Pyrimidine derivatives and methods of making and using these derivatives

Claim 1

A compound, and pharmaceutically acceptable salts thereof, having the formula: ##STR68## wherein X and Y are the same or different and are selected from the group consisting of OH, NH 2 , H and CH 3 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z 2 and Z 3 are different and are selected from the group consisting of R 4 and ##STR69## where Z 2 is R 4 when Z 3 is ##STR70## and Z 2 is ##STR71## when Z 3 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of CH, nitrogen, N--CH 2 , CH 2 --N, CH 2 --CH 2 , oxygen, sulfur, sulfoxide, sulfone and zero, but B is not N--CH 2 when A is CH and Z 3 is R 4 ; wherein A is not zero when B is CH 2 --CH 2 and Z 3 is R 4 ; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is zero, oxygen, sulfur, sulfoxide or sulfone; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero when Z 2 is R 4 , and R 3 is selected from the group consisting of a lower alkyl group and zero when Z 3 is R 4 , and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 8 is selected from the group consisting of naphthyl, mono-, di- and tri-substituted naphthyl, thionaphthyl, thiophenyl and hydroxyphenyl when R 1 is hydrogen and R 4 is hydrogen; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, pyridine and p-aroyl-L-glutamate when R 1 is a lower alkyl group and R 4 is hydrogen; wherein R 8 is selected from the group consisting of pyridine, phenyl, mono-, di- and tri-substituted phenyl, naphthyl, and mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is zero; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is hydrogen and R 4 is a lower alkyl group; and wherein R 8 is not p-benzoyl-L-glutamate or pyridine when X is OH, A is zero, B is sulfur, R 4 is methyl and R 5 is hydrogen, and R 8 is not p-benzoyl-L-glutamate when X is OH, A is CH, B is CH, R 4 is hydrogen and R 5 is hydrogen; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons.

Claim 3

A method of therapeutically treating a patient for an illness comprising the steps of: a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: ##STR72## wherein X and Y are the same or different and are selected from the group consisting of OH, NH 2 , H and CH 3 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z 2 and Z 3 are different and are selected from the group consisting of R 4 and ##STR73## where Z 2 is R 4 when Z 3 is ##STR74## and Z 2 is ##STR75## when Z 3 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of CH, nitrogen, N--CH 2 , CH 2 --N, CH 2 --CH 2 , oxygen, sulfur, sulfoxide, sulfone and zero, but B is not N--CH 2 when A is CH and Z 3 is R 4 ; wherein A is not zero when B is CH 2 --CH 2 and Z 3 is R 4 ; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is zero, oxygen, sulfur, sulfoxide or sulfone; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero when Z 2 is R 4 and R 3 is selected from the group consisting of a lower alkyl group and zero when Z 3 is R 4 , and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 8 is selected from the group consisting of naphthyl, mono-, di- and tri-substituted naphthyl, thionaphthyl, thiophenyl and hydroxyphenyl when R 1 is hydrogen and R 4 is hydrogen; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, pyridine and p-aroyl-L-glutamate when R 1 is a lower alkyl group and R 4 is hydrogen; wherein R 8 is selected from the group consisting of pyridine, phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is zero; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is hydrogen and R 4 is a lower alkyl group; wherein R 8 is not p-benzoyl-L-glutamate or pyridine when X is OH, A is zero, B is sulfur, R 4 is methyl and R 5 is hydrogen, and R 8 is not p-benzoyl-L-glutamate when X is OH, A is CH, B is CH, R 4 is hydrogen and R 5 is hydrogen; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.

Claim 4

A method of therapeutically treating a patient for an illness comprising the steps of: a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: ##STR72## wherein X and Y are the same or different and are selected from the group consisting of OH, NH 2 , H and CH 3 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z 2 and Z 3 are different and are selected from the group consisting of R 4 and ##STR73## where Z 2 is R 4 when Z 3 is ##STR74## and Z 2 is ##STR75## when Z 3 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of CH, nitrogen, N--CH 2 , CH 2 --N, CH 2 --CH 2 , oxygen, sulfur, sulfoxide, sulfone and zero, but B is not N--CH 2 when A is CH and Z 3 is R 4 ; wherein A is not zero when B is CH 2 --CH 2 and Z 3 is R 4 ; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is zero, oxygen, sulfur, sulfoxide or sulfone; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero when Z 2 is R 4 and R 3 is selected from the group consisting of a lower alkyl group and zero when Z 3 is R 4 , and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 8 is selected from the group consisting of naphthyl, mono-, di- and tri-substituted naphthyl, thionaphthyl, thiophenyl and hydroxyphenyl when R 1 is hydrogen and R 4 is hydrogen; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, pyridine and p-aroyl-L-glutamate when R 1 is a lower alkyl group and R 4 is hydrogen; wherein R 8 is selected from the group consisting of pyridine, phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is zero; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is hydrogen and R 4 is a lower alkyl group; wherein R 8 is not p-benzoyl-L-glutamate or pyridine when X is OH, A is zero, B is sulfur, R 4 is methyl and R 5 is hydrogen, and R 8 is not p-benzoyl-L-glutamate when X is OH, A is CH, B is CH, R 4 is hydrogen and R 5 is hydrogen; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.

