2-aminobenzoxazole derivatives and combinatorial libraries thereof

A single compound of the structure:

• wherein R1 and R4, and one of R2 and R3, are independently selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, cyano, C1 to C12 alkyl, C2 to C12 alkenyl, C2 to C12 alkynyl, C1 to C12 substituted alkyl, C2 to C12 substituted alkenyl, C2 to C12 substituted alkynyl, C1 to C12 alkoxy, C1 to C12 substituted alkoxy, C1 to C12 acyloxy, C1 to C12 acyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, heterocyclic ring, substituted heterocyclic ring, C7 to C18 phenylalkyl, C7 to C18 substituted phenylalkyl, C1 to C12 heterocycloalkyl, C1 to C12 substituted heterocycloalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, cyclic C2 to C7 alkylene, substituted cyclic C2 to C7 alkylene, cyclic C2 to C7 heteroalkylene, substituted cyclic C2 to C7 heteroalkylene, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, protected amino, protected (monosubstituted)amino, (disubstituted)amino, C1 to C10 alkyl protected amino, C1 to C10 alkyl protected (monosubstituted)amino, C1 to C10 alkyl (disubstituted)amino, C1 to C10 substituted alkylamino, C1 to C10 substituted alkyl protected (monosubstituted)amino, C1 to C10 substituted alkyl(disubstituted)amino, carboxamide, C1 to C10 alkylthio, C1 to C10 substituted alkylthio, C1 to C10 alkylsulfonyl, C1 to C10 substituted alkylsulfonyl, C1 to C10 alkylsulfoxide, C1 to C10 substituted alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulf oxide, substituted phenylsulfoxide, phenylsulfonyl, substituted phenylsulfonyl and the group consisting of (i) the formula —C(O)NR11R12, (ii) the formula —SR11, (iii) the formula —OR11 and (iv) the formula —C(O)OR11, wherein R11 and R12 are, independently, selected from the group consisting of a hydrogen atom, C1 to C12 alkyl, C1 to C12 substituted alkyl, C2 to C12 alkenyl, C2 to C12 substituted alkenyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C7 to C18 phenylalkyl, C7 to C18 substituted phenylalkyl, C1 to C12 heterocycloalkyl, C1 to C12 substituted heterocycloalkyl, heteroaryl, substituted heteroaryl, heterocycle and substituted heterocycle;
• the other of R2 and R3 is selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, carboxy, thio, C1 to C12 alkyl, C2 to C12 alkenyl, C2 to C12 alkynyl, C1 to C12 substituted alkyl, C2 to C12 substituted alkenyl, C2 to C12 substituted alkynyl, C1 to C12 alkoxy, C1 to C12 substituted alkoxy, C1 to C12 acyloxy, C1 to C12 acyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, heterocyclic ring, substituted heterocyclic ring, C7 to C18 phenylalkyl, C7 to C18 substituted phenylalkyl, C1 to C12 heterocycloalkyl, C1 to C12 substituted heterocycloalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, cyclic C2 to C7 alkylene, substituted cyclic C2 to C7 alkylene, cyclic C2 to C7 heteroalkylene, substituted cyclic C2 to C7 heteroalkylene, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, protected amino, protected (monosubstituted) amino, (disubstituted) amino, C1 to C10 alkyl protected amino, C1 to C10 alkyl protected (monosubstituted)amino, C1 to C10 alkyl(disubstituted)amino, C1 to C10 substituted alkyl protected amino, C1 to C10 substituted alkyl protected (monosubstituted)amino, C1 to C10 substituted alkyl(disubstituted)amino, carboxamide, C1 to C10 alkylthio, C1 to C10 substituted alkylthio, C1 to C10 alkylsulfonyl, C1 to C10 substituted alkylsulfonyl, C1 to C10 alkylsulfoxide, C1 to C10 substituted alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulf oxide, substituted phenylsulfoxide, phenylsulfonyl, substituted phenylsulfonyl and the group consisting of (i) the formula —C(O)NR11R12, (ii) the formula —SR11, (iii) the formula —OR11, (iv) the formula —C(O)OR11 and (v) the formula S(O)2NR11R12, wherein R11 and R12 are, independently, selected from the group consisting of a hydrogen atom, C1 to C12 alkyl, C1 to C12 substituted alkyl, C2 to C12 alkenyl, C2 to C12 substituted alkenyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C7 to C18 phenylalkyl, C7 to C18 substituted phenylalkyl, C1 to C12 heterocycloalkyl, C1 to C12 substituted heterocycloalkyl, heteroaryl, substituted heteroaryl, heterocycle and substituted heterocycle;
• Z is the structure A:
• or the structure B:
• or the structure C:
• wherein, in structure A, Q is the formula ((CH2)nNH)m, where m is 0 or 1, n is 1 to 6 and the alkylene portion of Q is directly attached to the depicted nitrogen atom in structure A;
• and the dotted line between R6 and R7 indicates that R6 and R7 are optionally directly attached;
• wherein, in structure B, the depicted cyclic portion is an unsubstituted or substituted heterocycle that is fully saturated, contains 4 to 7 ring atoms, 1 to 2 nitrogen rings atoms and 0 to 1 other heteroatoms selected from oxygen and sulfur;
• wherein, in structure C, K is absent or present and, if present, is a C1 to C12 alkylene;
