Boron containing small molecules as antiprotozoal agents

Patent metadata

Field	Value
Publication number	US-9440994-B2
Application number	US-85235110-A
Country	US
Kind code	B2
Filing date	Aug 6, 2010
Priority date	Aug 14, 2009
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

This invention provides, among other things, novel compounds useful for treating protozoal infections, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent. The exemplary compounds have the following formula:

wherein X is selected from the group consisting of substituted phenyl, substituted or unsubstituted heteroaryl and unsubstituted cycloalkyl; R 3a is selected from the group consisting of H, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl and unsubstituted C 3 or C 4 or C 5 or C 6 cycloalkyl; R 3b is selected from the group consisting of H, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl and unsubstituted C 3 or C 4 or C 5 or C 6 cycloalkyl;

with the proviso that R 3a and R 3b , along with the atom to which they are attached, are optionally joined to form a 3 or 4 or 5 or 6 membered ring, with the proviso that R 3a and R 3b cannot both be H, or a salt thereof.

First claim

What is claimed is:

1. A compound having a structure according to the following formula:

wherein
X is selected from the group consisting of substituted phenyl, substituted or unsubstituted heteroaryl and unsubstituted cycloalkyl; and
R 3a and R 3b , along with the atom to which they are attached, are joined to form cyclopropyl or cyclobutyl or cyclopentyl;

or a salt thereof.

2. The compound of claim 1 , or a salt thereof, having a structure according to the following formula:

wherein R 2 , R 3 , R 4 , R 5 and R 6 are the same or different and are each selected from the group consisting of H, halogen, cyano, nitro, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkoxy, halosubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl, halosubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkoxy, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkylthio, unsubstituted phenyl, NR 8 R 9 , —SO 2 (R 7 ) and —SO 2 N(R 7 )(R 8 )
wherein
R 7 is H or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl;
R 8 is H or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl; and
R 9 is selected from the group consisting of H, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl and —C(O)R 10
wherein
R 10 is unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl

with the proviso that R 2 , R 3 , R 4 , R 5 and R 6 cannot all be H.

3. The compound of claim 2 , or a salt thereof, having a structure according to the following formula:

wherein R 2 , R 3 , R 4 , R 5 and R 6 are the same or different and are each selected from the group consisting of H, F, Cl, CN, NO 2 , —CH 3 , —CH 2 CH 3 , CH(CH 3 ) 2 , C(CH 3 ) 3 , CF 3 , —OCH 3 , —OCH 2 CH 3 , —OCF 3 , —N(CH 3 ) 2 , —NH(C(O)CH 3 ), —SCH 3 , —S(O) 2 CH 3 , and —S(O) 2 N(CH 3 ) 2
with the proviso that R 2 , R 3 , R 4 , R 5 and R 6 cannot all be H.

4. The compound of claim 2 , or a salt thereof, having a structure according to the following formula:

wherein one member selected from the group consisting of R 2 , R 3 , R 4 , R 5 and R 6 is halogen or cyano or nitro or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkoxy or halosubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl or halosubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkoxy or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkylthio or unsubstituted phenyl or NR 8 R 9 or —SO 2 (R 7 ) or —SO 2 N(R 7 )(R 8 )
wherein
R 7 is H or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl;
R 8 is H or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl; and
R 9 is a member selected from H, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl and —C(O)R 10
wherein
R 10 is unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl

and the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

5. The compound of claim 2 , or a salt thereof, having a structure according to the following formula:

wherein one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is F, Cl, CN, NO 2 , —CH 3 , —CH 2 CH 3 , CH(CH 3 ) 2 , C(CH 3 ) 3 , CF 3 , —OCH 3 , —OCH 2 CH 3 , —OCF 3 , —N(CH 3 ) 2 , —NH(C(O)CH 3 ), —SCH 3 , —S(O) 2 CH 3 , or —S(O) 2 N(CH 3 ) 2
and the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

6. The compound of claim 2 , or a salt thereof,
wherein
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is halogen or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl or halosubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl, and
the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

7. The compound of claim 6 , or a salt thereof,
wherein
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is a member selected from F, Cl, Br, I, CH 3 , CF 3 and OCH 3 ; and
the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

8. The compound of claim 7 , or a salt thereof,
wherein
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is F or Cl or CH 3 or CF 3 ; and
the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

9. The compound of claim 2 , or a salt thereof,
wherein
two members selected from R 2 , R 3 , R 4 , R 5 and R 6 are the same or different and are each selected from halogen; and
the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

10. The compound of claim 2 , or a salt thereof,
wherein
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is halogen;
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is halogen or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl or halosubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl; and
the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

11. The compound of claim 10 , or a salt thereof,
wherein
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is halogen;
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is F or Cl or Br or I or CH 3 or CF 3 or OCH 3 ; and
the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

12. The compound of claim 2 , or a salt thereof,
wherein
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is F;
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is halogen or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl or halosubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl; and
the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

13. The compound of claim 12 , or a salt thereof,
wherein
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is F; and
one member selected from R 2 , R 3 , R 4 , R 5 and R 6 is Cl or CH 3 or CF 3 ; and
the remaining members of R 2 , R 3 , R 4 , R 5 and R 6 are H.

14. The compound of claim 2 , or a salt thereof, having a structure according to the following formula:

wherein
R 2 is a member selected from halogen, cyano, nitro, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkoxy, halosubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl, halosubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkoxy, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkylthio, unsubstituted phenyl, NR 8 R 9 , —SO 2 (R 7 ) and —SO 2 N(R 7 )(R 8 )
wherein
R 7 is H or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl;
R 8 is H or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl; and
R 9 is a member selected from H, unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl and —C(O)R 10
wherein
R 10 is unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl.

15. The compound o

Assignees

• Chen Daitao
• Orr Matthew
• Sligar Jessica
• Jacobs Robert
• Plattner Jacob J
• Anacor Pharmaceuticals Inc

Inventors

• Chen Daitao
• Orr Matthew
• Sligar Jessica
• Jacobs Robert
• Plattner Jacob J

Classifications

• A61P33/02

  Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis · CPC title

• C07F5/025 Primary

  Boronic and borinic acid compounds · CPC title

• A61K31/69

  Boron compounds · CPC title

• A01N55/08

  containing boron · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title