Compounds and matrices for use in bone growth and repair

A compound of Formula IIa:

• wherein R″ is independently cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl or tetrahydrothien-3-yl;
• X is sulfur;
• and
• each R′″ is independently cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.

A bone graft material prepared by combining isolated cells capable of differentiating into bone cells, a calcium phosphate matrix, and a compound into a surgical cage, wherein the compound has the structure of Formula II or Formula IIa:

• wherein R1 and R7 are independently methylcarbonyl, trideuteromethylcarbonyl, trifluoromethylcarbonyl, 2,2,2-trifluoroethylcarbonyl, propylcarbonyl, iso-propylcarbonyl, butylcarbonyl, sec-butylcarbonyl, iso-butylcarbonyl, tert-butylcarbonyl, pentylcarbonyl, 2-pentylcarbonyl, 3-pentylcarbonyl, 1,1-dimethylpropylcarbonyl, 1,2-dimethylpropylcarbonyl, 2-methoxyethylcarbonyl, 2-ethoxylethylcarbonyl, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, azacycloprop-2-ylcarbonyl, azacyclobut-2-ylcarbonyl, azacyclopent-2-ylcarbonyl, azacyclohex-2-ylcarbonyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 2,3-dimethoxyphenylcarbonyl, 2,4-dimethoxyphenylcarbonyl, 2,5-dimethoxyphenylcarbonyl, 2,6-dimethoxyphenylcarbonyl, 3,5-dimethoxyphenylcarbonyl, 2,3,4-trimethoxyphenylcarbonyl, 2,3,5-trimethoxyphenylcarbonyl, 2,3,6-trimethoxyphenylcarbonyl, 2,4,5-trimethoxyphenylcarbonyl, 2,4,6-trimethoxylphenylcarbonyl, 3,4,5-trimethoxyphenylcarbonyl, 2-ethoxyphenylcarbonyl, 3-ethoxyphenylcarbonyl, 4-ethoxyphenylcarbonyl, 2,3-diethoxyphenylcarbonyl, 2,4-diethoxyphenylcarbonyl, 2,5-diethoxyphenylcarbonyl, 2,6-diethoxyphenylcarbonyl, 3,4-diethoxyphenylcarbonyl, 3,5-diethoxyphenylcarbonyl, 2,3,4-triethoxyphenylcarbonyl, 2,3,5-triethoxyphenylcarbonyl, 2,3,6-triethoxyphenylcarbonyl, 2,4,5-triethoxyphenylcarbonyl, 2,4,6-triethoxylphenylcarbonyl, 3,4,5-triethoxyphenylcarbonyl, 2,3-dimethylphenylcarbonyl, 2,4-dimethylphenylcarbonyl, 2,5-dimethylphenylcarbonyl, 2,6-dimethylphenylcarbonyl, 3,4-dimethylphenylcarbonyl, 3,5-dimethylphenylcarbonyl, 2-ethylphenylcarbonyl, 3-ethylphenylcarbonyl, 2,3-diethylphenylcarbonyl, 2,4-diethylphenylcarbonyl, 2,5-diethylphenylcarbonyl, 2,6-diethylphenylcarbonyl, 3,4-diethylphenylcarbonyl, 3,5-diethylphenylcarbonyl, 2,3-difluorophenylcarbonyl, 2,4-difluorophenylcarbonyl, 2,5-difluorophenylcarbonyl, 2,6-difluorophenylcarbonyl, 3,5-difluorophenylcarbonyl, perfluorophenylcarbonyl;
• R4 and R′ substituents are independently hydro, methyl, trideuteromethyl, ethyl, 2,2,2-trifluoroethyl, propyl, 2-propyl, butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, 2-pentyl, 3-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propyloxy, 2-propyloxy, butoxy, sec-butoxy, iso-butoxy, tert-butoxy, pentoxy, 2-pentoxy, 3-pentoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, fluoro, chloro, amino, dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, N-azacycloprop-1-yl, N-azacyclobut-1-yl, N-pyrrolidino, N-piperidino, N-piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl or N-propylpiperazinyl;
• R″ is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl;
• X is oxygen or sulfur;
• and
• each R′″ is independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

