Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1985-06-12
1994-05-10
Brown, Johnnie R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 45, 536 2722, A61K 3170, C07H 19167
Patent
active
053107314
ABSTRACT:
Compounds of the formula ##STR1## are disclosed, wherein R.sub.1, represents secondary alkyl; aralkyl; cycloalkyl; heteroaryl substituted alkyl; norbornyl; and substituted secondary alkyl, aralkyl, cycloalkyl, heteroaryl substituted alkyl, norbornyl; and para-substituted phenyl groups; and R.sub.2 and R.sub.3 are hydrogen or pharmacologically acceptable acyl groups. The compounds of the invention are useful as cardiovascular vasodilator or anti-hypertensive agents. The therapeutically useful compounds of the invention as well as similar 5'-N and N-6 substituted adenosine 5'-uronamides are prepared, in accordance with a novel process, from isopropylidene (or otherwise suitably blocked) inosine-5' -uronic acid. Isopropylideneinosine-5' -uronic acid is reacted with a suitable inorganic acid halide, such as thionyl chloride, to yield 6-halogeno-9-[ 2',3' -O-isopropylidene-.beta.-D-ribofuranosyl-5-uronic acid halide] -9H-purine. This intermediate is reacted with an amine of the general formula R.sub.4,R.sub.5 NH to give a 6-halogeno substituted, substituted uronic acid amide of the formula ##STR2## wherein X is halogen. Reaction of the latter intermediate with an amine of the formula R.sub.1 --NH.sub.2, and removal of the isopropylidene (or other) blocking groups yields the compounds of the invention.
REFERENCES:
patent: 3502649 (1970-03-01), Thiel
patent: 3509129 (1970-04-01), Kampe et al.
patent: 3590029 (1971-06-01), Koch et al.
patent: 3851056 (1974-11-01), Stork et al.
patent: 3901876 (1975-08-01), Vorbrug et al.
patent: 3931401 (1976-01-01), Prasad et al.
patent: 3966916 (1976-06-01), Kampe et al.
patent: 4029884 (1977-06-01), Stein et al.
patent: 4090021 (1978-05-01), Vorgrug et al.
patent: 4167565 (1979-09-01), Stein et al.
patent: 4224438 (1980-09-01), Fauland et al.
patent: 4514405 (1985-04-01), Irmscher et al.
Goodman, "Chemical Syntheses and Transformations of Nucleosides" in Basic Principles in Nucleic Acid Chemistry, P. O. P. Ts'O ed., Academic Press, New York, 1974, see pp. 150-151.
Schmidt and Fritz, Chem Ber 103, 1867-1871 (1970).
Fox and Kurpis, The Journal of Biological Chemistry, vol. 258, No. 11, Issue of Jun. 10, pp. 6952-6955 (1983).
Schuske, U., In Berne et al, Ch 6 of "Regulatory Function of Adenosine" (London) (Pub) pp. 77-96, 1983, Martinus Nishoff.
Stein et al, N.Y. Acad. Sci, 255, 380-389, 1975.
Daly, J. Med. Chem., 25(3), pp. 197-207, 1982.
Stein, J. Med. Chem., 16(11), pp. 1306-1309, 1973.
J. W. Daly, et al., "Structure-Activity Relationships for N.sup.6 -Substituted Adenosine at a Brain A.sub.1 -Adenosine Receptor with a Comparison to an A.sub.2 -Adenosine Receptor Regulating Coronary Blood Flow," Biochemical Pharmacology, vol. 35, No. 15, pp. 2467-2481, 1986.
Chemical Abstract 72:3706.
R. A. Olsson, et al., "Use of Structure-Activity Relationship in the Study of Adenosine Receptors," Methods of Pharm. vol. 6, 1985.
Olsson Ray A.
Thompson Robert D.
Baran Robert J.
Brown Johnnie R.
Crane L. Eric
Hackler Walter A.
Whitby Research, Inc.
LandOfFree
N-6 substituted-5'-(N-substitutedcarboxamido)adenosines as cardi does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with N-6 substituted-5'-(N-substitutedcarboxamido)adenosines as cardi, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and N-6 substituted-5'-(N-substitutedcarboxamido)adenosines as cardi will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2412367