# US 9,751,831 B2 · Blood brain barrier-penetrating oximes for cholistenerases reactivation

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- Number: US 9,751,831 B2
- Document ID: US9751831B2
- Status: Granted
- Kind: B2
- Application number: 13/994,682
- Filed: 2011-12-16
- Published: 2014-02-20
- Granted: 2017-09-05
- Earliest claimed: 2010-12-16
- Assignees: Human BioMolecular Research Institute
- Applicants: John R. Cashman; Jarosiaw Kalisiak
- Inventors: John R. Cashman; Jarosiaw Kalisiak
- Web page: https://patentgrep.com/patent/US9751831B2

## CPC

- C07C 251/40: to carbon atoms of an unsaturated carbon skeleton
- C07C 257/12: having carbon atoms of amidino groups bound to hydrogen atoms
- C07C 257/14: having carbon atoms of amidino groups bound to acyclic carbon atoms
- C07C 257/18: having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
- C07C 279/12: being further substituted by nitrogen atoms not being part of nitro or nitroso groups
- C07D 233/24: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- C07D 239/06: having one double bond between ring members or between a ring member and a non-ring member
- C07D 249/04: 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention describes pharmaceutical agents capable of crossing the blood brain barrier to protect against organophosphate pesticides and nerve agents or other electrophiles by reactivating inhibited cholinesterase (i.e., acetylcholinesterase and butyrylcholinesterase) and other proteins in the peripheral and central nervous system.

## Claims

### Claim 1

A compound of Formula V, VI or VII:
or a pharmaceutically acceptable salt thereof, wherein
R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylidenyl, alkenylidenyl, alkoxy, halo, haloalkyl, azidoalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkoxycarbonyl, alkylimino, alkylamino, acylamino, trifluoromethylalkyl, trifluoromethoxyalkyl, carboxyalkyl, ketoalkyl, thioalkyl, alkylsulfinyl, alkylsulfonyl, amidinoalkyl, guanidynoalkyl, oximoalkyl, NRxRy and COORy wherein each Rx and Ry are independently hydrogen, alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxy.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient or carrier.

### Claim 3 (depends on 1)

The compound of claim 1 wherein R is C1-C6 alkyl.

### Claim 4 (depends on 3)

The compound of claim 3 wherein R is selected from the group consisting of methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, pentyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl and 3,3-dimethyl-2-butyl.

### Claim 5 (depends on 4)

The compound of claim 4 wherein the compound has the structure of Formula VI.

### Claim 6 (depends on 5)

The compound of claim 5 wherein the compound has the structure of
or a pharmaceutical acceptable salt thereof.