Aryl-substituted rhodanine derivatives

A method of treating inflammation and arthritis in mammals which comprises administering to said mammal an effective amount of a compound of the formula (II) ##STR54## wherein:

• R.sup.1a and R.sup.2a are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR55## R.sup.3a is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.4a and R.sup.5a are each hydrogen or when taken together form a bond;
• R.sup.6a and R.sup.7a when taken together are .dbd.S, or when one of R.sup.6a and R.sup.7a is hydrogen the other is --OH or --SCH.sub.3 ;
• X.sup.a is ##STR56## where m is 0, 1 or 2;
• and Q.sup.a is NR.sup.8a where R.sup.8a is C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, --SO.sub.2 CH.sub.3 or --(CH.sub.2).sub.n --Y.sup.a, where n is an integer from 0 to 3, both inclusive, and Y.sup.a is cyano, or OR.sup.9a, ##STR57## tetrazolyl, --NR.sup.11a R.sup.12a, --SH, --S(C.sub.1 -C.sub.4 alkyl) or ##STR58## where R.sup.9a is hydrogen, C.sub.1 -C.sub.4 alkyl, or ##STR59## R.sup.10a is C.sub.1 -C.sub.4 alkyl or --NH.sub.2 ;
• R.sup.11a and R.sup.12a are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --(CH.sub.2).sub.q OH, --(CH.sub.2).sub.q --N(C.sub.1 -C.sub.4 alkyl).sub.2, --(CH.sub.2).sub.q --S (C.sub.1 -C.sub.4 alkyl) or ##STR60## where n is as defined above and q is an integer from 1 to 6, both inclusive;
• or R.sup.11a and R.sup.12a taken together form a morpholinyl, piperidinyl, piperazinyl or an N-methylpiperazinyl ring.

A pharmaceutical composition comprising a compound of formula II. ##STR61## wherein:

• R.sup.1a is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 alkyl ##STR62## R.sup.2a is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR63## R.sup.3a is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.4a and R.sup.5a are each hydrogen or when taken together form a bond;
• R.sup.6a and R.sup.7a when taken together are .dbd.S, or when one of R.sup.6a and R.sup.7a is hydrogen the other is --OH or --SCH.sub.3 ;
• X.sup.a is ##STR64## where m is 0, 1 or 2;
• and Q.sup.a is NR.sup.8a where R.sup.8a is C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, --SO.sub.2 CH.sub.3 or --(CH.sub.2).sub.n --Y.sup.a, where n is an integer from 0 to 3, both inclusive, and Y.sup.a is cyano, or OR.sup.9a, ##STR65## tetrazolyl, --NR.sup.11a R.sup.12a, --SH, --S(C.sub.1 -C.sub.4 alkyl) or ##STR66## where R.sup.9a is hydrogen, C.sub.1 -C.sub.4 alkyl, or ##STR67## R.sup.10a is C.sub.1 -C.sub.4 alkyl, --NH.sub.2 ;
• R.sup.11a and R.sup.12a are each independently hydrogen, C.sub.1 -C.sub.5 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --(CH.sub.2).sub.q OH, --(CH.sub.2).sub.q --N(C.sub.1 -C.sub.4 alkyl).sub.2, --(CH.sub.2).sub.q --S(C.sub.1 -C.sub.4 alkyl) or ##STR68## where n is as defined above and q is an integer from 1 to 6, both inclusive;
• or R.sup.11a and R.sup.12a taken together form a morpholinyl, piperidinyl, piperazinyl or an N-methylpiperazinyl ring in association with one or more pharmaceutically acceptable diluents, excipients or carriers therefor.

A method of preventing ischemia-induced cell damage in mammals which comprises administering to said mammal an effective amount of a compound of the formula (III) ##STR69## wherein:

• R.sup.1b and R.sup.2b are each independently C.sub.1 -C.sub.6 alkyl;
• R.sup.3b and R.sup.4b are each hydrogen or when taken together form a bond;
• R.sup.5b and R.sup.6b when taken together are .dbd.O;
• and
• X.sup.b is ##STR70## where m is 0, 1 or 2;
• R.sup.7b is hydrogen, C.sub.1 -C.sub.6 alkyl, or --(CH.sub.2).sub.n --Y.sup.b, where n is an integer from 0 to 3, both inclusive and Y.sup.b is cyano, OR.sup.8b, ##STR71## --SH, --S(C.sub.1 -C.sub.4 alkyl), tetrazolyl, --NR.sup.10b R.sup.11b or ##STR72## where R.sup.8b is hydrogen, C.sub.1 -C.sub.4 alkyl, or ##STR73## R.sup.9b is --NH.sub.2 or --OH;
• and R.sup.10b and R.sup.11b are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl or C.sub.2 -C.sub.6 alkynyl.

