Protective molecules against anthrax toxin

Patent metadata

Field	Value
Publication number	US-10730848-B2
Application number	US-201514801247-A
Country	US
Kind code	B2
Filing date	Jul 16, 2015
Priority date	Jan 16, 2013
Publication date	Aug 4, 2020
Grant date	Aug 4, 2020

Abstract

Disclosed herein inter alia are compositions and methods useful in the treatment of infectious diseases and exposure to toxins.

First claim

What is claimed is:

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 ,

Assignees

• Univ California

Inventors

• Gillespie Eugene
• Damoiseaux Robert
• Ho Chi-Lee Charlie
• Chamberlain Brian T
• Jung Michael E
• Bradley Kenneth A

Classifications

• C07C281/18

  the other nitrogen atom being further doubly-bound to a carbon atom, e.g. guanylhydrazones · CPC title

• C07C337/08

  the other nitrogen atom being further doubly-bound to a carbon atom, e.g. thiosemicarbazones · CPC title

• C07D231/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07C281/14

  the carbon atom being further bound to a carbon atom of a six-membered aromatic ring · CPC title

• C07C243/22

  having nitrogen atoms of hydrazine groups bound to carbon atoms of six-membered aromatic rings · CPC title