Styryl pyrazoles, isoxazoles and analogs thereof having activity as 5-lipoxygenase inhibitors, pharmaceutical compositions and methods of use therefor

A compound of the formula (I) ##STR38## or pharmaceutically acceptable salt thereof;

• wherein (1) -- is a single or double bond;
• (2) R, R.sub.1, and R.sub.2 may be the same or different and are selected from the group consisting of hydrogen, lower alkyl, hydroxy, OR.sub.3 wherein R.sub.3 is lower alkyl, C(O)R.sub.4 wherein R.sub.4 is hydrogen or lower alkyl, OC(O)R.sub.3 wherein R.sub.3 is independently as defined above, C(O)R.sub.3 wherein R.sub.3 is independently as defined above, C(O)R.sub.3 wherein R.sub.3 is independently as defined above, NR.sub.6 R.sub.7 wherein R.sub.6 and R.sub.7 may be the same or different and are hydrogen or lower alkyl, NHC(O)R.sub.3 wherein R.sub.3 is independently as defined above, NHCHO, NHSO.sub.2 R.sub.3 wherein R.sub.3 is independently as defined above, NHCONHR.sub.4 wherein R.sub.4 is as defined above, hydroxymethyl, halogen, trifluoromethyl, SR.sub.4 wherein R.sub.4 is independently as defined above, or nitro;
• (3) Q is CH.dbd.CH;
• (4) X and Y are one of the following combinations:
• ______________________________________ X Y ______________________________________ N O or S O N S N ______________________________________
• (5) Z is H, lower alkyl, aryl, aralkyl, OC(O)R.sub.3 wherein R.sub.3 is independently as defined above, C(O)R.sub.4 wherein R.sub.4 is independently as defined above, C(O)OR.sub.3 wherein R.sub.3 is independently as defined above, (CH.sub.2).sub.1-2 OH, CH(R'.sub.1)CO.sub.2 R'.sub.2 wherein R'.sub.1 and R'.sub.2 may be the same or different and are hydrogen or lower alkyl, halogen, trifluoromethyl, ##STR39## wherein R, R.sub.1 and R.sub.2 are independently as defined above;
• excluding a compound of the formula ##STR40## wherein one of R, R.sub.1 and R.sub.2 is 2-hydroxy and Z is hydrogen or alkyl.

A compound of the formula (I) ##STR41## or pharmaceutically acceptable salt thereof;

• wherein (1) -- is a single or double bond;
• (2) R, R.sub.1, and R.sub.2 may be the same or different and are selected from the group consisting of hydrogen, lower alkyl, hydroxy, OR.sub.3 wherein R.sub.3 is lower alkyl, C(O)OR.sub.4 wherein R.sub.4 is hydrogen or lower alkyl, OC(O)R.sub.3 wherein R.sub.3 is independently as defined above, C(O)R.sub.3 wherein R.sub.3 is independently as defined above, NR.sub.6 R.sub.7 wherein R.sub.6 and R.sub.7 may be the same or different and are hydrogen or lower alkyl, NHC(O)R.sub.3 wherein R.sub.3 is independently as defined above, NHCHO, NHSO.sub.2 R.sub.3 wherein R.sub.3 is independently as defined above, NHCONHR.sub.4 where R.sub.4 is as defined above, hydroxymethyl, halogen, trifluoromethyl, SR.sub.4 wherein R.sub.4 is independently as defined above, or nitro;
• (3) Q is CH.dbd.CH;
• (4) X and Y are one of the following combinations:
• ______________________________________ X Y ______________________________________ N NR.sub.5, O or S NR.sub.5 N O N S N ______________________________________
• wherein R.sub.5 is ##STR42## wherein R'.sub.1 and R'.sub.2 may be the same or different and are hydrogen or lower alkyl, C(O)R.sub.4 wherein R.sub.4 is independently as defined above, cycloalkyl of from three to twenty carbons having of from three to eight ring carbons optionally substituted by alkyl of from one to twelve carbons, or aralkyl;
• (5) Z is H, lower alkyl, aryl, aralkyl, OC(O)R.sub.3 wherein R.sub.3 is independently as defined above, C(O)R.sub.4 wherein R.sub.4 is independently as defined above, C(O)OR.sub.3 wherein R.sub.3 is independently as defined above, (CH.sub.2).sub.1-2 OH, CH(R'.sub.1)CO.sub.2 R'.sub.2 wherein R'.sub.1 and R'.sub.2 are independently as defined above, halogen, trifluoromethyl, ##STR43## wherein R, R.sub.1 and R.sub.2 are independently as defined above;
• excluding a compound of the formula ##STR44## wherein one of R, R.sub.1 and R.sub.2 is 2-hydroxy and Z is hydrogen or alkyl.

A compound of the formula (I) ##STR45## R, R.sub.1, and R.sub.2 may be the same or different and are selected from the group consisting of hydrogen, lower alkyl, hydroxy, OR.sub.3 wherein R.sub.3 is lower alkyl, C(O)OR.sub.4 wherein R.sub.4 is hydrogen or lower alkyl, OC(O)R.sub.3 wherein R.sub.3 is independently as defined above, C(O)R.sub.3 wherein R.sub.3 is independently as defined above, NR.sub.6 R.sub.7 wherein R.sub.6 and R.sub.7 may be the same or different and are hydrogen or lower alkyl, NHC(O)R.sub.3 wherein R.sub.3 is independently as defined above, NHCHO, NHSO.sub.2 R.sub.3 wherein R.sub.3 is independently as defined above, NHCONHR.sub.4 where R.sub.4 is as defined above, hydroxymethyl, halogen, trifluoromethyl, SR.sub.4 wherein R.sub.4 is independently as defined above, or nitro;

• (3) Q is ##STR46## wherein R.sub.4 is independently as defined above;
• (4) X and Y are one of the following combinations:
• ______________________________________ X Y ______________________________________ N NR.sub.5, O or S NR.sub.5 N O N S N ______________________________________
• wherein R.sub.5 is hydrogen, lower alkyl, ##STR47## wherein R'.sub.1 and R'.sub.2 may be the same or different and are hydrogen or lower alkyl, C(O)R.sub.4 wherein R.sub.4 is independently as defined above, cycloalkyl of from three to twenty carbons having of from three to eight ring carbons optionally substituted by alkyl of from one to twelve carbons, aryl, or aralkyl;
• (5) Z is H, lower alkyl, aryl, aralkyl, OC(O)R.sub.3 wherein R.sub.3 is independently as defined above, C(O)R.sub.4 wherein R.sub.4 is independently as defined above, C(O)OR.sub.3 wherein R.sub.3 is independently as defined above, (CH.sub.2).sub.1-2 OH, CH(R'.sub.1)CO.sub.2 R'.sub.2 wherein R'.sub.1 and R'.sub.2 are independently as defined above, halogen, trifluoromethyl, ##STR48## wherein R, R.sub.1 and R.sub.2 are independently as defined above.