Claim 11

A method of prophylactically treating a patient for an illness comprising the steps of: a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: ##STR76## wherein X and Y are the same or different and are selected from the group consisting of OH, NH 2 , H and CH 3 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z 2 and Z 3 are different and are selected from the group consisting of R 4 and ##STR77## where Z 2 is R 4 when Z 3 is ##STR78## and Z 2 is ##STR79## when Z 3 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of CH, nitrogen, N--CH 2 , CH 2 --N, CH 2 --CH 2 , oxygen, sulfur, sulfoxide, sulfone and zero, but B is not N--CH 2 , when A is CH and Z 3 is R 4 ; wherein A is not zero when B is CH 2 --CH 2 and Z 3 is R 4 ; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is zero, oxygen, sulfur, sulfoxide or sulfone; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero when Z 2 is R 4 and R 3 is selected from the group consisting of a lower alkyl group and zero when Z 3 is R 4 , and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 8 is selected from the group consisting of naphthyl, mono-, di- and tri-substituted naphthyl, thionaphthyl, thiophenyl and hydroxyphenyl when R 1 is hydrogen and R 4 is hydrogen; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, pyridine and p-aroyl-L-glutamate when R 1 is a lower alkyl group and R 4 is hydrogen; wherein R 8 is selected from the group consisting of pyridine, phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is zero; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is hydrogen and R 4 is a lower alkyl group; wherein R 8 is not p-benzoyl-L-glutamate or pyridine when X is OH, A is zero, B is sulfur, R 4 is methyl and R 5 is hydrogen, and R 8 is not p-benzoyl-L-glutamate when X is OH, A is CH, B is CH, R 4 is hydrogen and R 5 is hydrogen; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of cancer and infection caused by Pneumocystis carinii and Toxoplasmosis gondii.

Claim 12

A method of prophylactically treating a patient for an illness comprising the steps of: a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: ##STR76## wherein X and Y are the same or different and are selected from the group consisting of OH, NH 2 , H and CH 3 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z 2 and Z 3 are different and are selected from the group consisting of R 4 and ##STR77## where Z 2 is R 4 when Z 3 is ##STR78## and Z 2 is ##STR79## when Z 3 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of CH, nitrogen, N--CH 2 , CH 2 --N, CH 2 --CH 2 , oxygen, sulfur, sulfoxide, sulfone and zero, but B is not N--CH 2 , when A is CH and Z 3 is R 4 ; wherein A is not zero when B is CH 2 --CH 2 and Z 3 is R 4 ; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is zero, oxygen, sulfur, sulfoxide or sulfone; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero when Z 2 is R 4 and R 3 is selected from the group consisting of a lower alkyl group and zero when Z 3 is R 4 , and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 8 is selected from the group consisting of naphthyl, mono-, di- and tri-substituted naphthyl, thionaphthyl, thiophenyl and hydroxyphenyl when R 1 is hydrogen and R 4 is hydrogen; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, pyridine and p-aroyl-L-glutamate when R 1 is a lower alkyl group and R 4 is hydrogen; wherein R 8 is selected from the group consisting of pyridine, phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is zero; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is hydrogen and R 4 is a lower alkyl group; wherein R 8 is not p-benzoyl-L-glutamate or pyridine when X is OH, A is zero, B is sulfur, R 4 is methyl and R 5 is hydrogen, and R 8 is not p-benzoyl-L-glutamate when X is OH, A is CH, B is CH, R 4 is hydrogen and R 5 is hydrogen; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of cancer and infection caused by Pneumocystis carinii and Toxoplasmosis gondii.