Synthesis of quinazolinone libraries and derivatives thereof

A combinatorial library of quinazolinone derivatives comprising quinazolinone derivatives of the structure:

• ##STR41## wherein:
• R.sup.1 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.6 alkyl;
• C.sub.1 to C.sub.6 substituted alkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
• R.sup.2 is selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, cyano, nitro, C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.1 to C.sub.4 alkoxy, C.sub.1 to C.sub.7 acyloxy, C.sub.1 to C.sub.7 acyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.3 to C.sub.7 cycloalkenyl, C.sub.3 to C.sub.7 substituted cycloalkenyl, a heterocyclic ring, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, cyclic C.sub.2 to C.sub.10 alkylene, substituted cyclic C.sub.2 to C.sub.10 alkylene, cyclic C.sub.2 to C.sub.10 heteroalkylene, substituted cyclic C.sub.2 to C.sub.10 heteroalkylene, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, (monosubstituted)amino, protected (monosubstituted)amino, (disubstituted)amino, carboxamide, protected carboxamide, C.sub.1 to C.sub.4 alkylthio, C.sub.1 to C.sub.4 alkylsulfonyl, methylsulfonylamino, C1 to C4 alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl, and substituted phenylsulfonyl;
• R.sup.4 is selected from the group consisting of C.sub.1 to C.sub.6 alkyl;
• C.sub.1 to C.sub.6 substituted alkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, a heterocyclic ring, and a cyclic C.sub.2 to C.sub.10 heteroalkylene;
• Y may be absent and, if present, is selected from the group consisting of carboxylic acid, carboxamide, protected carboxamide, an amino resin, a hydroxy resin, methylamine, and N-alkylated methylamine.

A combinatorial library of 1,2-dihydro quinazolinone derivatives comprising quinazolinone derivatives of the structure:

• ##STR42## wherein:
• R.sup.1 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.6 alkyl;
• C.sub.1 to C.sub.6 substituted alkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
• R.sup.2 is selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, cyano, nitro, C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.1 to C.sub.4 alkoxy, C.sub.1 to C.sub.7 acyloxy, C.sub.1 to C.sub.7 acyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.3 to C.sub.7 cycloalkenyl, C.sub.3 to C.sub.7 substituted cycloalkenyl, a heterocyclic ring, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, cyclic C.sub.2 to C.sub.10 alkylene, substituted cyclic C.sub.2 to C.sub.10 alkylene, cyclic C.sub.2 to C.sub.10 heteroalkylene, substituted cyclic C.sub.2 to C.sub.10 heteroalkylene, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, (monosubstituted)amino, protected (monosubstituted)amino, (disubstituted)amino, carboxamide, protected carboxamide, C.sub.1 to C.sub.4 alkylthio, C.sub.1 to C.sub.4 alkylsulfonyl, methylsulfonylamino, C.sub.1 to C.sub.4 alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl, and substituted phenylsulfonyl;
• R.sup.3 is selected from the group consisting of C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, and substituted phenyl;
• Y may be absent and, if present, is selected from the group consisting of a carboxylic acid, carboxamide, protected carboxamide, an amino resin, a hydroxy resin, methylamine, and N-alkylated methylamine.

A combinatorial library of quinazolinone derivatives comprising quinazolinone derivatives of the structure:

