IP Library Patent Application 17247834
Patent Application
App. No. 17/247,834

BORON-CONTAINING SMALL MOLECULES

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Quick Facts
Patent No.
US None
App. No.
17/247,834
Abstract

Compounds, pharmaceutical formulations, and methods of treating bacterial infections are disclosed.

Claims (67)

1 . A compound, or a salt or a hydrate or a solvate thereof, having a structure which is:

wherein

W is H or a bond to X;

X is

wherein

R a and R b are each independently selected from the group consisting of R 15 , —OR 15 , —NR 15 R 16 , —SR 15 , —S(O)R 15 , —S(O) 2 R 15 , —S(O) 2 NR 15 R 16 , —C(O)R 15 , —C(O)OR 15 , and —C(O)NR 15 R 16

wherein R 15 and R 16 are each independently selected from the group consisting of H, halogen, cyano, nitro, —OR 17 , —NR 17 R 18 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl

wherein R 17 and R 18 are each independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl

and wherein R 15 and R 16 , and/or R 17 and R 18 , along with the nitrogen to which they are connected, are optionally joined to form a substituted or unsubstituted 4- to 8-membered ring

with the proviso that R a and R b are not both H;

or X is

wherein

R c is —OR 15 , —NR 15 R 16 , —SR 15 , —S(O)R 15 , —S(O) 2 R 15 , —S(O) 2 NR 15 R 16 , —C(O)R 15 , —C(O)OR 15 , and —C(O)NR 15 R 16

wherein R 15 and R 16 are each independently selected from the group consisting of H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl

and wherein R 15 and R 16 , along with the nitrogen to which they are connected, are optionally joined to form a substituted or unsubstituted 4- to 8-membered ring

or X is

wherein

R d and R e are each independently selected from the group consisting of H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, —OR 15 , —NR 15 R 16 , —SR 15 , —S(O)R 15 , —S(O) 2 R 15 , —S(O) 2 NR 15 R 16 , —C(O)R 15 , —C(O)OR 15 , and —C(O)NR 15 R 16

wherein R 15 and R 16 are each independently selected from the group consisting of H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl

and wherein R d and R e , along with the atom to which they are connected, are optionally joined to form a substituted or unsubstituted 3- to 8-membered ring

and wherein R 15 and R 16 , along with the nitrogen to which they are connected, are optionally joined to form a substituted or unsubstituted 4- to 8-membered ring with the proviso that R d and R e are not both H

wherein X optionally comprises an attachment point to W;

Y is selected from the group consisting of a bond, —O—, —S—, —NH—, substituted or unsubstituted alkylene, and substituted or unsubstituted heteroalkylene; and

Z is a substituted or unsubstituted heterocyclic ring or ring system containing at least one endocyclic boron.

2 . The compound of claim 1 , or a salt or a hydrate or a solvate thereof, wherein said X is

wherein

R 15 is selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

3 . The compound of claim 1 , or a salt or a hydrate or a solvate thereof, wherein said X is

wherein

R 15 and R 16 are each independently selected from the group consisting of H, —OR 17 , —NR 17 R 18 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl

wherein R 17 and R 18 are each independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl

and wherein R 15 and R 16 , and/or R 17 and R 18 , along with the nitrogen to which they are connected, are optionally joined to form a substituted or unsubstituted 4- to 8-membered ring.

4 . The compound of claim 1 , or a salt or a hydrate or a solvate thereof, wherein said X is

wherein

R c is selected from the group consisting of H, substituted or unsubstituted alkyl, and —OR 15

wherein R 15 is H or substituted or unsubstituted alkyl.

5 . The compound of claim 1 , or a salt or a hydrate or a solvate thereof, wherein said X is

wherein

R d is selected from the group consisting of halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, —OR 15 , —SR 15 , —S(O)R 15 , —NR 15 R 16 , —C(O)R 15 , —CH 2 C(O)OR 15 , and —CH 2 C(O)NR 15 R 16

wherein R 15 and R 16 are each independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl

and wherein R 15 and R 16 , along with the nitrogen to which they are connected, are optionally joined to form a substituted or unsubstituted 4- to 8-membered ring.

6 . The compound of claim 5 , or a salt or a hydrate or a solvate thereof, wherein R d comprises said attachment point to W.

7 . The compound of claim 1 , or a salt or a hydrate or a solvate thereof, wherein said Y is *—OCH 2 — or *—SCH 2 — or *—NHCH 2 — or *—CH 2 NH— or *—C(O)NH—, wherein * represents the attachment point to said Z.