A compound of the formula (I):

• ##STR74## wherein:
• R.sup.1 is methyl, ethyl, hexyl, isohexyl, neohexyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR75## R.sup.2 is hydrogen, methyl, ethyl, hexyl, isohexyl, neophexyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR76## R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.4 and R.sup.5 are each hydrogen, or when taken together form a bond;
• R.sup.6 and R.sup.7 when taken together are .dbd.S, or when one of R.sup.6 or R.sup.7 is hydrogen, the other is --OH or --SCH.sub.3 ;
• X is ##STR77## where m is 0, 1 or 2;
• and Q is NR.sup.8 where R.sup.8 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, --SO.sub.2 CH.sub.3 or --(CH.sub.2).sub.n --Y, where n is an integer from 0 to 3 both inclusive and Y is cyano OR.sup.9, ##STR78## tetrazolyl, --NR.sup.11 R.sup.12, --SH, --S(C.sub.1 -C.sub.4 alkyl) or ##STR79## where R.sup.9 is hydrogen, C.sub.1 -C.sub.4 alkyl, tosyl, or ##STR80## R.sup.10 is C.sub.1 -C.sub.4 alkyl or --NH.sub.2 ;
• R.sup.11 and R.sup.12 are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --(CH.sub.2).sub.q OH,--(CH.sub.2).sub.q --N(C.sub.1 -C.sub.4 alkyl).sub.2, --(CH.sub.2).sub.q --S(C.sub.1 -C.sub.4 alkyl) or ##STR81## where q is an integer from 1 to 6, both inclusive, and n is as defined above;
• or R.sup.11 and R.sup.12 taken together form a morpholinyl, piperidinyl, piperazinyl or an N-methylpiperazinyl ring;
• with the proviso that when R.sup.3 is hydrogen and R.sup.4 and R.sup.5 taken together form a bond and R.sup.8 is hydrogen, R.sup.6 and R.sup.7 may not be .dbd.S.

A compound of the formula (I):

• ##STR82## wherein:
• R.sup.1 is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR83## R.sup.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR84## R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.4 and R.sup.5 are each hydrogen, or when taken together form a bond;
• R.sup.6 and R.sup.7 when taken together are .dbd.S, or when one of R.sup.6 or R.sup.7 is hydrogen, the other is --OH or --SCH.sub.3 ;
• X is ##STR85## where m is 1 or 2;
• and Q is NR.sup.8 where R.sup.8 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, --SO.sub.2 CH.sub.3 or --(CH.sub.2).sub.n --Y, where n is an integer from 0 to 3, both inclusive, and Y is cyano, OR.sup.9, ##STR86## tetrazolyl, --NR.sup.11 R.sup.12, --SH, --S(C.sub.1 -C.sub.4 alkyl) or ##STR87## where R.sup.9 is hydrogen, C.sub.1 -C.sub.4 alkyl, tosyl, or ##STR88## R.sup.10 is C.sub.1 -C.sub.4 alkyl or --NH.sub.2 ;
• R.sup.11 and R.sup.12 are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --(CH.sub.2).sub.q OH,--(CH.sub.2).sub.q --N(C.sub.1 -C.sub.4 alkyl).sub.2, --(CH.sub.2).sub.q --S(C.sub.1 -C.sub.4 alkyl) or ##STR89## where q is an integer from 1 to 6, both inclusive, and n is as defined above;
• or R.sup.11 and R.sup.12 taken together form a morpholinyl, piperidinyl, piperazinyl or an N-methylpiperazinyl ring;
• with the proviso that when R.sup.3 is hydrogen and R.sup.4 and R.sup.5 taken together form a bond and R.sup.8 is hydrogen, R.sup.6 and R.sup.7 may not be .dbd.S.

A compound of the formula (I):

• ##STR90## wherein:
• R.sup.1 and R.sup.2 are each 1,1-dimethylethyl;
• R.sup.3 i s hydrogen;
• R.sup.4 and R.sup.5 are each hydrogen, or when taken together, form a bond;
• R.sup.6 and R.sup.7, when taken together are .dbd.S;
• X is ##STR91## where m is 0;
• and Q is NR.sup.8 where R.sup.8 is hydrogen, C.sub.1 -C.sub.4 alkyl, with the proviso that when R.sup.4 and R.sup.5 taken together form a bond, R.sup.8 must be C.sub.1 -C.sub.4 alkyl.

