3-Nitrogen-6,7-dioxygen steroids and uses related thereto

1 . A compound of the formula

and pharmaceutically acceptable salts, solvates, stereoisomers and prodrugs thereof, in isolation or in mixture, where independently at each occurrence:

R 1 and R 2 are selected from hydrogen, oxygen so as to form nitro or oxime, amino, —SO 3 —R, and organic groups having 1-30 carbons and optionally containing 1-6 heteroatoms selected from nitrogen, oxygen, phosphorous, silicon, and sulfur, where R 2 may be a direct bond to numeral 3, or R 1 and R 2 may, together with the N to which they are both bonded, form a heterocyclic structure that may be part of an organic group having 1-30 carbons and optionally containing 1-6 heteroatoms selected from nitrogen, oxygen and silicon; or R 1 may be a 2 or 3 atom chain to numeral 2 so that —N—R 1 — forms part of a fused bicyclic structure to ring A;

R 3 and R 4 are selected from direct bonds to 6 and 7 respectively so as to form carbonyl groups, hydrogen, or a protecting group such that R 3 and/or R 4 is part of hydroxyl or carbonyl protecting group;

numerals 1 through 17 each represent a carbon, where carbons at numerals 1, 2, 4, 11, 12, 15, 16 and 17 may be independently substituted with

(a) one of: ═O, ═C(R 5 )(R 5 ), ═C═C(R 5 )(R 5 ), —C(R 5 )(R 5 )(C(R 5 )(R 5 )) n — and —(O(C(R 5 )(R 5 )) n O)— wherein n ranges from 1 to about 6; or

(b) two of the following, which are independently selected: —X, —N(R 1 )(R 2 ), —R 5 and —OR 6 ;

and where carbons at numerals 5, 8, 9, 10, 13 and 14 may be independently substituted with one of —X, —R 5 , —N(R 1 )(R 2 ) or —OR 6 ;

in addition to the —OR 3 and —OR 4 groups as shown, each of carbons 6 and 7 may be independently substituted with one of —X, —N(R 1 )(R 2 ), —R 5 or —OR 6 ;

each of rings A, B, C and D is independently fully saturated, partially saturated or fully unsaturated;

R 5 at each occurrence is independently selected from H, X, and C 1-30 organic moiety that may optionally contain at least one heteroatom selected from the group consisting of boron, halogen, nitrogen, oxygen, silicon and sulfur; where two geminal R 5 groups may together form a ring with the carbon atom to which they are both bonded;

R 6 is H or a protecting group such that —OR 6 is a protected hydroxyl group, where vicinal —OR 6 groups may together form a cyclic structure that protects vicinal hydroxyl groups, and where geminal —OR 6 groups may together form a cyclic structure that protects a carbonyl group; and

X represents fluoride, chloride, bromide and iodide.

2 . The compound of claim 1 wherein

numerals 1 through 16 each represent a carbon, where carbons at numerals 1, 2, 4, 1, 12, 15 and 16 may be independently substituted with

(a) one of: ═O, ═C(R 5 )(R 5 ), ═C═C(R 5 )(R 5 ), —C(R 5 )(R 5 )(C(R 5 )(R 5 )) n — and —(O(C(R 5 )(R 5 )) n O)— wherein n ranges from 1 to about 6; or

(b) two of the following, which are independently selected: —X, —N(R 1 )(R 2 ), —R 5 and —OR 6 ; and

numeral 17 represents a carbon substituted with

(a) one of: ═C(R 5a )(R 5a ), ═C═C(R 5a )(R 5a ), and —C(R 5a )(R 5a )(C(R 5a )(R 5a )) n — wherein n ranges from 1 to about 6; or

(b) two of the following, which are independently selected: —X, —N(R 1 )(R 2 ) and —R 5a ;

where R 5a at each occurrence is independently selected from H, X, and C 1-30 organic moiety that may optionally contain at least one heteroatom selected from the group consisting of boron, halogen, nitrogen, silicon and sulfur; where two geminal R 5 groups may together form a ring with the carbon atom to which they are both bonded.

3 . The compound of claim 2 wherein R 5a at each occurrence is independently selected from C 1-30 hydrocarbon, C 1-30 halocarbon, C 1-30 hydrohalocarbon, H, and X.

4 . The compound of claim 2 wherein R 5a at each occurrence is independently selected from C 1-10 hydrocarbon, C 1-10 halocarbon, C 1-10 hydrohalocarbon, H, and X.

