1,3-benzothiazinone, sulfoxide, and sulfone compounds with electrophilic substituent

Patent metadata

Field	Value
Publication number	US-9708339-B2
Application number	US-201514734657-A
Country	US
Kind code	B2
Filing date	Jun 9, 2015
Priority date	Jun 9, 2014
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

A compound, having the following formula:

or resonance form thereof, or salt thereof, or salt of resonance form thereof is provided, wherein E includes an electrophilic site, and wherein R 1 -R 4 and n are defined herein. Compositions and methods including the compound are also provided.

First claim

What is claimed is:

1. A compound, having the following formula:

or resonance form thereof, or salt thereof, or salt of resonance form thereof;
wherein R 1 -R 4 are each independently hydrogen, an alkyl group, a cycloalkyl group, a cycloalkenyl group, a halo group, an alkenyl group, an alkynyl group, an aryl group, a hydroxy group, an acyl group, an oxo group, a mercapto group, an alkylthio group, an alkoxy group, a heterocyclic group, a heteroaryl group, a heteroarylcarbonyl group, an aryloxy group, a heteroaryloxy group, an aralkyl group, a heteroaralkyl group, an aralkoxy group, a heteroaralkoxy group, an amino group, an alkylamino group, a dialkylamino group, an amidine group, an amide group, a carbamoyl group, an alkylcarbonyl group, an alkoxycarbonyl group, an alkylaminocarbonyl group, a dialkylamino carbonyl group, an arylcarbonyl group, an aryloxycarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, perhaloalkyl group, a perhaloalkoxy group, a perhalocycloalkyl group, a perhaloalkenyl group, a perhaloalkynyl group, a perhaloaryl group, a perhaloaralkyl group, or combination thereof;
wherein R 3 and R 4 may be taken together with the nitrogen to which they are attached to form a substituted or unsubstituted, saturated or unsaturated, mono-, bi-, tri-, or polycyclic heterocyclic group;
wherein each group may be optionally and independently straight, branched substituted, or unsubstituted; and wherein one or more than one atom in each group may be optionally and independently replaced with one or more independent heteroatoms;
wherein n is 0, 1, or 2.

2. The compound of claim 1 , wherein R 1 -R 4 are each independently hydrogen, alkyl, allyl, cycloalkyl, aryl, acyl, aroyl, or combination thereof,
said alkyl and allyl being independently linear, branched, substituted, unsubstituted, or combination thereof,
said cycloalkyl being substituted or unsubstituted, the alkyl portion of which being linear, branched, substituted, unsubstituted, or combination thereof,
said aryl, acyl, and aroyl being independently substituted or unsubstituted;
and wherein R 3 and R 4 taken together with the nitrogen to which they are attached may optionally form a heterocyclic group, said heterocyclic group being substituted, unsubstituted, saturated, unsaturated, or combination thereof.

3. The compound of claim 1 , wherein one or more than one atom in one or more of R 1 -R 4 is independently replaced with one or more independent heteroatom.

4. The compound of claim 1 , wherein one or more than one carbon in one or more of R 1 -R 4 is independently replaced with one or more independent heteroatom selected from the group consisting of N, O, S, or combination thereof.

5. The compound of claim 1 , wherein R 1 -R 4 are independently hydrogen, alkyl, substituted alkyl, linear alkyl, branched alkyl, allyl, substituted allyl, heteroalkyl, cycloalkyl, aryl, substituted aryl, heteroaryl, acyl, aroyl, heteroaroyl, or combination thereof.

6. The compound of claim 1 , wherein R 3 and R 4 taken together with the nitrogen to which they are attached form a C 3 -C 10 heterocyclic group, said heterocyclic group being substituted, unsubstituted, saturated, unsaturated, or combination thereof.

7. The compound of claim 1 wherein R 3 and R 4 taken together with the nitrogen to which they are attached form a C 3 -C 6 heterocyclic group.