A method of treating inflammation and arthritis in mammals which comprises administering to said mammal an effective amount of a compound of the formula (II) ##STR92## wherein:

• R.sup.1a and R.sup.2a are each independently hydrogen, methyl, ethyl, hexyl, isohexyl, neohexyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR93## R.sup.3a is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.4a and R.sup.5a are each hydrogen or when taken together form a bond;
• R.sup.6a and R.sup.7a when taken together are .dbd.S, or when one of R.sup.6a and R.sup.7a is hydrogen the other is --OH or --SCH.sub.3 ;
• X.sup.a is ##STR94## where m is 0, 1 or 2;
• and Q.sup.a is NR.sup.8a where R.sup.8a is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, --SO.sub.2 CH.sub.3 or --(CH.sub.2).sub.n --Y.sup.a, where n is an integer from 0 to 3, both inclusive, and Y.sup.a is cyano, or OR.sup.9a, ##STR95## tetrazolyl, --NR.sup.11a R.sup.12a, --SH, --S (C.sub.1 -C.sub.4 alkyl) or ##STR96## where R.sup.9a is hydrogen, C.sub.1 -C.sub.4 alkyl , or ##STR97## R.sup.10a is C.sub.1 -C.sub.4 alkyl or --NH.sub.2 ;
• R.sup.11a and R.sup.12a are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --(CH.sub.2).sub.q OH, --(CH.sub.2).sub.q --N(C.sub.1 -C.sub.4 alkyl).sub.2, --(CH.sub.2).sub.q --S(C.sub.1 -C.sub.4 alkyl) or ##STR98## where n is as defined above and q is an integer from 1 to 6, both inclusive;
• or R.sup.11a and R.sup.12a taken together form a morpholinyl, piperidinyl, piperazinyl or an N-methylpiperazinyl ring.

A method of treating inflammation and arthritis in mammals which comprises administering to said mammal an effective amount of a compound of the formula (II) ##STR99## wherein:

• R.sup.1a and R.sup.2a are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR100## R.sup.3a is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.4a and R.sup.5a are each hydrogen or when taken together form a bond;
• R.sup.6a and R.sup.7a when taken together are .dbd.S, or when one of R.sup.6a and R.sup.7a is hydrogen the other is --OH or --SCH.sub.3 ;
• X.sup.a is ##STR101## where m is 1 or 2;
• and Q.sup.a is NR.sup.8a where R.sup.8a is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, --SO.sub.2 CH.sub.3 or --(CH.sub.2).sub.n --Y.sup.a, where n is an integer from 0 to 3, both inclusive, and Y.sup.a is cyano, or OR.sup.9a, ##STR102## tetrazolyl, --NR.sup.11a R.sup.12a, --SH, --S(C.sub.1 -C.sub.4 alkyl) or ##STR103## where R.sup.9a is hydrogen, C.sub.1 -C.sub.4 alkyl , or ##STR104## R.sup.10a is C.sub.1 -C.sub.4 alkyl or --NH.sub.2 ;
• R.sup.11a and R.sup.12a are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --(CH.sub.2).sub.q OH, --(CH.sub.2).sub.q --N(C.sub.1 -C.sub.4 alkyl).sub.2, --(CH.sub.2).sub.q --S(C.sub.1 -C.sub.4 alkyl) or ##STR105## where n is as defined above and q is an integer from 1 to 6, both inclusive;
• or R.sup.11a and R.sup.12a taken together form a morpholinyl, piperidinyl, piperazinyl or an N-methylpiperazinyl ring.

A method of treating inflammation and arthritis in mammals which comprises administering to said mammal an effective amount of a compound of the formula (I):

• ##STR106## wherein:
• R.sup.1 and R.sup.2 are each 1,1-dimethylethyl;
• R.sup.3 is hydrogen;
• R.sup.4 and R.sup.5 are each hydrogen, or when taken together, form a bond;
• R.sup.6 and R.sup.7, when taken together are .dbd.S;
• X is ##STR107## where m is 0;
• and Q is NR.sup.8 where R.sup.8 is hydrogen, C.sub.1 -C.sub.4 alkyl, with the proviso that when R.sup.4 and R.sup.5 taken together form a bond, R.sup.8 must be C.sub.1 -C.sub.4 alkyl.

