Phosphorus-containing heterocycles and a method for making and using

1. A compound of formula I

or a pharmaceutically acceptable salt thereof, wherein:

ring A is aryl;

X is NR 3 ;

Y is CR 4 ;

Z is CR 4 ;

R 1 is —OH, aryl, heteroaryl, —O-aliphatic, —O-aryl, —O-heteroaryl, —O-heterocyclic, or —O-heteroaliphatic;

R 2 is oxo (═O), or ═S;

R 3 is H, aliphatic, heteroaliphatic, heterocyclic, heteroaryl, acyl, carboxyl ester, or a lone pair of electrons;

each R 4 independently is H, aliphatic, heteroaliphatic, aryl, heterocyclic, heteroaryl, halo, CN, NO 2 , sulfonyl, amino, carboxyl, carboxyl ester, aminosulfonyl, or aminocarbonyl; and

“---” represents a bond that may or may not be present.

2. The compound of claim 1 , wherein R 1 is —OH, aryl, heteroaryl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-cycloalkyl, —O-cycloalkenyl, —O-cycloalkynyl, —O-aryl, —O-heteroaryl, —O-heterocyclic, —O-heterocycloaliphatic, —O-heteroalkyl or —O— heterocycloalkyl.

3. The compound of claim 1 , wherein R 2 is oxo.

4. The compound of claim 1 , wherein R 3 is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heterocycloaliphatic, heteroalkyl, heterocycloalkyl, carboxyl ester, or a lone pair of electrons.

5. The compound of claim 1 , wherein each R 4 independently is H, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocyclic, heterocycloaliphatic, heteroalkyl, heterocycloalkyl, halo, CN, NO 2 , sulfonyl, amino, carboxyl, aminosulfonyl, aminocarbonyl, or —CO 2 R where R is aryl or heteroaryl.

6. The compound of claim 1 , wherein ring A is phenyl, or naphthyl.

7. The compound of claim 6 , wherein ring A is phenyl.

8. The compound of claim 1 , wherein Z is CH.

9. The compound of claim 1 , wherein each R 4 independently is alkyl, cycloalkyl, aryl or heteroaryl.

10. The compound of claim 9 , wherein each R 4 independently is 2-pyridyl, phenyl, 4-NC-phenyl, 4-EtOC(O)-phenyl, 4-methoxyphenyl, 3,5-bis(trifluoromethyl)phenyl, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, n-pentyl or cyclopentyl.

11. The compound of claim 1 , wherein R 1 is —O-phenyl, methoxy, ethoxy, propoxy, cyclopropoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, phenyl, pyridyl, thienyl.

12. The compound of claim 11 , wherein R 1 is —O-phenyl, phenyl, or thienyl.

13. The compound of claim 11 , wherein R 1 is —O-phenyl, and R 2 is oxo.

14. The compound of claim 1 , wherein the compound has a structure according to

wherein

R 5 , R 6 , R 7 and R 8 independently are H, aliphatic, haloalkyl, heteroaliphatic, aryl, heterocyclic, heteroaryl, —O-aliphatic, —O-heteroaliphatic, —O-heterocyclic, —O-heteroaryl, —O-aryl, halo, OH, CN, NO 2 , sulfonyl, amino, carboxyl, carboxyl ester, aminosulfonyl, or aminocarbonyl or any two adjacent groups together form an aliphatic, heterocyclic, aryl or heteroaryl ring.

15. The compound of claim 1 , wherein the compound has a structure according to

wherein L is a bond, aliphatic, aryl, heteroaryl, heteroaliphatic, or heterocyclic; and

each R 5 , R 6 , and R 7 independently is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, aryl, heteroaryl, heterocyclic, heterocycloaliphatic, heteroalkyl, heterocycloalkyl, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-heteroaliphatic, —O-heterocyclic, —O— heteroaryl, —O-aryl, halo, CN, NO 2 , sulfonyl, amino, carboxyl, carboxyl ester, aminosulfonyl, or aminocarbonyl or any two adjacent groups together form an aliphatic, heterocyclic, aryl or heteroaryl ring.

16. The compound of claim 15 , wherein:

L is phenyl; or

each R 5 , R 6 , and R 7 is H; or

L is phenyl and each R 5 , R 6 , and R 7 is H.

17. The compound of claim 1 , wherein the compound is selected from:

4-(2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinin-3-yl)benzonitrile;

ethyl 4-(2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinin-3-yl)benzoate;

2-phenoxy-3-phenyl-1H-benzo[e][1,2]azaphosphinine 2-oxide;

3-(4-methoxyphenyl)-2-phenoxy-1H-benzo[e][1,2]azaphosphinine 2-oxide;

3-pentyl-2-phenoxy-1H-benzo[e][1,2]azaphosphinine 2-oxide;

2-phenoxy-3-(pyridin-2-yl)-1H-benzo[e][1,2]azaphosphinine 2-oxide;

4-(2-oxido-2-phenoxy-1H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-e][1,2]azaphosphinin-3-yl)benzonitrile;

6-(tert-butyl)-2-phenoxy-3-(pyridin-2-yl)-1H-benzo[e][1,2]azaphosphinine 2-oxide;

3-(3,5-bis(trifluoromethyl)phenyl)-6-(tert-butyl)-2-phenoxy-1H-benzo[e][1,2]azaphosphinine 2-oxide;

4-(3-oxido-3-phenoxy-4H-naphtho[1,2-e][1,2]azaphosphinin-2-yl)benzonitrile;

4-(2-oxido-2-phenoxy-1H-naphtho[2,3-e][1,2]azaphosphinin-3-yl)benzonitrile;

4-(2-oxido-2-phenoxy-1H-naphtho[2,1-e][1,2]azaphosphinin-3-yl)benzonitrile;

4,4′-(1,4-phenylenebis(2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinine-8,3-diyl))dibenzonitrile;

4,4′-(1,3-phenylenebis(2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinine-8,3-diyl))dibenzonitrile;

4,4′-(1,2-phenylenebis(2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinine-8,3-diyl))dibenzonitrile;

4-(1-benzyl-2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinin-3-yl)benzonitrile;

4-(1-acetyl-2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinin-3-yl)benzonitrile;

4-(2-oxido-2-phenyl-1H-benzo[e][1,2]azaphosphinin-3-yl)benzonitrile;

4-(2-oxido-2-(thiophen-3-yl)-1H-benzo[e][1,2]azaphosphinin-3-yl)benzonitrile;

4-(1-methyl-2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinin-3-yl)benzonitrile;

4-(1-ethyl-2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinin-3-yl)benzonitrile;

4-(1-isopropyl-2-oxido-2-phenoxy-1H-benzo[e][1,2]azaphosphinin-3-yl)benzonitrile; or

4-(2-oxido-2-(thiophen-2-yl)-1H-benzo[e][1,2]azaphosphinin-3-yl)benzonitrile.