Benzofuran-4,5-diones as selective peptide deformylase inhibitors
View Patent ↗The instant invention provides novel benzofuran-4,5-diones and pharmaceutical compositions thereof useful for inhibiting PDF and for treating proliferative and infectious diseases. Compounds may be selective for eukaryotic (e.g., human) PDF or prokaryotic PDF.
1. A compound of the formula:
wherein:
R 1 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR a ; —C(═O)R a ; —CO 2 R a ; —CN; —SCN; —SR a ; —SOR a ; —SO 2 R a ; —NO 2 ; —N 3 ; —N(R a ) 2 ; —NR a C(═O)R a ; —NR a C(═O)N(R a ) 2 ; —OC(═O)OR a ; —OC(═O)R a ; —OC(═O)N(R a ) 2 ; —NR a C(═O)OR a ; or —C(R a ) 3 ; wherein each occurrence of R a is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
R 2 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR b ; —C(═O)R b ; —CO 2 R b ; —CN; —SCN; —SR b ; —SOR b ; —SO 2 R b ; —NO 2 ; —N 3 ; —N(R b ) 2 ; —NR b C(═O)R a ; —NR b C(═O)N(R b ) 2 ; —OC(═O)OR b ; —OC(═O)R b ; —OC(═O)N(R b ) 2 ; —NR b C(═O)OR b ; or —C(R b ) 3 ; wherein each occurrence of R b is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
wherein R 1 and R 2 when taken together form an optionally substituted, saturated or unsaturated aromatic, heteroaromatic, or nonaromatic 3-8 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms selected from the group consisting of N, O, or S;
R 3 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR c ; —C(═O)R c ; —CO 2 R c ; —CN; —SCN; —SR c ; —SOR c ; —SO 2 R c ; —NO 2 ; —N 3 ; —N(R c ) 2 ; —NR c C(═O)R c ; —NR c C(═O)N(R c ) 2 ; —OC(═O)OR c ; —OC(═O)R c ; —OC(═O)N(R c ) 2 ; —NR c C(═O)OR c ; or —C(R c ) 3 ; wherein each occurrence of R c is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety; and
R 4 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR d ; —C(═O)R d ; —CO 2 R d ; —CN; —SCN; —SR d ; —SOR b ; —SO 2 R d ; —NO 2 ; —N 3 ; —N(R d ) 2 ; —NR d C(═O)R d ; —NR d C(═O)N(R d ) 2 ; —OC(═O)OR d ; —OC(═O)R d ; —OC(═O)N(R d ) 2 ; —NR d C(═O)OR d ; or —C(R d ) 3 ; wherein each occurrence of R d is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety, or a pharmaceutically acceptable salt thereof; and
wherein the compound is not of one of the formulae:
2. The compound of claim 1 , wherein at least one occurrence of R 1 and R 2 is hydrogen.
3. The compound of claim 1 , wherein at least one occurrence of R 1 and R 2 is a halogen.
4. The compound of claim 1 , wherein R 1 and R 2 taken together form a fused aryl or heteroaryl.
5. The compound of claim 1 , wherein R 3 is hydrogen or C 1 -C 6 alkyl.
6. The compound of claim 1 , wherein R 4 is acyl.
7. The compound of claim 1 of the formula:
wherein
R 5 is hydrogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR e ; —SR e ; —N(R e ) 2 ; —NR e C(═O)R e ; —NR e C(═O)N(R e ) 2 ; —OC(═O)OR e ; —OC(═O)R e ; —OC(═O)N(R e ) 2 ; —NR e C(═O)OR e ; or —C(R e ) 3 ; wherein each occurrence of R e is independently independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety, or a pharmaceutically acceptable salt thereof.
8. The compound of claim 1 of the formula:
wherein:
m is an integer between 0 and 5, inclusive; and
each occurrence of R f is independently hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR g ; —C(═O)R g ; —CO 2 R g ; —CN; —SCN; —SR g ; —SOR g ; —SO 2 R g ; —NO 2 ; —N 3 ; —N(R g ) 2 ; —NR g C(═O)R g ; —NR g C(═O)N(R g ) 2 ; —OC(═O)OR g ; —OC(═O)R g ; —OC(═O)N(R g ) 2 ; —NR g C(═O)OR g ; or —C(R g ) 3 ; wherein each occurrence of R 9 is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety.
9. The compound of claim 7 , wherein R 5 is one of the formulae:
10. The compound of claim 8 , wherein at least one occurrence of R f is —OR g .
11. The compound of claim 8 of the formula:
12. The compound of claim 1 of one of the formulae:
13. The compound of claim 1 of the formula:
wherein:
p is an integer between 0 and 4, inclusive; and
each occurrence of R h is independently hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR i ; —C(═O)R i ; —CO 2 R i ; —CN; —SCN; —SR i ; —SOR i ; —SO 2 R i ; —NO 2 ; —N 3 ; —N(R i ) 2 ; —NR i C(═O)R i ; —NR i C(═O)N(R i ) 2 ; —OC(═O)OR i ; —OC(═O)R i ; —OC(═O)N(R i ) 2 ; —NR i C(═O)OR i ; or —C(R i ) 3 ; wherein each occurrence of R i is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety.
