A method of making a compound of formula I or a stereoisomer or mixture of stereoisomers thereof: the method comprising contacting a compound of formula II: with a compound of formula III: under reaction conditions sufficient to produce a compound of formula I; wherein Z is O, NR 1, or S; R 1 is selected from the group consisting of hydrogen and alkyl; R 2 is selected from the group consisting of hydrogen and alkyl which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl, and heteroaryl; R 3 and R 4 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halo, hydroxy, cyano, -S n -N(R 8)-R 8, -NR 8 C NR 8 R 8, and -X 1 R 8; where X 1 is oxygen, -S n -, or -NR 9 -; n is 0, 1, or 2; each R 8 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl provided that when X 1 is -SO- or -SO 2 -, then R 8 is not hydrogen; and R 9 is selected from the group consisting of hydrogen, alkyl, and aryl; or R 3 and R 4 together with the carbon atoms pendent thereto, form a cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; R 5 and R 6 are independently selected from the group consisting of hydrogen, halo, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl and -X 2 R 10; where X 2 is oxygen, -S n -, or -NR 13 -; n is 0, 1, or 2; R 10 is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; and R 13 is selected from the group consisting of hydrogen, alkyl, and aryl; or when X 2 is -NR 13 -, then R 10 and R 13, together with the nitrogen atom to which they are bound, can be joined to form a heterocyclyl or substituted heterocyclyl group; and each R 11 is independently selected from alkyl, benzyl and aryl, or two R 11 together with the nitrogen atom to which they are attached form a 4-8 membered heterocyclyl or a heteroaryl. Z is O, NR 1, or S; R 1 is selected from the group consisting of hydrogen and alkyl; R 2 is selected from the group consisting of hydrogen and alkyl which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl, and heteroaryl; R 3 and R 4 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halo, hydroxy, cyano, -S n -N(R 8)-R 8, -NR 8 C NR 8 R 8, and -X 1 R 8; where X 1 is oxygen, -S n -, or -NR 9 -; n is 0, 1, or 2; each R 8 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl provided that when X 1 is -SO- or -SO 2 -, then R 8 is not hydrogen; and R 9 is selected from the group consisting of hydrogen, alkyl, and aryl; or R 3 and R 4 together with the carbon atoms pendent thereto, form a cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; n is 0, 1, or 2; each R 8 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl provided that when X 1 is -SO- or -SO 2 -, then R 8 is not hydrogen; and R 9 is selected from the group consisting of hydrogen, alkyl, and aryl; R 5 and R 6 are independently selected from the group consisting of hydrogen, halo, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl and -X 2 R 10; where X 2 is oxygen, -S n -, or -NR 13 -; n is 0, 1, or 2; R 10 is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; and R 13 is selected from the group consisting of hydrogen, alkyl, and aryl; or when X 2 is -NR 13 -, then R 10 and R 13, together with the nitrogen atom to which they are bound, can be joined to form a heterocyclyl or substituted heterocyclyl group; and n is 0, 1, or 2; R 10 is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; and R 13 is selected from the group consisting of hydrogen, alkyl, and aryl; or when X 2 is -NR 13 -, then R 10 and R 13, together with the nitrogen atom to which they are bound, can be joined to form a heterocyclyl or substituted heterocyclyl group; and each R 11 is independently selected from alkyl, benzyl and aryl, or two R 11 together with the nitrogen atom to which they are attached form a 4-8 membered heterocyclyl or a heteroaryl.