding to the general formula I: ##STR2## in which each of substituents R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 or R.sub.8 may represent either a hydrogen atom, a straight or branched chain alkyl group preferably having 1 to 4 carbon atoms, a straight or branched chain alkoxy group preferably having 1 to 4 carbon atoms, a hydroxy group or corresponding esters, a phenoxy group, a benzyloxy group, a methylenedioxy (--O--CH.sub.2 --O--) bridge when this substituent is connected with an adjacent carbon, a halogen, a nitro group, or an amine function corresponding to primary, secondary or tertiary amino, or quaternary ammonium;
each of substituents R.sub.9 or R.sub.10 may represent either a hydrogen atom, a straight or branched chain alkyl group preferably having 1 to 4 carbon atoms, an arylalkyl group, an amine function corresponding to primary, secondary or tertiary amino or quaternary ammonium, or may both be an oxygen atom; each of substituents R.sub.11 or R.sub.12 may represent either a hydrogen atom, or a straight or branched chain alkyl group preferably having 1 to 4 carbon atoms;
R.sub.11 and R.sub.12 may also together form an oxygen atom;
R.sub.13 may represent either a hydrogen atom, or a straight or branched chain alkyl group preferably having 1 to 4 carbon atoms;
with the exclusion of the compound where R.sub.1 =R.sub.4 =R.sub.5 =R.sub.7 =R.sub.8 =R.sub.9 =R.sub.10 =R.sub.11 =R.sub.12 =R.sub.13 =H, R.sub.2 =R.sub.3 =OCH.sub.3 and R.sub.6 =CH.sub.3.
In the general formula I and hereinafter, the term alkyl radical preferably containing 1 to 4 carbon atoms designates, for example, a methyl radical and the term alkoxy radical represents, for example, methoxy. The halogen atom may be either fluorine, chlorine, bromine or iodine.
The substituents on tetrahydroisoquinoline may be at any position on the benzenic nucleus, but preferably at position 6 and 7 or 6 or 7, which corresponds to R.sub.3 and R.sub.2.
The substituents on the 2-aminobenzyl or 2-nitrobenzyl group may be at any position on the benzene nucleus, but preferably at the para and meta or para or meta positions, which correspond to R.sub.6 and R.sub.7.
The mineral or organic acid addition salts may for example be salts formed with hydrochloric acid.
Among the products according to the invention, there can be mentioned the derivatives corresponding to formula I above, as well as their addition salts with mineral or organic salts, characterized in that, in the said formula I, each of the substituents R.sub.9 or R.sub.10 may represent either a hydrogen atom, or a methyl group, or may each be an oxygen atom; each of the substituents R.sub.2 or R.sub.3 may represent a hydrogen atom, or a methoxy group, or a benzyloxy group; each of substituents R.sub.6 or R.sub.7 may represent either a hydrogen atom, or a methoxy gr
REFERENCES:
patent: 3542782 (1970-11-01), Houlihan et al.
Pictet et al., "Chem. Ber.", vol. 44, 1911, pp. 2036-2045.
Spath et al., "Chem. Ber.", vol. 72, 1939, pp. 334-338.
Heitz Christiane
Jung Louis
Kanmacher Isabelle
Schott Christa
Stambach Jean-Francois
Raymond Richard L.
Turnipseed James H.
LandOfFree
2-(2-aminobenzyl or 2-nitrobenzyl)-1,2,3,4-tetrahydroisoquinolin does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 2-(2-aminobenzyl or 2-nitrobenzyl)-1,2,3,4-tetrahydroisoquinolin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 2-(2-aminobenzyl or 2-nitrobenzyl)-1,2,3,4-tetrahydroisoquinolin will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-622300