8 . The compound of claim 1 , or a salt or a hydrate or a solvate thereof, wherein said Z is selected from the group consisting of substituted or unsubstituted benzoxaborole, substituted or unsubstituted pyridinyloxaborole, substituted or unsubstituted benzoxaborininol, substituted or unsubstituted benzoxazaborininol, substituted or unsubstituted benzodiazaborininol, and substituted or unsubstituted oxaborole.

9 . The compound of claim 8 , or a salt or a hydrate or a solvate thereof, wherein said Z is

wherein

R 3 , R 3a , R 4 , R 5 , and R 7 are each independently selected from the group consisting of R 10 , —OR 10 , —NR 10 R 11 , —SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —C(O)R 10 , —C(O)OR 10 , and —C(O)NR 10 R 11

wherein

R 10 and R 11 are each independently selected from the group consisting of H, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

10 . The compound of claim 9 , or a salt or a hydrate or a solvate thereof, wherein said Z is

wherein

R 4 , R 5 , and R 7 are each independently selected from the group consisting of R 10 , —OR 10 , —NR 10 R 11 ,

wherein

R 10 and R 11 are each independently selected from the group consisting of H, halogen, cyano, nitro, substituted or unsubstituted alkyl, and substituted or unsubstituted heteroalkyl.

11 . The compound of claim 10 , or a salt or a hydrate or a solvate thereof, wherein said Z is

12 . A combination comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, together with at least one other therapeutically active agent.

13 . The combination of claim 12 , or a pharmaceutically acceptable salt or a hydrate or a solvate thereof, wherein the other therapeutically active agent is an anti-bacterial agent.

14 . A pharmaceutical formulation comprising:

a) the compound of claim 1 , or a pharmaceutically acceptable salt or a hydrate or a solvate thereof, and

b) a pharmaceutically acceptable excipient.

15 . A method of inhibiting protein synthesis in a bacteria, the method comprising contacting the bacteria with the compound of claim 1 , or a pharmaceutically acceptable salt or a hydrate or a solvate thereof, thereby inhibiting protein synthesis in the bacteria.

16 . A method of inhibiting the growth of and/or killing a bacteria, the method comprising contacting the bacteria with the compound of claim 1 , or a pharmaceutically acceptable salt or a hydrate or a solvate thereof, thereby inhibiting the growth of and/or killing the bacteria.

17 . The method of claim 15 , wherein the bacteria is Gram-positive.

18 . The method of claim 17 , wherein the bacteria is selected from the group consisting of Staphylococcus aureus, Streptococcus pneumoniae , methicillin-resistant Staphylococcus aureus, Wolbachia pipientis , and bacteria of the Wolbachia genus.

19 . A method of treating a disease in an animal, the method comprising administering to the animal a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt or a hydrate or a solvate thereof, thereby treating the disease.

20 . The method of claim 19 , wherein the disease is associated with a Gram-positive bacteria.

21 . The method of claim 19 , wherein the disease is selected from the group consisting of pneumonia, hospital-acquired pneumonia, hospital-associated pneumonia, community-acquired pneumonia, acute bacterial skin and skin-structure infection (ABSSSI), bacteremia, endocarditis, osteomyelitis, gastroenteritis, toxic shock syndrome, meningitis, septic arthritis, urinary tract infection, skin and skin-structure infection, strep throat, necrotizing fasciitis, otitis media, sinusitis, actinomycosis, diptheria, anthrax, food poisoning, botulism, tetanus, gas gangrene, diarrhea, tuberculosis, leprosy, candidiasis, aspergillosis, coccidioidomycosis, cryptococcosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, zygomycosis, phaeohyphomycosis, rhinosporidiosis, enterobiasis, filariasis, lymphatic filariasis, bancroftian filariasis, subcutaneous filariasis, serious cavity filariasis, elephantiasis, elephantiasis tropica, lymphadenitis, lymphangitis, lymphedema, and onchocerciasis.

Assignments (3)
CHANGE OF NAME Recorded Mar 31, 2025
From: THE BILL & MELINDA GATES FOUNDATION
To: GATES FOUNDATION
Reel/Frame 070690/0764 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 9, 2021
From: LI, XIANFENG; LUNDE, CHRISTOPHER S; JACOBS, ROBERT T; ZHOU, YASHEEN
To: ANACOR PHARMACEUTICALS, INC.
Reel/Frame 056809/0332 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 9, 2021
From: ANACOR PHARMACEUTICALS, INC.
To: BILL & MELINDA GATES FOUNDATION
Reel/Frame 056809/0364 →