Protective molecules against anthrax toxin
Disclosed herein inter alia are compositions and methods useful in the treatment of infectious diseases and exposure to toxins.
1. A method of inhibiting anthrax caused by exposure to Bacillus anthracis in a subject in need thereof, said method comprising administering an effective amount of a compound, or pharmaceutically acceptable salt thereof, to the subject, wherein the compound has the formula:
wherein
R 1 is independently hydrogen, halogen, —CX 3 3 , —OCX 3 3 , —CN, —C(O)OH, —CONH 2 , —NO 2 , —SO 2 Cl, —SO 2 NH 2 , —NHNH 2 , —NHSO 2 CH 3 , —N 3 , —NR 11C R 12C , —OR 13C , —SR 14C , substituted alkyl, substituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 2 is independently hydrogen, halogen, —CX 3 3 , —OCX 3 3 , —CN, —C(O)OH, —CONH 2 , —NO 2 , —SO 2 Cl, —SO 2 NH 2 , —NHNH 2 , —NR 11C R 12C , —OR 13C , —SR 14C , substituted or unsubstituted alkyl, unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 3 is independently hydrogen, halogen, —CX 3 3 , —OCX 3 3 , —CN, —C(O)OH, —CONH 2 , —NO 2 , —SO 2 Cl, —SO 2 NH 2 , —NHNH 2 , —NHSO 2 CH 3 , —N 3 , —NR 11C R 12C , —OR 13C , —SR 14C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
each R 4 is independently hydrogen, halogen, —CX 3 3 , —OCX 3 3 , —CN, —C(O)OH, —CONH 2 , —NO 2 , —SO 2 Cl, —SO 2 NH 2 , —NHNH 2 , —NHSO 2 CH 3 , —N 3 , —NR 11C R 12C , —OR 13C , —SR 14C , substituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 5 is independently hydrogen, —Cl, —Br, —I, —OCX 3 3 , —CN, —C(O)OH, —CONH 2 , —NO 2 , —SO 2 Cl, —SO 2 NH 2 , —NHNH 2 , —NHSO 2 CH 3 , —N 3 , —NR 11C R 12C , —OR 13C , —SR 14C , unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
wherein (i) at least one of R 1 , R 2 , R 3 , R 4 , or R 5 of Formula IV is not hydrogen; and (ii) at least one of R 2 , R 3 , or R 4 of Formula V is not hydrogen;
R 6 is hydrogen or unsubstituted alkyl;
R 7 is O, S, or NH;
each R 8 is independently halogen, —CX 3 , —OCX 3 , —CN, —C(O)OH, —CONH 2 , —NO 2 , —SO 2 Cl, —SO 2 NH 2 , —NHNH 2 , —NHSO 2 CH 3 , —N 3 , —NR 11 R 12 , —OR 13 , —SR 14 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 9 is hydrogen;
each R 11 , R 12 , R 13 , and R 14 is independently a hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 10 is hydrogen, halogen, —C(X 2 ) 3 , —OC(X 2 ) 3 , —CN, —C(O)OH, —CONH 2 , —NO 2 , —SO 2 Cl, —SO 2 NH 2 , —NHNH 2 , —NHSO 2 CH 3 , —N 3 , —NR 11B R 12B , —OR 13B , —SR 14B , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 11A , R 12A , R 13A , R 14A , R 11B , R 12B , R 13B , R 14B , R 11C , R 12C , R 13C , and R 14C are independently a hydrogen, substituted or unsubstituted alkyl, unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
L 1 is —S—;
each X is independently a halogen;
X 1 , X 2 and X 3 are independently a halogen; and
wherein the compound is not any of
2. The method of claim 1 , wherein;
R 1 and R 4 are independently hydrogen, halogen, —OR 13C , substituted alkyl, substituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 2 is independently hydrogen, halogen, —CX 3 3 , —CN, —NHSO 2 CH 3 , —N 3 , —OR 13C , substituted or unsubstituted alkyl, unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 3 and R 5 are independently hydrogen, halogen, —CX 3 3 , —OR 13C , unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
each R 8 is independently substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 10 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl; and
each R 13C is independently a hydrogen or a substituted or unsubstituted alkyl.
3. The compound, of claim 1 , wherein;
R 1 is independently hydrogen, halogen, or —OR 13C ;
R 2 is independently hydrogen, halogen, —CX 3 3 , —CN, —N 3 , —OR 13C , or unsubstituted alkyl;
R 3 is independently hydrogen, halogen, —CX 3 3 , —OR 13C , or unsubstituted alkyl;
R 4 is independently hydrogen, halogen, —OR 13C , or unsubstituted alkyl;
R 5 is independently hydrogen, halogen, —OR 13C , or unsubstituted alkyl;
R 6 is independently hydrogen or unsubstituted alkyl;
each R 8 is independently an unsubstituted alkyl;
R 9 is independently hydrogen;
R 10 is independently hydrogen or unsubstituted alkyl;
each R 13C is independently an unsubstituted alkyl; and
X 3 is —F.
4. The method of claim 1 , wherein the compound is:
5. The method of claim 1 , wherein the compound is co-administered with an antibiotic.
6. The method of claim 1 , wherein the compound is co-administered with an doxycycline and/or ciprofloxacin.
7. The method of claim 4 , wherein the compound is co-administered with an antibiotic.
8. The method of claim 4 , wherein the compound is co-administered with an doxycycline and/or ciprofloxacin.
9. The method of claim 1 , wherein R 2 is independently halogen, —CX 3 3 , —OCX 3 3 , —CN, —C(O)OH, —CONH 2 , —NO 2 , —SO 2 Cl, —SO 2 NH 2 , —NHNH 2 , —NR 11C R 12C , —OR 13C , —SR 14C , substituted or unsubstituted alkyl, unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.
10. The method of claim 1 , wherein R 2 is independently halogen, —CX 3 3 , —CN, —NHSO 2 CH 3 , —N 3 , —OR 13C , substituted or unsubstituted alkyl, unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.
11. The method of claim 1 , wherein R 2 is independently halogen, —CX 3 3 , —CN, —N 3 , —OR 13C , or unsubstituted alkyl.