• R5 is selected from the group consisting of C1 to C10 alkylene, C2 to C10 alkenylene, C2 to C10 alkynylene, C1 to C10 substituted alkylene, C2 to C10 substituted alkenylene, C2 to C10 substituted alkynylene, substituted epimino, C1 to C5 substituted alkylene epimino, thio, C1 to C10 alkylene thio, C1 to C10 substituted alkylene thio, sulfonyl, C1 to C10 alkylene sulfonyl, C1 to C10 substituted alkylene sulfonyl, sulfinyl, C1 to C10 alkylene sulfinyl, C1 to C10 substituted alkylene sulfinyl, oxy, C1 to C10 alkylene oxy, C1 to C10 substituted alkylene oxy, C1 to C10 alkylene dioxy, C1 to C10 substituted alkylene dioxy, C1 to C10 alkylene trioxy and C1 to C10 substituted alkylene trioxy;
• X is absent or present and, if present, is selected from the group consisting of carbonyl, thiocarbonyl, thioester, sulfonyl and sulfinyl;
• where R6 and R7 are not directly attached to each other, they are independently selected from the group consisting of a hydrogen atom, C1 to C12 alkyl, C2 to C12 alkenyl, C2 to C12 alkynyl, C1 to C12 substituted alkyl, C2 to C12 substituted alkenyl, C2 to C12 substituted alkynyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, heterocyclic ring, substituted heterocyclic ring, C7 to C18 phenylalkyl, C7 to C18 substituted phenylalkyl, C1 to C12 heterocycloalkyl, C1 to C12 substituted heterocycloalkyl, cyclic C2 to C7 alkylene, substituted cyclic C2 to C7 alkylene, cyclic C2 to C7 heteroalkylene, substituted cyclic C2 to C7 heteroalkylene, hydroxymethyl and protected hydroxymethyl;
• or
• where R6 and R7 are directly attached to each other are, collectively selected from the group consisting of C1 to C5 alkylene, C2 to C5 alkenylene, C2 to C5 alkynylene, C1 to C5 substituted alkylene, C2 to C5 substituted alkenylene, C2 to C5 substituted alkynylene, substituted epimino, C1 to C5 substituted alkylene epimino, thio, C1 to C5 alkylene thio, C1 to C5 substituted alkylene thio, sulfonyl, C1 to C5 alkylene sulfonyl, C1 to C5 substituted alkylene sulfonyl, sulfinyl, C1 to C5 alkylene sulfinyl, C1 to C5 substituted alkylene sulfinyl, oxy, C1 to C5 alkylene oxy, C1 to C5 substituted alkylene oxy, C1 to C5 alkylene dioxy, C1 to C5 substituted alkylene dioxy, C1 to C5 alkylene trioxy and C1 to C5 substituted alkylene trioxy;
• and
• X is absent or present and, if present, is selected from the group consisting of carbonyl, thiocarbonyl, thioester, sulfonyl and sulfinyl;
• and
• R8 and, if present, R9 are independently selected from the group consisting of a hydrogen atom, C1 to C12 alkyl, C2 to C12 alkenyl, C2 to C12 alkynyl, C1 to C12 substituted alkyl, C2 to C12 substituted alkenyl, C2 t o C12 substituted alkynyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, heterocyclic ring, substituted heterocyclic ring, C7 to C8 phenylalkyl, C7 to C18 substituted phenylalkyl, C1 to C12 heterocycloalkyl, C1 to C12 substituted heterocycloalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, cyclic C2 to C7 alkylene, substituted cyclic C2 to C7 alkylene, cyclic C2 to C7 heteroalkylene, substituted cyclic C2 to C7 heteroalkylene, protected hydroxymethyl, protected amino, (monosubstituted) amino, protected (monosubstituted)amino, (disubstituted)amino, C1 to C10 alkylamino, C1 to C10 alkyl protected amino, C1 to C10 alkyl (monosubstituted)amino, C1 to C10 alkyl, protected (monosubstituted)amino, C1 to C10 alkyl (disubstituted) amino, C1 to C10 substituted alkylamino, C1 to C10 substituted alkyl protected amino, C1 to C10 substituted alkyl (monosubstituted)amino, C1 to C10 substituted alkyl protected (monosubstituted)amino, C1 to C10 substituted alkyl (disubstituted) amino, carboxamide, protected carboxamide, and the group consisting of (i) the formula —C(O)NR11R12, (ii) the formula —C(O)R11, (iii) the formula —NR11R12, (iv) the formula —C(O)OR11, wherein R11 and R12 are, independently, selected from the group consisting of a hydrogen atom, C1 to C12 alkyl, C1 to C12 substituted alkyl, C2 to C12 alkenyl, C2 to C12 substituted alkenyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C7 to C18 phenylalkyl, C7 to C18 substituted phenylalkyl, C1 to C12 heterocycloalkyl, C1 to C12 substituted heterocycloalkyl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, C1 to C12 acyl, C1 to C12 substituted acyl, phenylsulfonyl, substituted phenylsulfonyl, C1 to C10 alkylsulfonyl, C1 to C10 substituted alkylsulfonyl, C1 to C12 alkylaminocarbonyl, C1 to C12 substituted alkylaminocarbonyl, phenylaminocarbonyl, and substituted phenylaminocarbonyl;
• or
• R8 and R9, together with the adjoining nitrogen depicted in structure B are, collectively, selected from the group consisting of heterocycle and substituted heterocycle;
• provided that, if X is carbonyl, R8 is not alkoxy;
• provided that X can only be absent where R6 and R7 are not directly attached to each other;
• and
• provided that, if R8 is substituted cyclic C2 to C7, heteroalkylene, said substitution is selected from the group consisting of hydroxy, protected hydroxy, carboxy, protected carboxy, C1 to C4 acyloxy, formyl, C1 to C12 acyl, C1 to C12 alkyl, C1 to C7 alkoxy, C1 to C10 alkylthio, C1 to C10 alkylsulfoxide, C1 to C10 alkylsulfonyl, halo, amino, protected amino, (monosubstituted)amino, protected (monosubstituted) amino, (disubstituted) amino, hydroxymethyl or a protected hydroxymethyl;
• or
• a salt of said compound.