4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid analogs having antihypertensive activity

A compound having the formula (I) ##STR54## and their pharmaceutically acceptable base or acid addition salts;

• wherein (1) --- is a single or a double bond;
• (2) one of R.sub.1 is present and is
• (a) alkyl of from four to twenty carbons, inclusive,
• (b) ##STR55## wherein y is zero, one, two, three, four or five, R' is cycloalkyl of from four to twenty carbons, inclusive in a one, two or three saturated ring system, said ring consisting of from four to eight carbons inclusive, each ring unsubstituted or substituted by a straight or branched lower alkyl group, naphthyl, heteroaryl consisting of 2-, 3-, or 4-pyridyl;
• 1-, 2-, or 4-imidazolyl;
• 1-, 2-, 3-, 4-, 5-, 6-, or 7-indolyl;
• 2-, or 3-thienyl;
• 2-, or 3-furyl;
• or 1-, 2-, or 3-pyrazolyl, phenyl unsubstituted or substituted with of from one through five substituents selected from the group consisting of lower alkyl, halo, trifluoromethyl, hydroxy, lower alkoxy, lower alkyl acyloxy, amino, N-lower monoalkylamino, N,N-lower dialkylamino, lower thioalkyl, lower alkylsulfonyl, nitro and ##STR56## wherein R.sub.10 is lower alkyl, phenyl unsubstituted or substituted by lower alkyl, or --NHR.sub.11 wherein R.sub.11 is hydrogen or lower alkyl, and R" is hydrogen, lower alkyl, cycloalkyl of from four to twenty carbons, inclusive in a one two or three saturated ring system, said ring consisting of from four to eight carbons inclusive, each ring unsubstituted or substituted by a straight or branched lower alkyl group, naphthyl, phenyl unsubstituted or substituted with of from one through five substituents selected from the group consisting of alkyl, halo, trifluoromethyl, amino, N-lower monoalkylamino, N,N-lower dialkylamino, lower thioalkyl, lower alkylsulfonyl, and nitro;
• (3) R.sub.2 is
• (a) hydrogen,
• (b) halo,
• (c) lower alkyl,
• (d) R'--(CH.sub.2)--.sub.x wherein x is one, two, three, four, or five and R' is independently as defined above,
• (e) ##STR57## wherein R' is independently as defined above, or (f) R'--CH(OH)-- wherein R' is independently as defined above;
• (4) R.sub.3 is
• (a) R'--CH).sub.x wherein x and R' are independently as defined above,
• (b) ##STR58## wherein R' and y are independendently as defined above, and R'" is lower alkyl, cycloalkyl, of from four to twenty carbons, inclusive in a one, two or three saturated ring system, said ring consisting of from four to eight carbons inclusive, each ring unsubstituted or substituted by a straight or branched lower alkyl group, naphthyl, phenyl unsubstituted or substituted with of from one to five substituents selected from the group consisting of alkyl, halo, trifluoromethyl, amino, N-lower monoalkylamino, N,N-lower dialkylamino, lower thioalkyl, lower alkylsulfonyl, and nitro;
• ##STR59## wherein R.sub.5 is (i) alkyl of from one to fifteen carbons, inclusive,
• (ii) ##STR60## wherein R', R", and y are independently as defined above, (iv) --CH.dbd.CR.sub.6 --R.sub.1 wherein R.sub.6 is hydrogen or lower alkyl and R.sub.1 is as defined above,
• (v) ##STR61## wherein y, R' and R.sub.6 are independently as defined above, (vi) R'--CH.sub.2 --.sub.y --O-- wherein y and R' are independently as defined above,
• (vii) ##STR62## wherein R', R", and y are independently as defined above, (d) ##STR63## wherein R.sub.5 is independently as defined above;
• (5) R.sub.4 is
• (a) --CH.sub.2 OR.sub.7 wherein R.sub.7 is hydrogen, lower acyl, a lower alkyl,
• (b) ##STR64## wherein R.sub.7 is independently as defined above and R.sub.8 is hydrogen, lower alkyl, or benzyl,
• (c) ##STR65## (d) --C.tbd.N, (e) ##STR66## wherein R.sub.9 is hydrogen, lower alkyl, or benzyl;
• and (6) n is one;
• with the overall proviso that R.sub.9 cannot be hydrogen, methyl or ethyl when R.sub.3 is R'--(CH.sub.2)--.sub.x or ##STR67## wherein R.sub.5 is R'--(CH.sub.2).sub.y O-- or ##STR68## wherein each of R', R", x, and y are as defined above.