Pyrimidine bisphosphonate esters and (alkoxymethylphosphinyl)alkyl phosphonic acids as anti-inflammatories

A compound of Formula 1 or 2 or pharmaceutically acceptable salts thereof ##STR4## wherein X is O or S;

• each occurrence of R.sub.1 is the same or different and is selected from the group consisting of H, Na, K, tromethamine, C.sub.1 -C.sub.6 alkyl, CH.sub.2 -phenyl, phenyl (optionally substituted with 1 to 5 NO.sub.2, halo, or C.sub.1 -C.sub.4 alkyl), or both R.sub.1 's on the same phosphorus atom taken together are --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --CH.sub.2 --, or --CH.sub.2 --C(CH.sub.3).sub.2 --CH.sub.2 -- whereby a heterocyclic ring is formed;
• R.sub.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, benzoyloxy, benzyloxy, C.sub.1 -C.sub.6 alkoxy, phenoxy, C.sub.3 -C.sub.7 cycloalkyl, phenyl (optionally substituted with 1 or 2 phenyls, or 1 to 5 halo, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.6 alkylthio), 2-, 4- or 5-pyrimidyl (optionally substituted with 1 or 2 phenyls, or 1 to 3 halo, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 alkoxy, or C.sub.1 -C.sub.6 alkylthio), 2-, 3- or 4-pyridyl (optionally substituted with 1 or 2 phenyl 1 to 4 halo, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.C.sub.6 alkylthio), 1-, or 2-naphthalenyl (optionally substituted with 1 or 2 phenyls, or 1 to 7 halo, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.6 alkoxy or C.sub.1 -C.sub.6 alkylthio);
• R.sub.3 is H, CN, CO.sub.2 R.sub.l, COR.sub.2, CON(R.sub.5).sub.2, halo, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.7 cycloalkyl, or phenyl;
• R.sub.5 is H, C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.7 cycloalkyl;
• R.sub.6 is H, halo, or C.sub.1 -C.sub.6 alkyl;
• R.sub.10 is H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, or phenyl (optionally substituted with 1 or 2 phenyls, or 1 to 5 halos, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.6 alkylthio);
• R.sub.11 is H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, allyl, CH.sub.2 OR.sub.14, CH.sub.2 -phenyl, or phenyl (optionally substituted with 1 to 5 NO.sub.2, halos, or C.sub.1 -C.sub.4 alkyl);
• R.sub.12 is H, C.sub.1 -C.sub.6 alkyl, halo, NO.sub.2 ;
• R.sub.13 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, or phenyl (optionally substituted with 1 to 2 phenyls, or 1 to 5 halos, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.6 alkylthio), 2-, 3- or 4-pyridyl (optionally substituted with 1 to 2 phenyls, or 1 to 4 halos, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.6 alkylthio), 1- or 2- (optionally substituted with 1 to 2 phenyls, or 1 to 7 halos, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.6 alkylthio), piperidinyl, morpholinyl, pyrrolidinyl, N(R.sub.5).sub.2, NHC(O)R.sub.14 or NHC(O)OR.sub.14 ;
• and
• R.sub.14 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, allyl, CH.sub.2 -phenyl, or phenyl (optionally substituted with 1 to 5 NO.sub.2, halos, or C.sub.1 -C.sub.4 alkyl).