8. The compound of claim 1 , having one of the following formulas:

wherein R 5 is hydrogen, an alkyl group, a cycloalkyl group, a cycloalkenyl group, a halo group, an alkenyl group, an alkynyl group, an aryl group, a hydroxy group, an acyl group, an oxo group, a mercapto group, an alkylthio group, an alkoxy group, a heterocyclic group, a heteroaryl group, a heteroarylcarbonyl group, an aryloxy group, a heteroaryloxy group, an aralkyl group, a heteroaralkyl group, an aralkoxy group, a heteroaralkoxy group, an amino group, an alkylamino group, a dialkylamino group, an amidine group, an amide group, a carbamoyl group, an alkylcarbonyl group, an alkoxycarbonyl group, an alkylaminocarbonyl group, a dialkylamino carbonyl group, an arylcarbonyl group, an aryloxycarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, perhaloalkyl group, a perhaloalkoxy group, a perhalocycloalkyl group, a perhaloalkenyl group, a perhaloalkynyl group, a perhaloaryl group, a perhaloaralkyl group, or combination thereof; and
wherein each group may be optionally and independently straight, branched substituted, or unsubstituted; and wherein one or more than one atom in each group may be optionally and independently replaced with one or more independent heteroatoms.

9. A pharmaceutical composition, comprising the compound of claim 1 and a physiologically acceptable carrier.

10. A method of treating a subject known or suspected to need treatment for one or more maladies related to non-pathogenic mycobacterial strain, M. smegmatis, M. vaccae, M. aurum , Gram positive bacteria, S. aureus, M. luteus , Gram negative bacteria, P. aeruginosa, A. baumanii , pathogenic mycobacterial strain, M. tuberculosis, M. bovis, M. marinum, M. kansasaii , H37Rv, M. africanum, M. canetti, M. caprae, M. microti, M. mungi, M. pinnipedii , myobacterium tuberculosis complex, tuberculosis, or combination thereof, comprising administering the compound of claim 1 to said subject, to treat said subject.

11. A method of treating a subject known or suspected to need treatment for one or more maladies related to non-pathogenic mycobacterial strain, M. smegmatis, M. vaccae, M. aurum , Gram positive bacteria, S. aureus, M. luteus , Gram negative bacteria, P. aeruginosa, A. baumanii , pathogenic mycobacterial strain, M. tuberculosis, M. bovis, M. marinum, M. kansasaii , H37Rv, M. africanum, M. canetti, M. caprae, M. microti, M. mungi, M. pinnipedii , myobacterium tuberculosis complex, tuberculosis, or combination thereof, comprising administering the composition of claim 9 to said subject, to treat said subject.

12. The compound of claim 1 , wherein R 1 and R 2 are hydrogen.

13. The compound of claim 1 , wherein n=0.

14. The compound of claim 1 , wherein n=1.

15. The compound of claim 1 , wherein n=2.

16. The compound of claim 1 , wherein in the group:

R 3 and R 4 are taken together to form a heterocyclic group having the following cyclic structure (II):

wherein x is 1-10, and R 6 is hydrogen, an alkyl group, a cycloalkyl group, a cycloalkenyl group, an alkenyl group, an alkynyl group, an aryl group, a heterocyclic group, a heteroaryl group, an aralkyl group, a heteroaralkyl group, oxidized form thereof, or combination thereof.

17. The compound of claim 1 , wherein R 3 and R 4 taken together with the nitrogen to which they are attached form a substituted or unsubstituted, saturated or unsaturated, mono-, bi-, tri-, or polycyclic heterocyclic group.

18. The compound of claim 1 , wherein R 3 and R 4 taken together with the nitrogen to which they are attached form a substituted or unsubstituted, saturated or unsaturated, mono- bi-, tri-, or polycyclic C 3 -C 20 heterocyclic group.

19. T

Assignees

• Univ Notre Dame Du Lac

Inventors

• Miller Marvin J
• Tiwari Rohit

Classifications

• C07D491/113 Primary

  with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring · CPC title

• C07D279/08

  condensed with carbocyclic rings or ring systems · CPC title