• ##STR43## wherein:
• R.sup.1 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.6 alkyl;
• C.sub.1 to C.sub.6 substituted alkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
• R.sup.2 is selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, cyano, nitro, C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.1 to C.sub.4 alkoxy, C.sub.1 to C.sub.7 acyloxy, C.sub.1 to C.sub.7 acyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.3 to C.sub.7 cycloalkenyl, C.sub.3 to C.sub.7 substituted cycloalkenyl, a heterocyclic ring, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, cyclic C.sub.2 to C.sub.10 alkylene, substituted cyclic C.sub.2 to C.sub.10 alkylene, cyclic C.sub.2 to C.sub.10 heteroalkylene, substituted cyclic C.sub.2 to C.sub.10 heteroalkylene, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, (monosubstituted)amino, protected (monosubstituted) amino, (disubstituted) amino, carboxamide, protected carboxamide, C.sub.1 to C.sub.4 alkylthio, C.sub.1 to C.sub.4 alkylsulfonyl, methylsulfonylamino, C1 to C4 alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl, and substituted phenylsulfonyl
• R.sup.3 is selected from the group consisting of C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, and substituted phenyl;
• R.sup.5 is selected from the group consisting of C.sub.1 to C.sub.6 alkyl;
• C.sub.1 to C.sub.6 substituted alkyl, C.sub.1 to C.sub.4 alkoxy, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, and substituted phenyl;
• Y may be absent and, if present, is selected from the group consisting of a carboxylic acid, carboxamide, protected carboxamide, an amino resin, a hydroxy resin, methylamine, and N-alkylated methylamine.

A combinatorial library of quinazolinone derivatives comprising quinazolinone derivatives of the structure:

• ##STR44## wherein:
• R.sup.1 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.6 alkyl;
• C.sub.1 to C.sub.6 substituted alkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
• R.sup.2 is selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, cyano, nitro, C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.1 to C.sub.4 alkoxy, C.sub.1 to C.sub.7 acyloxy, C.sub.1 to C.sub.7 acyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.3 to C.sub.7 cycloalkenyl, C.sub.3 to C.sub.7 substituted cycloalkenyl, a heterocyclic ring, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, cyclic C.sub.2 to C.sub.10 alkylene, substituted cyclic C.sub.2 to C.sub.10 alkylene, cyclic C.sub.2 to C.sub.10 heteroalkylene, substituted cyclic C.sub.2 to C.sub.10 heteroalkylene, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, (monosubstituted)amino, protected (monosubstituted) amino, (disubstituted) amino, carboxamide, protected carboxamide, C.sub.1 to C.sub.4 alkylthio, C.sub.1 to C.sub.4 alkylsulfonyl, methylsulfonylamino, C1 to C4 alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl, and substituted phenylsulfonyl;
• R.sup.6 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.6 alkyl;
• C.sub.1 to C.sub.6 substituted alkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, carboxylic acid, carboxamide, and protected carboxamide;
• Y may be absent and, if present, is selected from the group consisting of a carboxylic acid, carboxamide, protected carboxamide, an amino resin, a hydroxy resin, methylamine, and N-alkylated methylamine.

A combinatorial library of quinazolinone derivatives comprising quinazolinone derivatives of the structure:

• ##STR45## wherein:
• R.sup.1 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.6 alkyl;
• C.sub.1 to C.sub.6 substituted alkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
• R.sup.2 is selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, cyano, nitro, C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.1 to C.sub.4 alkoxy, C.sub.1 to C.sub.7 acyloxy, C.sub.1 to C.sub.7 acyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.3 to C.sub.7 cycloalkenyl, C.sub.3 to C.sub.7 substituted cycloalkenyl, a heterocyclic ring, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, cyclic C.sub.2 to C.sub.10 alkylene, substituted cyclic C.sub.2 to C.sub.10 alkylene, cyclic C.sub.2 to C.sub.10 heteroalkylene, substituted cyclic C.sub.2 to C.sub.10 heteroalkylene, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, (monosubstituted)amino, protected (monosubstituted)amino, (disubstituted)amino, carboxamide, protected carboxamide, C.sub.1 to C.sub.4 alkylthio, C.sub.1 to C.sub.4 alkylsulfonyl, methylsulfonylamino, C1 to C4 alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl, and substituted phenylsulfonyl;
• R.sup.3 is selected from the group consisting of C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, and substituted phenyl;
• Y may be absent and, if present, is selected from the group consisting of a carboxylic acid, carboxamide, protected carboxamide, an amino resin, a hydroxy resin, methylamine, and N-alkylated methylamine;
• Z is a heteroaromatic ring having from two to six carbons and one or two heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen.