1. Field of the Invention
This invention relates to compositions of matter classified in the field of chemistry as 1-(substituted amino)-3-[4-R.sub.1 O-3-(lower-alkylthio, lower-alkylsulfinyl or lower-alkylsulfonyl)phenoxy]-2-propanols, to processes for the preparation thereof, to pharmaceutical compositions containing the same and to the method of use thereof in reducing blood pressure in mammals.
2. Description of the Prior Art
Among various known 1-(substituted amino)-3-substituted phenoxy)-2-propanols the compounds disclosed in the following patents and publications are believed to constitute the most pertinent prior art relative to the present invention.
L. Villa et al., Il Farmaco, Ed. Sci., 24, 349-357 (1969) disclose 1-(isopropylamino)-3-[2-(methylthio)phenoxy]-2-propanol which was prepared in connection with a study of structure-activity relationships among a group of beta-adrenolytics.
Keizer et al., U.S. Pat. No. 3,542,874, patented Nov. 4, 1970 disclose compounds of the formula: ##STR1## wherein: R.sub.1 is alkyl of 1 to 4 carbon atoms inclusive, and
R.sub.2 is a member selected from the group consisting of alkyl of 1 to 12 carbon atoms inclusive, alkenyl of 2 to 12 carbon atoms inclusive, alkinyl of 2 to 12 carbon atoms inclusive, cycloalkyl of 3 to 12 carbon atoms inclusive and aralkyl of 7 to 12 carbon atoms inclusive. Specific compounds disclosed include those wherein R.sub.1 is methyl or ethyl and R.sub.2 is isopropyl; R.sub.1 is methyl, ethyl or propyl and R.sub.2 is tertiary butyl; R.sub.1 is methyl or propyl and R.sub.2 is 1-methyl-3-phenylpropyl. The compounds are stated to exhibit .beta.-sympatholitical activity. PA1 R.sub.2 represents hydrogen, lower-alkyl or lower-alkylsulfonyl; PA1 R.sub.3 represents hydrogen or lower-alkyl and PA1 R.sub.4 represents hydrogen or lower-alkylsulfonyl, only one of R.sub.2 and R.sub.4 being lower-alkylsulfonyl. Specific compounds disclosed include those wherein R.sub.1 is isopropyl or t-butyl, R.sub.2 is hydrogen, R.sub.3 is hydrogen or methyl and R.sub.4 is methylsulfonyl; R.sub.1 is isopropyl, R.sub.2 is methylsulfonyl, R.sub.3 and R.sub.4 are each hydrogen; R.sub.1 is 4-methoxy(or 4-hydroxy)-.alpha.,.alpha.-dimethylphenethyl, R.sub.2 is hydrogen, R.sub.3 is methyl and R.sub.4 is methylsulfonyl. The compounds are stated to possess anti-arrhythmic and/or cardio-selective .beta.-adrenergic blocking properties and to be useful in the treatment of hypertension. PA1 R.sub.1 is 1-8C alkyl and PA1 R.sub.2 is 6-12C alkyl or (5-8C)cycloalkyl-(2-6C)alkyl including the species wherein A, B and R are hydrogen, R.sub.2 is octyl and R.sub.1 S is 3-isopropylthio. The compounds are stated to increase peripheral blood flow, relax vascular smooth muscle and inhibit thromboctye aggregation, but to be practically free of .beta.-adrenergic blocking activity. PA1 R.sub.1 is hydrogen, lower-alkyl or benzyl; PA1 R.sub.2 is lower-alkyl or ##STR6## in which: R.sub.3 and R.sub.4 are independently hydrogen or lower-alky; PA1 Q is hydrogen, lower-alkyl, hydroxy or lower-alkoxy; PA1 n is 1, 2 or 3; and PA1 acid-addition salts thereof.
M. L. Hoefle, et al., J. Med. Chem., 18, 148-152 (1975) disclose in most pertinent part the compound of the following formula which is stated to have .beta.-adrenergic blocking activity: ##STR2##
Comer et al., U.S. Pat. No. 4,067,904, patented Jan. 10, 1978 disclose a group of compounds having the formula: ##STR3## wherein R.sub.1 represents a branched-chain alkyl radical of 3 or 4 carbon atoms such as isopropyl, sec-butyl, isobutyl and t-butyl, phenoxyisopropyl, 4-hydroxy-.alpha.,.alpha.-dimethylphenethyl, 4-methoxy-.alpha.,.alpha.-dimethylphenethyl or cycloalkyl of 3 to 6 carbon atoms inclusive;
Belgian Pat. No. 871,143, published Apr. 10, 1979 and equivalent United Kingdom Patent Application No. 2,006,197A, published May 2, 1979, disclose a group of compounds having the formula ##STR4## wherein A, B and R are hydrogen or 1-4C alkyl;
USPTO Backgrounds
USPTO Backgrounds