14. The compound of claim 1 of one of the formulae:
15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula:
wherein:
R 1 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR a ; —C(═O)R a ; —CO 2 R a ; —CN; —SCN; —SR a ; —SOR a ; —SO 2 R a ; —NO 2 ; —N 3 ; —N(R a ) 2 ; —NR a C(═O)R a ; —NR a C(═O)N(R a ) 2 ; —OC(═O)OR a ; —OC(═O)R a ; —OC(═O)N(R a ) 2 ; —NR a C(═O)OR a ; or —C(R a ) 3 ; wherein each occurrence of R a is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
R 2 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR b ; —C(═O)R b ; —CO 2 R b ; —CN; —SCN; —SR b ; —SOR b ; —SO 2 R b ; —NO 2 ; —N 3 ; —N(R b ) 2 ; —NR b C(═O)R a ; —NR b C(═O)N(R b ) 2 ; —OC(═O)OR b ; —OC(═O)R b ; —OC(═O)N(R b ) 2 ; —NR b C(═O)OR b ; or —C(R b ) 3 ; wherein each occurrence of R b is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
wherein R 1 and R 2 when taken together form an optionally substituted, saturated or unsaturated aromatic, heteroaromatic, or nonaromatic 3-8 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms selected from the group consisting of N, O, or S;
R 3 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR c ; —C(═O)R c ; —CO 2 R c ; —CN; —SCN; —SR c ; —SOR c ; —SO 2 R c ; —NO 2 ; —N 3 ; —N(R c ) 2 ; —NR c C(═O)R c ; —NR c C(═O)N(R c ) 2 ; —OC(═O)OR c ; —OC(═O)R c ; —OC(═O)N(R c ) 2 ; —NR c C(═O)OR c ; or —C(R c ) 3 ; wherein each occurrence of R c is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety; and
R 4 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR d ; —C(═O)R d ; —CO 2 R d ; —CN; —SCN; —SR d ; —SOR d ; —SO 2 R d ; —NO 2 ; —N 3 ; —N(R d ) 2 ; —NR d C(═O)R d ; —NR d C(═O)N(R d ) 2 ; —OC(═O)OR d ; —OC(═O)R d ; —OC(═O)N(R d ) 2 ; —NR d C(═O)OR d ; or —C(R d ) 3 ; wherein each occurrence of R d is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
16. The composition of claim 15 , wherein the compound is of one of the formulae:
or a pharmaceutically acceptable salt thereof.
17. A method for inducing apoptosis comprising contacting a cell with a compound of the formula:
wherein:
R 1 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR a ; —C(═O)R a ; —CO 2 R a ; —CN; —SCN; —SR a ; —SOR a ; —SO 2 R a ; —NO 2 ; —N 3 ; —N(R a ) 2 ; —NR a C(═O)R a ; —NR a C(═O)N(R a ) 2 ; —OC(═O)OR a ; —OC(═O)R a ; —OC(═O)N(R a ) 2 ; —NR a C(═O)OR a ; or —C(R a ) 3 ; wherein each occurrence of R a is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
R 2 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR b ; —C(═O)R b ; —CO 2 R b ; —CN; —SCN; —SR b ; —SOR b ; —SO 2 R b ; —NO 2 ; —N 3 ; —N(R b ) 2 ; —NR b C(═O)R a ; —NR b C(═O)N(R b ) 2 ; —OC(═O)OR b ; —OC(═O)R b ; —OC(═O)N(R b ) 2 ; —NR b C(═O)OR b ; or —C(R b ) 3 ; wherein each occurrence of R b is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
wherein R 1 and R 2 when taken together form an optionally substituted, saturated or unsaturated aromatic, heteroaromatic, or nonaromatic 3-8 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms selected from the group consisting of N, O, or S;
R 3 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR c ; —C(═O)R c ; —CO 2 R c ; —CN; —SCN; —SR c ; —SOR c ; —SO 2 R c ; —NO 2 ; —N 3 ; —N(R c ) 2 ; —NR c C(═O)R c ; —NR c C(═O)N(R c ) 2 ; —OC(═O)OR c ; —OC(═O)R c ; —OC(═O)N(R c ) 2 ; —NR c C(═O)OR c ; or —C(R c ) 3 ; wherein each occurrence of R c is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety; and
R 4 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR d ; —C(═O)R d ; —CO 2 R d ; —CN; —SCN; —SR d ; —SOR d ; —SO 2 R d ; —NO 2 ; —N 3 ; —N(R d ) 2 ; —NR d C(═O)R d ; —NR d C(═O)N(R d ) 2 ; —OC(═O)OR d ; —OC(═O)R d ; —OC(═O)N(R d ) 2 ; —NR d C(═O)OR d ; or —C(R d ) 3 ; wherein each occurrence of R d is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety, or a pharmaceutically acceptable salt thereof, in an amount effective to induce apoptosis.