A pharmaceutical composition comprising a compound of the formula (II) ##STR108## wherein:

• R.sup.1a is methyl, ethyl, hexyl, isohexyl, neohexyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR109## R.sup.2a is hydrogen, methyl, ethyl, hexyl, isohexyl, neohexyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR110## R.sup.3a is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.4a and R.sup.5a are each hydrogen or when taken together form a bond;
• R.sup.6a and R.sup.7a when taken together are .dbd.S, or when one of R.sup.6a and R.sup.7a is hydrogen the other is --OH or --SCH.sub.3 ;
• X.sup.a is ##STR111## where m is 0, 1 or 2;
• and Q.sup.a is NR.sup.8a where R.sup.8a is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, --SO.sub.2 CH.sub.3 or --(CH.sub.2).sub.n --Y.sup.a, where n is an integer from 0 to 3, both inclusive, and Y.sup.a is cyano, or OR.sup.9a, ##STR112## tetrazolyl, --NR.sup.11a R.sup.12a, --SH, --S(C.sub.1 -C.sub.4 alkyl) or ##STR113## where R.sup.9a is hydrogen, C.sub.1 -C.sub.4 alkyl , or ##STR114## R.sup.10a is C.sub.1 -C.sub.4 alkyl or --NH.sub.2 ;l R.sup.11a and R.sup.12a are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --(CH.sub.2).sub.q OH, --(CH.sub.2).sub.q --N(C.sub.1 -C.sub.4 alkyl).sub.2, --(CH.sub.2).sub.q --S(C.sub.1 -C.sub.4 alkyl) or ##STR115## where n is as defined above and q is an integer from 1 to 6, both inclusive;
• or R.sup.11a and R.sup.12a taken together form a morpholinyl, piperidinyl, piperazinyl or an N-methylpiperazinyl ring in association with one or more pharmaceutically acceptable diluents, excipients or carriers therefor.

A pharmaceutical composition comprising a compound of the formula (II) ##STR116## wherein:

• R.sup.1a is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR117## R.sup.2a is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.4 ##STR118## R.sup.3a is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.4a and R.sup.5a are each hydrogen or when taken together form a bond;
• R.sup.6a and R.sup.7a when taken together are .dbd.S, or when one of R.sup.6a and R.sup.7a is hydrogen the other is --OH or --SCH.sub.3 ;
• X.sup.a is ##STR119## where m is 1 or 2;
• and Q.sup.a is NR.sup.8a where R.sup.8a is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, --SO.sub.2 CH.sub.3 or --(CH.sub.2).sub.n --Y.sup.a, where n is an integer from 0 to 3, both inclusive, and Y.sup.a is cyano, or OR.sup.9a, ##STR120## tetrazolyl, --NR.sup.11a R.sup.12a, --SH, --S(C.sub.1 -C.sub.4 alkyl) or ##STR121## where R.sup.9a is hydrogen, C.sub.1 -C.sub.4 alkyl , or ##STR122## R.sup.10a is C.sub.1 -C.sub.4 alkyl or --NH.sub.2 ;
• R.sup.11a and R.sup.12a are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --(CH.sub.2).sub.q OH, --(CH.sub.2).sub.q --N(C.sub.1 -C.sub.4 alkyl).sub.2, --(CH.sub.2).sub.q --S(C.sub.1 -C.sub.4 alkyl) or ##STR123## where n is as defined above and q is an integer from 1 to 6, both inclusive;
• or R.sup.11a and R.sup.12a taken together form a morpholinyl, piperidinyl, piperazinyl or an N-methylpiperazinyl ring in association with one or more pharmaceutically acceptable diluents, excipients or carriers therefor.

A pharmaceutical composition comprising a compound of the formula (I):

• ##STR124## wherein:
• R.sup.1 and R.sup.2 are each 1,1-dimethylethyl;
• R.sup.3 is hydrogen;
• R.sup.4 and R.sup.5 are each hydrogen, or when taken together, form a bond;
• R.sup.6 and R.sup.7, when taken together are .dbd.S;
• X is ##STR125## where m is 0;
• and Q is NR.sup.8 where R.sup.8 is hydrogen, C.sub.1 -C.sub.4 alkyl, with the proviso that when R.sup.4 and R.sup.5 taken together form a bond, R.sup.8 must be C.sub.1 -C.sub.4 alkyl.