A method for increasing adherence of cells to calcium phosphate materials by treatment of cells in the presence of a calcium phosphate material with a compound, wherein the compound has the structure of Formula II or Formula IIa:

• wherein R1 and R7 are independently methylcarbonyl, trideuteromethylcarbonyl, trifluoromethylcarbonyl, 2,2,2-trifluoroethylcarbonyl, propylcarbonyl, iso-propylcarbonyl, butylcarbonyl, sec-butylcarbonyl, iso-butylcarbonyl, tert-butylcarbonyl, pentylcarbonyl, 2-pentylcarbonyl, 3-pentylcarbonyl, 1,1-dimethylpropylcarbonyl, 1,2-dimethylpropylcarbonyl, 2-methoxyethylcarbonyl, 2-ethoxylethylcarbonyl, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, azacycloprop-2-ylcarbonyl, azacyclobut-2-ylcarbonyl, azacyclopent-2-ylcarbonyl, azacyclohex-2-ylcarbonyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 2,3-dimethoxyphenylcarbonyl, 2,4-dimethoxyphenylcarbonyl, 2,5-dimethoxyphenylcarbonyl, 2,6-dimethoxyphenylcarbonyl, 3,5-dimethoxyphenylcarbonyl, 2,3,4-trimethoxyphenylcarbonyl, 2,3,5-trimethoxyphenylcarbonyl, 2,3,6-trimethoxyphenylcarbonyl, 2,4,5-trimethoxyphenylcarbonyl, 2,4,6-trimethoxylphenylcarbonyl, 3,4,5-trimethoxyphenylcarbonyl, 2-ethoxyphenylcarbonyl, 3-ethoxyphenylcarbonyl, 4-ethoxyphenylcarbonyl, 2,3-diethoxyphenylcarbonyl, 2,4-diethoxyphenylcarbonyl, 2,5-diethoxyphenylcarbonyl, 2,6-diethoxyphenylcarbonyl, 3,4-diethoxyphenylcarbonyl, 3,5-diethoxyphenylcarbonyl, 2,3,4-triethoxyphenylcarbonyl, 2,3,5-triethoxyphenylcarbonyl, 2,3,6-triethoxyphenylcarbonyl, 2,4,5-triethoxyphenylcarbonyl, 2,4,6-triethoxylphenylcarbonyl, 3,4,5-triethoxyphenylcarbonyl, 2,3-dimethylphenylcarbonyl, 2,4-dimethylphenylcarbonyl, 2,5-dimethylphenylcarbonyl, 2,6-dimethylphenylcarbonyl, 3,4-dimethylphenylcarbonyl, 3,5-dimethylphenylcarbonyl, 2-ethylphenylcarbonyl, 3-ethylphenylcarbonyl, 2,3-diethylphenylcarbonyl, 2,4-diethylphenylcarbonyl, 2,5-diethylphenylcarbonyl, 2,6-diethylphenylcarbonyl, 3,4-diethylphenylcarbonyl, 3,5-diethylphenylcarbonyl, 2,3-difluorophenylcarbonyl, 2,4-difluorophenylcarbonyl, 2,5-difluorophenylcarbonyl, 2,6-difluorophenylcarbonyl, 3,5-difluorophenylcarbonyl, perfluorophenylcarbonyl;
• R4 and R′ substituents are independently hydro, methyl, trideuteromethyl, ethyl, 2,2,2-trifluoroethyl, propyl, 2-propyl, butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, 2-pentyl, 3-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propyloxy, 2-propyloxy, butoxy, sec-butoxy, iso-butoxy, tert-butoxy, pentoxy, 2-pentoxy, 3-pentoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, fluoro, chloro, amino, dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, N-azacycloprop-1-yl, N-azacyclobut-1-yl, N-pyrrolidino, N-piperidino, N-piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl or N-propylpiperazinyl;
• R″ is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl;
• X is oxygen or sulfur;
• and
• each R′″ is independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.