18. A method for treating a proliferative disease comprising administering to a subject in need thereof a therapeutically effective amount of a compound of the formula:
wherein:
R 1 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR a ; —C(═O)R a ; —CO 2 R a ; —CN; —SCN; —SR a ; —SOR a ; —SO 2 R a ; —NO 2 ; —N 3 ; —N(R a ) 2 ; —NR a C(═O)R a ; —NR a C(═O)N(R a ) 2 ; —OC(═O)OR a ; —OC(═O)R a ; —OC(═O)N(R a ) 2 ; —NR a C(═O)OR a ; or —C(R a ) 3 ; wherein each occurrence of R a is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
R 2 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR b ; —C(═O)R b ; —CO 2 R b ; —CN; —SCN; —SR b ; —SOR b ; —SO 2 R b ; —NO 2 ; —N 3 ; —N(R b ) 2 ; —NR b C(═O)R a ; —NR b C(═O)N(R b ) 2 ; —OC(═O)OR b ; —OC(═O)R b ; —OC(═O)N(R b ) 2 ; —NR b C(═O)OR b ; or —C(R b ) 3 ; wherein each occurrence of R b is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
wherein R 1 and R 2 when taken together form an optionally substituted, saturated or unsaturated aromatic, heteroaromatic, or nonaromatic 3-8 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms selected from the group consisting of N, O, or S;
R 3 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR c ; —C(═O)R c ; —CO 2 R c ; —CN; —SCN; —SR c ; —SO c ; —SO 2 R c ; —NO 2 ; —N 3 ; —N(R c ) 2 ; —NR c C(═O)R c ; —NR c C(═O)N(R c ) 2 ; —OC(═O)OR c ; —OC(═O)R c ; —OC(═O)N(R c ) 2 ; —NR c C(═O)OR c ; or —C(R c ) 3 ; wherein each occurrence of R c is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety; and
R 4 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR d ; —C(═O)R d ; —CO 2 R d ; —CN; —SCN; —SR d ; —SOR d ; —SO 2 R d ; —NO 2 ; —N 3 ; —N(R d ) 2 ; —NR d C(═O)R d ; —NR d C(═O)N(R d ) 2 ; —OC(═O)OR d ; —OC(═O)R d ; —OC(═O)N(R d ) 2 ; —NR d C(═O)OR d ; or —C(R d ) 3 ; wherein each occurrence of R d is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety, or a pharmaceutically acceptable salt thereof.
19. A method for treating an infectious bacterial disease comprising contacting a cell with a therapeutically effective amount of a compound of the formula:
wherein:
R 1 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR a ; —C(═O)R a ; —CO 2 R a ; —CN; —SCN; —SR a ; —SOR a ; —SO 2 R a ; —NO 2 ; —N 3 ; —N(R a ) 2 ; —NR a C(═O)R a ; —NR a C(═O)N(R a ) 2 ; —OC(═O)OR a ; —OC(═O)R a ; —OC(═O)N(R a ) 2 ; —NR a C(═O)OR a ; or —C(R a ) 3 ; wherein each occurrence of R a is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
R 2 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR b ; —C(═O)R b ; —CO 2 R b ; —CN; —SCN; —SR b ; —SOR b ; —SO 2 R b ; —NO 2 ; —N 3 ; —N(R b ) 2 ; —NR b C(═O)R a ; —NR b C(═O)N(R b ) 2 ; —OC(═O)OR b ; —OC(═O)R b ; —OC(═O)N(R b ) 2 ; —NR b C(═O)OR b ; or —C(R b ) 3 ; wherein each occurrence of R b is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety;
wherein R 1 and R 2 when taken together form an optionally substituted, saturated or unsaturated aromatic, heteroaromatic, or nonaromatic 3-8 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms selected from the group consisting of N, O, or S;
R 3 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR c ; —C(═O)R c ; —CO 2 R c ; —CN; —SCN; —SR c ; —SOR c ; —SO 2 R c ; —NO 2 ; —N 3 ; —N(R c ) 2 ; —NR c C(═O)R c ; —NR c C(═O)N(R c ) 2 ; —OC(═O)OR c ; —OC(═O)R c ; —OC(═O)N(R c ) 2 ; —NR c C(═O)OR c ; or —C(R c ) 3 ; wherein each occurrence of R c is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety; and
R 4 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR d ; —C(═O)R d ; —CO 2 R d ; —CN; —SCN; —SR d ; —SOR d ; —SO 2 R d ; —NO 2 ; —N 3 ; —N(R d ) 2 ; —NR d C(═O)R d ; —NR d C(═O)N(R d ) 2 ; —OC(═O)OR d ; —OC(═O)R d ; —OC(═O)N(R d ) 2 ; —NR d C(═O)OR d ; or —C(R d ) 3 ; wherein each occurrence of R d is independently hydrogen; halogen; a protecting group; an optionally substituted aliphatic or heteroaliphatic moiety; an acyl moiety; or an optionally substituted aryl or heteroaryl moiety, or a pharmaceutically acceptable salt thereof, to treat the infectious disease.