Tropolone derivatives and pharmaceutical composition thereof for preventing and treating ischemic diseases

A compound of the formula:

• ##STR46## wherein R.sub.10 is a moiety of the formula II ##STR47## wherein R.sub.1 and R.sub.2 are the same or different and are:
• (a) hydrogen,
• (b) C.sub.1 -C.sub.5 alkyl,
• (c) aryl,
• (d) 2-pyridyl, 3-pyridyl, or 4-pyridyl, or
• (e) p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, o,m-dichlorophenyl, p-fluorophenyl, p-nitrophenyl, m-nitrophenyl, o-nitrophenyl, p-cyanophenyl, m-cyanophenyl, o-cyanophenyl, p-methoxyphenyl, m-methoxyphenyl, o-methoxyphenyl, m,p-dimethoxyphenyl;
• wherein R.sub.41 is
• (a) --OR.sub.3,
• (b) --OR.sub.6,
• (c) --NR.sub.7 R.sub.8,
• (d) --N(R.sub.51)--(CH.sub.2).sub.m --R.sub.61, or
• (e) a group represented by the formula IV ##STR48## wherein R.sub.3 is (a) hydrogen,
• (b) C.sub.1 -C.sub.5 alkyl,
• (c) C.sub.1 -C.sub.5 alkyl substituted by --OH, --COOR.sub.5, or --CN.
• (d) C.sub.7 -C.sub.20 aralkyl,
• (e) halogen;
• wherein R.sub.5 is
• (a) hydrogen, or
• (b) C.sub.1 -C.sub.5 alkyl;
• wherein R.sub.6 is
• (a) hydrogen,
• (b) C.sub.1 -C.sub.5 alkyl,
• (c) C.sub.1 -C.sub.5 alkyl substituted by OH, COOR.sub.5 or CN, or
• (d) C.sub.7 -C.sub.20 aralkyl;
• wherein R.sub.7 and R.sub.8 are the same or different and are:
• (a) hydrogen,
• (b) C.sub.1 -C.sub.5 alkyl,
• (c) C.sub.1 -C.sub.5 alkyl substituted by --OH, --COOR.sub.5, or --CN, or
• (d) C.sub.7 -C.sub.20 aralkyl;
• wherein R.sub.11 is
• (a) hydrogen,
• (b) C.sub.1 -C.sub.3 alkyl,
• (c) aryl,
• (d) 2-pyridyl, 3-pyridyl, or 4-pyridyl, or
• (e) a substituted aryl selected from p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, o,m-dichlorophenyl, p-fluorophenyl, p-trifluorophenyl, p-nitrophenyl, m-nitrophenyl, o-nitrophenyl, p-cyanophenyl, m-cyanophenyl, o-cyanophenyl, p-methoxyphenyl, m-methoxyphenyl, o-methoxyphenyl, m,p-dimethoxyphenyl;
• wherein R.sub.21 and R.sub.31 are the same or different and are
• (a) hydrogen, or
• (b) C.sub.1 -C.sub.3 alkyl;
• wherein R.sub.61 is
• (a) aryl,
• (b) 2-pyridyl, 3-pyridyl, or 4-pyridyl,
• (c) --OR.sub.71,
• (d) --CO.sub.2 R.sub.81,
• (e) --NR.sub.91 R.sub.101, or
• (f) a substituted aryl selected from p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, o,m-dichlorophenyl, p-fluorophenyl, p-trifluorophenyl, p-nitrophenyl, m-nitrophenyl, o-nitrophenyl, p-cyanophenyl, m-cyanophenyl, o-cyanophenyl, p-methoxyphenyl, m-methoxyphenyl, o-methoxyphenyl, m,p-dimethoxyphenyl;
• wherein R.sub.51, R.sub.71, and R.sub.81 are the same or different and are
• (a) hydrogen, or
• (b) C.sub.1 -C.sub.3 alkyl;
• wherein R.sub.91 and R.sub.101 are the same or different and are
• (a) hydrogen,
• (b) C.sub.1 -C.sub.3 alkyl,
• (c) aryl group,
• (d) 2-pyridyl, 3-pyridyl, or 4-pyridyl, or
• (e) a substituted aryl selected from p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, o,m-dichlorophenyl, p-fluorophenyl, p-trifluorophenyl, p-nitrophenyl, m-nitrophenyl, o-nitrophenyl, p-cyanophenyl, m-cyanophenyl, o-cyanophenyl, p-methoxyphenyl, m-methoxyphenyl, o-methoxyphenyl, m,p-dimethoxyphenyl;
• wherein Ar.sub.1 and Ar.sub.2 are the same or different aryl group optionally substituted by
• (a) halogen,
• (b) trihalomethyl,
• (c) C.sub.6 -C.sub.10 aryl, or
• (d) C.sub.6 -C.sub.10 aryl substituted by C.sub.1 -C.sub.3 alkoxy;
• wherein X is
• (a) --O--,
• (b) --CH.sub.2 --, or
• (c) --N--(CH.sub.2).sub.p --R.sub.11 ;
• wherein m is 1, 2, 3, or 4;
• wherein n is 0, 1, or 2;
• wherein p is 0, 1, or 2;
• and
• wherein q is 1 or 2;
• or a pharmaceutically acceptable ester selected from those with acetic acid, propionic acid, and oxalic acid, or a pharmaceutically acceptable salt thereof.