Protective molecules against anthrax toxin

Patent metadata

Field	Value
Publication number	US-2016016930-A1
Application number	US-201514801247-A
Country	US
Kind code	A1
Filing date	Jul 16, 2015
Priority date	Jan 16, 2013
Publication date	Jan 21, 2016
Grant date	—

Abstract

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

First claim

1 . A compound of the formula:

or pharmaceutically acceptable salt thereof, wherein
ring A is a substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene or substituted or unsubstituted heteroarylene;
R 100 is 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 6 is hydrogen, halogen, C(X 1 ) 3 , —OC(X 1 ) 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 11A R 12A , —OR 13A , —SR 14A , 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 101 is independently hydrogen, halogen, —C(X 3 ) 3 , —OC(X 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 1C 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;
L 100 is —NHC(═R 7 )— or —N═C(NH 2 )—;
L 101 is —NH—CH(R 10 )— or —N═C(R 10 )—;
R 7 is O, S, or NH;
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, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
X 1 , X 2 and X 3 are independently a halogen; and
z is an integer from 0 to 9.

2 . (canceled)

3 . The compound of claim 2 , wherein ring A is an unsubstituted arylene or unsubstituted heteroarylene.

4 . (canceled)

5 . The compound of claim 3 , wherein ring A is an unsubstituted C 6 arylene or unsubstituted 5 to 6 membered heteroarylene.

6 . The compound of claim 1 , wherein R 100 is substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted 2 to 8 membered heteroalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted 3 to 8 membered heterocycloalkyl, substituted or unsubstituted C 6 -C 10 aryl or substituted or unsubstituted 5 to 10 membered heteroaryl.

7 . The compound of claim 6 , wherein R 100 is substituted or unsubstituted C 6 -C 10 aryl or substituted or unsubstituted 5 to 10 membered heteroaryl.

8 . (canceled)

9 . The compound of claim 6 , wherein R 100 is substituted C 6 aryl or substituted 5 to 6 membered heteroaryl.

10 . The compound of claim 1 , having the formula:

wherein
each R 2 is independently hydrogen, halogen, —CX 3 3 , —OCX 33 , —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 8 is independently hydrogen, 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;
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;
is a single or double bond, wherein if is a single bond than —N C(R 10 )— is —NH—CH(R 10 )— and if is a double bond than —N C(R 10 )— is —N═C(R 10 )—;
each X is independently a halogen; and
z11 and z2 are independently an integer from 0 to 5.

11 . The compound of claim 1 , having the formula:

wherein
each 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 , —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 8 is independently hydrogen, 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;
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;
is a single or double bond, wherein if is a single bond than —N C(R 10 )— is —NH—CH(R 10 )— and if is a double bond than —N C(R 10 )— is —N═C(R 10 )—;
each X is independently a halogen;
L is —O— or —S—;
z1 is an integer from 0 to 5; and
z3 is an integer from 0 to 3.

12 . The compound of claim 1 having the formula:

wherein
each R 1 , R 2 , R 3 , R 4 , R 5 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 8 and R 9 is independently hydrogen, 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 unsubs

Assignees

• Univ California

Inventors

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

Classifications

• A61P31/12

  Antivirals · CPC title

• C07C337/08

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

• C07C335/26

  Y being a hydrogen or a carbon atom, e.g. benzoylthioureas · CPC title

• C07C281/18

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

• C07D333/28 Primary

  Halogen atoms · CPC title