Glaxo Wellcome Inc.

Smithkline Beecham Corporation

Burroughs Wellcome Co.

Julius Vass Johnson

William Pendergast

Robert Ferone

Scott Howard Dickerson

Scott H Dickerson

Compounds of formula (I) or salts thereof, wherein the dotted Line represents a single or double bond, R is alkyl or amino optionally substituted by alkyl, alkanoyl or benzyl group; R , R , R and R are the same or different and each is selected from hydrogen, phenyl, halo, nitro, a group S(O) R wherein n is the integer 0, 1 or 2 and R is halo or alkyl or a group NR R wherein R and R are both hydrogen, a group NR R wherein R and R are the same or different and each is hydrogen or alkyl, a group OR wherein R is hydrogen or C of alkyl optionally substituted by halo; a C aliphatic group optionally substituted by a group OR or NR R wherein R and R are the same or different and each is hydrogen or alkyl; or two of R to R are linked together to form a benzo group, or one of R to R is a group X&mdash;Y&mdash;R wherein X is CH , NR , CO or S(O) and Y is CH , NR , O or S(O) , or X&mdash;Y is O, NR , &mdash;CH&boxH;CH&mdash; or N&boxH;N&mdash;, are disclosed as pharmacological agents useful in the treatment of tumours. Pharmaceutical compositions and methods for the preparation of compounds of formula (I) are also described.

Pharmaceutically active benzoquinazoline compounds

Compounds of formula (I) or salts thereof, wherein the dotted line represents a single or double bond, R,is alkyl or amino optionally substituted by alkyl, alkanoyl or benzyl group; R,, R,, R,and R,are the same or different and each is selected from hydrogen, phenyl, halo, nitro, a group S(O),R,wherein n is the integer 0, 1 or 2 and R,is halo or alkyl or a group NR,R,wherein R,and R,are both hydrogen, a group NR,R,wherein R,and R,are the same or different and each is hydrogen or alkyl, a group OR,wherein R,is hydrogen or C,of alkyl optionally substituted by halo; a C,aliphatic group optionally substituted by a group OR,or NR,R,wherein R,and R,are the same or different and each is hydrogen or alkyl; or two of R,to R,are linked together to form a benzo group, or one of R,to R,is a group X&mdash;Y&mdash;R,wherein X is CH,, NR,, CO or S(O),and Y is CH,, NR,, O or S(O),, or X&mdash;Y is O, NR,, &mdash;CH&boxH;CH&mdash; or N&boxH;N&mdash;, are disclosed as pharmacological agents useful in the treatment of tumours. Pharmaceutical compositions and methods for the preparation of compounds of formula (I) are also described.

Compounds of the formula (I) or salts thereof, ##STR1## wherein the dotted line represents a single or double bond, R.sup.1 is alkyl or amino optionally substituted by alkyl, alkanoyl or benzyl group: R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same or different and each is selected from hydrogen, phenyl, halo, nitro, a group S(O).sub.n R.sup.8 wherein n is the integer 0, 1 or 2 and R.sup.8 is halo or alkyl or a group NR.sup.9 R.sup.10 are both hydrogen, a group NR.sup.11 R.sup.12 wherein R.sup.11 and R.sup.12 are the same or different and each is hydrogen or alkyl, a group OR.sup.13 wherein R.sup.13 is hydrogen or C.sub.1-4 alkyl substituted by halo; a C.sub.1-4 aliphatic group optionally substituted by a group OR.sup.14 or NR.sup.14 R.sup.15 wherein R.sup.14 and R.sup.15 are the same or different and each is hydrogen or alkyl; ot two of R.sup.2 to R.sup.5 are linked together to form a benzp group, one of R.sup.2 to R.sup.3 is a group X--Y--R.sup.16 wherein X is CH.sub.2, NR.sup.17, CO, or S(O).sub.m and Y is CH.sub.2, NR.sup.17, O or S(O).sub.m, or X--Y is CH.sub.2,NR.sup.17, --CH.dbd.CH-- or --N.dbd.N--, are disclosed as pharmacological agents useful in the treatment of tumors. Pharmaceutical compositions and methods for the preparation of compounds of formula (I) are also disclosed.

The present invention relates to novel benzoquinazoline thymidylate synthase inhibitors, to pharmaceutical formulations containing them and to their use in medicine.

Growing community of inventors

Chapel Hill, NC, United States of America

Julius Vass Johnson