Patent ID: 6214855
Filing Date: 2001-04-10
Classification: A61K

Abstract:
A method of treatment of a mammal currently afflicted with a stroke or previously afflicted with a stroke, said method comprising administering to said mammal a therapeutically effective amount of an N-heterocyclic glyoxylamide compound represented by the formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof: ##STR25##wherein;E and F are differently C or N;----- is presence or absence of a double bond;each X is independently oxygen or sulfur;R.sub.11 is selected from groups (a), (b) and (c) where;(a) is C.sub.7 -C.sub.20 alkyl, C.sub.7 -C.sub.20 alkenyl, C.sub.7 -C.sub.20 alkynyl; or carbocyclic radical selected from the group cycloalkyl, cycloalkenyl, phenyl, naphthyl, norbornanyl, bicycloheptadienyl, tolyl, xylyl, indenyl, stilbenyl, terphenylyl, diphenylethylenyl, phenyl-cyclohexenyl, acenaphthyl, and anthryl, biphenylyl, bibenzylyl and related bibenzylyl homologues represented by the formula (bb), ##STR26##where n is a number from 1 to 8; or(b) is a member of (a) substituted with one or more independently selected non-interfering substituents selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.7 -C.sub.12 aralkyl, C.sub.7 -C.sub.12 alkaryl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, phenyl, tolyl, xylyl, biphenylyl, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 alkenyloxy, C.sub.2 -C.sub.6 alkynyloxy, C.sub.2 -C.sub.12 alkoxyalkyl, C.sub.2 -C.sub.12 alkoxyalkyloxy, C.sub.2 -C.sub.12 alkylcarbonyl, C.sub.2 -C.sub.12 alkylcarbonylamino, C.sub.2 -C.sub.12 alkoxyamino, C.sub.2 -C.sub.12 alkoxyaminocarbonyl, C.sub.1 -C.sub.12 alkylamino, C.sub.1 -C.sub.6 alkylthio, C.sub.2 -C.sub.12 alkylthiocarbonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.2 -C.sub.6 haloalkoxy, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.2 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 hydroxyalkyl, --C(O)O(C.sub.1 -C.sub.6 alkyl), --(CH.sub.2).sub.n --O-(C.sub.1 -C.sub.6 alkyl), benzyloxy, phenoxy, phenylthio, --CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, --(CH.sub.2).sub.n --CO.sub.2 H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, --SO.sub.3 H, thioacetal, thiocarbonyl, and C.sub.1 -C.sub.6 carbonyl; where n is from 1 to 8;(c) is the group -(L.sub.1)-R.sub.81 ; where, -(L.sub.1)- is a divalent linking group having the formula; ##STR27##where,R.sub.84 and R.sub.85 are each independently selected from hydrogen, C.sub.1 -C.sub.10 alkyl, carbolxy, carbalkoxy, or halo;p is 1 to 5,Z is a bond, --(CH.sub.2)--, --O--, --N(C.sub.1 -C.sub.10 alkyl)-, --NH--, or --S--; and where R.sub.81 is a group selected from (a) or (b);R.sub.12 is hydrogen, halo, C.sub.1 -C.sub.3 alkyl, C.sub.3 -C.sub.4 cycloalkyl, C.sub.3 -C.sub.4 cycloalkenyl, --O-(C.sub.1 -C.sub.2 alkyl), or --S-(C.sub.1 -C.sub.2 alkyl);R.sub.14 is hydrogen or a group, -(L.sub.a)-(acidic group) wherein -(L.sub.a)- is represented by the formula; ##STR28##where Q is selected from the group --(CH.sub.2)--, --O--, --NH--, and --S--, and R.sub.84 and R.sub.85 are each independently selected from hydrogen, C.sub.1 -C.sub.10 alkyl, aryl, C.sub.1 -C.sub.10 alkaryl, C.sub.1 -C.sub.10 aralkyl, and halo;R.sub.15 is hydrogen or a group, -(La')-(acidic group) wherein -(La')- is represented by the formula; ##STR29##where r is a number from 1 to 7, s is 0 or 1, and Q is selected from the group --(CH.sub.2)--, --O--, --NH--, and --S--, and R.sub.84 ' and R.sub.85 ' are each independently selected from hydrogen, C.sub.1 -C.sub.10 alkyl, aryl, C.sub.1 -C.sub.10 alkaryl, C.sub.1 -C.sub.10 aralkyl, carboxy, carbalkoxy, and halo; provided that at least one of R.sub.14 or R.sub.15 must be the group, -(La)-(acidic group) or -(La')-(acidic group);R.sub.16 is hydrogen, carboxyl or ester thereof;R.sub.17 is selected from hydrogen, non-interfering substituents, selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.7 -C.sub.12 aralkyl, C.sub.7 -C.sub.12 alkaryl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, phenyl, tolyl, xylyl, biphenylyl, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 alkenyloxy, C.sub.2 -C.sub.6 alkynyloxy, C.sub.2 -C.sub.12 alkoxyalkyl, C.sub.2 -C.sub.12 alkoxyalkyloxy, C.sub.2 -C.sub.12 alkylcarbonyl, C.sub.2 -C.sub.12 alkylcarbonylamino, C.sub.2 -C.sub.12 alkoxyamino, C.sub.2 -C.sub.12 alkoxyaminocarbonyl, C.sub.2 -C.sub.12 alkylamino, C.sub.1 -C.sub.6 alkylthio, C.sub.2 -C.sub.12 alkylthiocarbonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.2 -C.sub.6 haloalkoxy, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.2 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 hydroxyalkyl, --C(O)O(C.sub.1 -C.sub.6 alkyl), --(CH.sub.2).sub.n --O-(C.sub.1 -C.sub.6 alkyl), benzyloxy, phenoxy, phenylthio, --CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, --(CH.sub.2).sub.n --CO.sub.2 H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, --SO.sub.3 H, thioacetal, thiocarbonyl, and C.sub.1 -C.sub.6 carbonyl; where n is from 1 to 8.