Antiparasitic Compositions and Methods Utilizing Substituted 5,5,7,7-Tetramethyl- 4,5,6,7-Tetrahydrothieno[2,3-C]Pyridine Derivatives

Patent metadata

Field	Value
Publication number	US-2016362420-A1
Application number	US-201615179865-A
Country	US
Kind code	A1
Filing date	Jun 10, 2016
Priority date	Jun 10, 2015
Publication date	Dec 15, 2016
Grant date	—

Abstract

The present disclosure relates generally to systems, methods, and compounds for therapeutic use against parasitic infections. More particularly, the disclosure relates to anti-parasitic compounds, and methods for making and for using the anti-parasitic compounds, where the anti-parasitic compounds have the general formula:

where X, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are defined more fully below.

First claim

What is claimed is:

1 . An antiparasitic compound having a general formula of Formula I:

wherein X is O or N;
R 1 is a C2 to C4 alky or C2 to C4 cycloalkyl;
R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from hydrogen (H), chlorine (Cl), bromine (Br), fluorine (F), CF 3 , SF 5 , substituted or unsubstituted morpholine, substituted or unsubstituted piperazine, boronic acid (B(OH) 2 ), substituted or unsubstituted 1,3,2-dioxaborlane.

2 . The antiparasitic compound of claim 1 , wherein X is O.

3 . The antiparasitic compound of claim 2 , wherein R 1 is ethyl, propyl, iso-propyl, cyclopropyl, butyl, isobutyl, sec-butyl or tert-butyl.

4 . The antiparasitic compound of claim 3 , wherein R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from H, F, CF 3 , SF 5 , substituted or unsubstituted morpholine, substituted or unsubstituted piperazine, boronic acid (B(OH) 2 ), substituted or unsubstituted 1,3,2-dioxaborlane.

5 . The antiparasitic compound of claim 4 , wherein R 2 and R 6 are H, and R 3 , R 4 , and R 5 are F.

6 . The antiparasitic compound of claim 4 , wherein R 2 , R 3 , R 4 , R 5 , and R 6 are fluorine.

7 . The antiparasitic compound of claim 4 , wherein R 5 is CF 3 , SF 5 , boronic acid, or 4,4,5,5-tetramethyl-1,3,2-dioxaborlane and R 2 , R 3 , R 4 , and R 6 are H.

8 . The antiparasitic compound of claim 4 , wherein R 2 , R 3 , R 5 , and R 6 are H, and R 4 is morpholine, methyl-piperazine, SF 5 , boronic acid, or 4,4,5,5-tetramethyl-1,3,2-dioxaborlane.

9 . The antiparasitic compound of claim 3 , wherein R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from H, Cl, Br, F, and CF 3 .

10 . The antiparasitic compound of claim 9 , wherein one of R 2 , R 3 , R 4 , R 5 , and R 6 is CF 3 , another of R 2 , R 3 , R 4 , R 5 , and R 6 is Cl or Br, and the remainder of R 2 , R 3 , R 4 , R 5 , and R 6 are H.

11 . The antiparasitic compound of claim 1 , wherein X is N.

12 . The antiparasitic compound of claim 11 , wherein R 1 is ethyl, propyl, iso-propyl, cyclopropyl, butyl, isobutyl, sec-butyl or tert-butyl.

13 . The antiparasitic compound of claim 12 , wherein R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from H, F, CF 3 , SF 5 , substituted or unsubstituted morpholine, substituted or unsubstituted piperazine, boronic acid (B(OH) 2 ), substituted or unsubstituted 1,3,2-dioxaborlane.

14 . The antiparasitic compound of claim 13 , wherein R 2 and R 6 are H, and R 3 , R 4 , and R 5 are F.

15 . The antiparasitic compound of claim 13 , wherein R 2 , R 3 , R 4 , R 5 , and R 6 are fluorine.

16 . The antiparasitic compound of claim 13 , wherein R 5 is CF 3 , SF 5 , boronic acid, or 4,4,5,5-tetramethyl-1,3,2-dioxaborlane and R 2 , R 3 , R 4 , and R 6 are H.

17 . The antiparasitic compound of claim 13 , wherein R 2 , R 3 , R 5 , and R 6 are H, and R 4 is morpholine, methyl-piperazine, SF 5 , boronic acid, or 4,4,5,5-tetramethyl-1,3,2-dioxaborlane.

18 . The antiparasitic compound of claim 12 , wherein R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from H, Cl, Br, F, and CF 3 .

19 . The antiparasitic compound of claim 18 , wherein one of R 2 , R 3 , R 4 , R 5 , and R 6 is CF 3 , another of R 2 , R 3 , R 4 , R 5 , and R 6 is Cl or Br, and the remainder of R 2 , R 3 , R 4 , R 5 , and R 6 are H.

20 . A method of treating a parasitic infection comprising administering the antiparasitic compound of claim 1 to a subject in need thereof.

21 . A method of making the antiparasitic compound of claim 1 comprising a one-pot synthesis comprising:
a) mixing 2,2,6,6-tetramethylpiperidine, a 2-cyanoacetate ester comprising R 1 , and sulfur in ethanol under heat to form a reaction solution; and;
b) adding 2-R 2 , 3-R 3 , 4-R 4 —, 5-R 5 , 6-R 6 -benzoyl chloride to the reaction solution at room temperature.

Assignees

• Univ Texas

Inventors

• Skouta Rachid
• Maldonado Rosa A

Classifications

• C07F5/025

  Boronic and borinic acid compounds · CPC title

• C07D495/04 Primary

  Ortho-condensed systems · CPC title

• C07F5/04

  Esters of boric acids · CPC title