5 .- 7 . (canceled)

8 . The compound of claim 1 wherein

R 1 and R 2 are hydrogen;

R 3 and R 4 are selected from direct bonds to 6 and 7 respectively so as to form carbonyl groups, hydrogen, or a protecting group such that R 3 and/or R 4 is part of hydroxyl or carbonyl protecting group; and in addition to the —OR 3 and —OR 4 groups as shown, each of carbons 6 and 7 is substituted with hydrogen unless precluded because —OR 3 or —OR 4 represent a carbonyl group;

carbons at numerals 1, 2, 4, 11, 12, 15 and 16 are each substituted with two hydrogens unless said carbon is part of an unsaturated bond;

carbons at numerals 5, 8, 9 and 14 are each substituted with one hydrogen unless said carbon is part of an unsaturated bond;

carbon at numeral 10 is substituted with methyl;

carbon at number 13 is substituted with methyl unless it is part of an unsaturated bond;

carbon at numeral 17 is substituted with

(a) one of: ═O, ═C(R 5 )(R 5 ), ═C═C(R 5 )(R 5 ), —C(R 5 )(R 5 )(C(R 5 )(R 5 )) n — and —(O(C(R 5 )(R 5 )) n O)— wherein n ranges from 1 to about 6; or

(b) two of the following, which are independently selected: —X, —N(R 1 )(R 2 ), —R 5 and —OR 6 ;

each of rings A, B, C and D is independently fully saturated, partially saturated or fully unsaturated;

R 5 at each occurrence is independently selected from H, X, and C 1-30 organic moiety that may optionally contain at least one heteroatom selected from the group consisting of boron, halogen, nitrogen, oxygen, silicon and sulfur; where two geminal R 5 groups may together form a ring with the carbon atom to which they are both bonded;

R 6 is H or a protecting group such that —OR 6 is a protected hydroxyl group, where vicinal —OR 6 groups may together form a cyclic structure that protects vicinal hydroxyl groups, and where geminal —OR 6 groups may together form a cyclic structure that protects a carbonyl group; and

X represents fluoride, chloride, bromide and iodide.

9 .- 16 . (canceled)

17 . The compound of claim 1 wherein the carbon at numeral 17 is substituted with ═C(R 5 )(R 5 ) and R 5 is selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 hydroxyalkyl, and —CO 2 —C 1-6 alkyl; wherein the carbon at numeral 17 is substituted with C 1-6 alkyl or C 1-6 haloalkyl; or wherein the carbon at numeral 17 is substituted with —OR 6 or ═O, wherein R 6 is hydrogen.

18 . The compound of claim 1 wherein the carbon at numeral 17 is substituted with C 1-6 alkyl or C 1-6 haloalkyl.

19 . The compound of claim 1 wherein the carbon at numeral 17 is substituted with —OR 6 or ═O, wherein R 6 is hydrogen.

20 . The compound of claim 1 wherein R 1 is selected from —C(═O)—R 7 , —C(═O)NH—R 7 ; —SO 2 —R 7 ; wherein R 7 is selected from alkyl, heteroalkyl, aryl and heteroaryl.

21 . The compound of claim 20 wherein R 7 is selected from C 1-10 hydrocarbyl; or biotin.

22 .- 23 . (canceled)

24 . The compound of claim 1 wherein R 1 is hydrogen and R 2 comprises a carbocycle.

25 .- 26 . (canceled)

27 . The compound of claim 1 wherein R 1 is hydrogen and R 2 is a C 1-10 hydrocarbyl or heteroalkyl.

28 .- 29 . (canceled)

30 . The compound of claim 1 wherein R 1 is hydrogen and R 2 is —CH 2 —R 7 wherein R 7 is selected from alkyl, heteroalkyl, aryl and heteroaryl.

31 . (canceled)

32 . The compound of claim 1 wherein each of R 1 and R 2 is hydrogen.

33 . The compound of claim 1 wherein each of R 3 and R 4 is hydrogen.

34 .- 37 . (canceled)

38 . The compound of claim 1 wherein —N(R 1 )(R 2 ) is in a salt form and the salt is a halogen or acetate salt.

39 .- 40 . (canceled)

41 . The compound of claim 1 wherein at least one of the carbons at numerals 10 and 13 are substituted with methyl.

42 .- 52 . (canceled)

53 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, excipient or diluent.

54 . A method of treating inflammation asthma allergic disease, allergic disease, chronic obstructive pulmonary disease, atopic dermatitis, solid tumours, AIDS, ischemia reperfusion injury or cardiac arrhythias comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .

55 .- 63 . (canceled)