Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-07-29
1996-07-30
Gupta, Yogendra N.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514242, 514245, 514269, 514275, 514385, 514397, 540553, 544182, 544212, 544330, 544332, 5483311, 5483315, 5483351, A61K 3133, A61K 31505, C07D24304, C07D23942
Patent
active
055411800
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is based upon PCT Application Serial No. PCT/EP 93/00435, filed Feb. 19, 1993, which claims priority from U.S. patent application Ser. No. 842,560, filed Feb. 27, 1992.
BACKGROUND OF THE INVENTION
In EP-0,387,771 there are described benzopyran derivatives which show an inhibitory activity on Maillard reaction and possess an antioxidizing effect. In Arzneim.-Forsch. 25 (9), p. 1404 ( 1975) there is described [2-[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]amino]ethylguanidine in a study concerning noradrenaline depletion effects. In WO-83/03607 a number of cyanoguanidines are described having anti-hypertensive and vasodilator activity. Our novel compounds differ in that they have selective vasoconstrictor activity.
DESCRIPTION OF THE INVENTION
The present invention is concerned with [(benzodioxan, benzofuran or benzopyran)alkylamino]alkyl substituted guanidines having the formula ##STR3## the pharmaceutically acceptable acid addition salts thereof, and the stereochemically isomeric forms thereof, wherein
X is O, CH.sub.2 or a direct bond;
R.sup.1 is hydrogen or C.sub.1-6 alkyl;
R.sup.2 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 alkenyl or C.sub.3-6 alkynyl;
R.sup.3 is hydrogen or C.sub.1-6 alkyl; or
R.sup.2 and R.sup.3 taken together form a bivalent radical of formula --(CH.sub.2).sub.m -- wherein m is 4 or 5; or
R.sup.1 and R.sup.2 taken together form a bivalent radical of formula --CH.dbd.CH-- or of formula --(CH.sub.2).sub.n --, wherein n is 2, 3 or 4; or
R.sup.3 may represent a bond when R.sup.1 and R.sup.2 taken together form a bivalent radical of formula --CH.dbd.CH--CH.dbd., --CH.dbd.CH--N.dbd., or --CH.dbd.N--CH.dbd., wherein one or two hydrogen atoms can be replaced by halo, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, cyano, amino, mono- or di(C.sub.1-6 alkyl)amino, mono- or di(C.sub.3-6 cycloalkyl)amino, aminocarbonyl, C.sub.1-6 alkyloxycarbonylamino, C.sub.1-6 alkylaminocarbonylamino;
R.sup.4 is hydrogen or C.sub.1-6 alkyl;
Alk.sup.1 is a bivalent C.sub.1-3 alkanediyl radical;
A is a bivalent radical of formula: ##STR4## wherein each R.sup.5 is hydrogen or C.sub.1-4 alkyl; wherein each R.sup.6 is hydrogen or C.sub.1-4 alkyl; is 0, 1 or 2; and C.sub.3-6 alkenyl, C.sub.3-6 alkynyl, hydroxy, C.sub.1-6 alkyloxy, cyano, aminoC.sub.1-6 alkyl, carboxyl, C.sub.1-6 alkyloxycarbonyl, nitro, amino, aminocarbonyl, C.sub.1-6 alkylcarbonylamino, or mono- or di(C.sub.1-6 alkyl)amino; guanidine is excluded.
The compounds of formula (I) wherein R.sup.2, R.sup.3 or R.sup.6 are hydrogen may also exist in their tautomeric forms. Such forms although not explicitly indicated in the above formula are intended to be included within the scope of the present invention.
As used in the foregoing definitions halo defines fluoro, chloro, bromo and iodo; C.sub.1-4 alkyl defines straight and branch chained saturated hydrocarbon radicals having 1 to carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylethyl, 2-methylpropyl and the like; C.sub.1-6 alkyl defines C.sub.1-4 alkyl and the higher homologues thereof having 5 to 6 carbon atoms such as, for example, pentyl, hexyl, 1-methylbutyl and the like; C.sub.3-6 alkenyl defines straight and branch chained hydrocarbon radicals containing one double bond and having from 3 to 6 carbon atoms, such as, for example, 2-propenyl, 3-butenyl, 2-butenyl, 2-pentenyl, 3-pentenyl, 3-methyl-2-butenyl and the like; and the carbon atom of said C.sub.3-6 alkenyl being connected to a nitrogen atom preferably is saturated, C.sub.3-6 alkynyl defines straight and branch chained hydrocarbon radicals containing one triple bond and having from 3 to 6 carbon atoms, such as, for example, 2-propynyl, 3-butynyl, 2-butynyl, 2-pentynyl, 3-pentynyl, 3-hexynyl, and the like; and the carbon atom of said C.sub.3-6 alkynylradical being connected to a nitrogen atom preferably is saturated; C.sub.3-6 cycloalkyl is generic to cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; C.sub.1-3 alkanediyl defines bivalent straight and branch chained saturat
REFERENCES:
patent: 3166561 (1965-01-01), Janssen et al.
patent: 3944549 (1976-03-01), Lafon
patent: 4405622 (1983-09-01), Kluge
Benkert et al., "Beziehungen zwischen struktur und Noradrenalin-entspeichernder Wirkung von Guanidin-und Amidinderivaten", Arzneim.-Forsch. (Drug Res.) 25, Nr. 9 (1975), 1404-1408.
Manoury et al., "Synthesis and Antihypertensive Activity of a Series of 4-Amino-6,7-dimethoxyquinazoline Derivatives", J. Med. Chem., 1986, 19-25.
De Bruyn Marcel F. L.
Janssens Walter J. J.
Van Lommen Guy R. E.
Gupta Yogendra N.
Janssen Pharmaceutica N.V.
Metz Charles J.
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