Asthma and colitis treatment methods

Abstract

The invention provides compositions comprising formula 1 steroids, e.g., 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16α-bromo-3β-hydroxy-5α-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

1 . A method to treat a subject having, or subject to developing, a condition selected from the group consisting atopic asthma, allergic respiratory disease, allergic rhinitis, atopic dermatitis, subepithelial fibrosis in airway hyperresponsiveness, chronic sinusitis, perennial allergic rhinitis, allergic bronchopulmonary aspergillosis in cystic fibrosis patients, fatigue and fibrosing alveolitis, comprising administering to the subject about 0.05 mg/kg/day to about 30 mg/kg/day of 16α-hydroxyepiandrosterone, 3α,16α-dihydroxy-17-oxoandrostane, 16β-bromoepiandrosterone, 16β-iodoepiandrosterone, 3β-hydroxy-7,17-dioxoandrost-5-ene, 3β-acetoxy-7,17-dioxoandrost-5-ene, 3β-propionoxy-7,17-dioxoandrost-5-ene, 3β,7α-dihydroxy-17-oxoandrost-5-ene, 3β,7β-dihydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7α-hydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7β-hydroxy-17-oxoandrost-5-ene, 3β-propionoxy-7α-hydroxy-17-oxoandrost-5-ene, 3β-propionoxy-71-hydroxy-17-oxoandrost-5-ene or a 2-oxa, 2-aza or 2-thia analog of any of these compounds, or 16α-bromoepiandrosterone hemihydrate or a compound having the structure  
       
         
           
           
               
               
           
         
         wherein  
         R 1  is —H, —OH, OR PR , —SH, —SR PR , —N 3 , —NH 2 , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , —C(O)—CH 3 , —F, —Cl, —Br, —I, an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 2  is —OH, —OR PR , ═O, —SH, —SR PR , ═S, —N 3 , —CN, —NO 2 , ═NOH, ═NOC(O)CH 3 , an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 3  is —OH, —OR PR , ═O, —SH, —SR PR , ═S, —N 3 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , ═NOH, ═NOC(O)CH 3 , —C(O)—CH 3 , an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 4  is —OH, —OR PR , —SH, —SR PR , ═S, an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 5  and R 6  independently are —H, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl;  
         R 7  is —CHR 10 —, —CHR 10 —CHR 10 —, —CHR 10 —CHR 10 —CHR 10 —, —CHR 10 —O—CHR 10 —, —CHR 10 —S—CHR 10 —, —CHR 10 —NR PR —CHR 10 —, —O—, —O—CHR 10 —, —S—, —S—CHR 10 —, —NR PR - or —NR PR —CHR 10 —, wherein R 10  independently are —H, —OH, —OR PR , ═O, —SH, —SR PR , ═S, ═CH 2 , —N 3 , —NH 2 , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , ═NOH, ═NOC(O)CH 3 , —C(O)—CH 3 , —F, —Cl, —Br, −I, an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 8  is —CHR 10 —, —CHR 10 —CHR 10 —, —O—, —O—CHR 10 —, —S—, —S—CHR 10 —, —NR PR — or —NR PR —CHR 10 —, or R 8  is absent, leaving a 5-membered ring, wherein R 10  independently are —H, —OH, —OR PR , ═O, —SH, —SR PR , ═S, ═CH 2 , —N 3 , —NH 2 , —N(R PR ) 2 —O—Si—(R 13 ) 3 —CN, —NO 2 , ═NOH, ═NOC(O)CH 3 , —C(O)—CH 3 , —F, —Cl, —Br, —I, an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 9  is —CHR 10 —, —CHR 10 —CHR 10 —, —O—, —O—CHR 10 —, —S—, —S—CHR 10 —, —NR PR - or —NR PR —CHR 10 —, or R 9  is absent, leaving a 5-membered ring, wherein R 10  independently are —H, —SH, —SR PR , ═S, ═CH 2 , —N 3 , —NH 2 , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , ═NOH, ═NOC(O)CH 3 , —C(O)—CH 3 , —F, —Cl, —Br, —I, a thioester, an amide, an amino acid, a peptide, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         D is a heterocycle or a 4-, 5-, 6- or 7-membered ring that comprises saturated carbon atoms, wherein 1, 2 or 3 ring carbon atoms of the 4-, 5-, 6- or 7-membered ring are optionally independently substituted with —O—, —S— or —NR PR - or where 1, 2 or 3 hydrogen atoms of the heterocycle or 1 or 2 hydrogen atoms of the 4-, 5-, 6- or 7-membered ring are substituted with —OR PR , —SR PR , N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, a halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer, or, one more of the ring carbons are substituted with ═O or ═S, or D comprises two 5- or 6-membered rings, wherein the rings are fused or are linked by 1 or 2 bonds;  
         R PR  independently or together are —H or a protecting group; and  
         R 13  independently are C1-C6 alkyl.  
       
     
     
         2 . The method of  claim 1  wherein R 1  is —H, —OH, —SH, an ester, an ether, a thioester or a thioether and R 2  is —OH, ═O, —SH, ═S, an ester, an ether, a thioester or a thioether or wherein the compound is 16α-bromoepiandrosterone hemihydrate, 16α-hydroxyepiandrosterone, 3α,16α-dihydroxy-17-oxoandrostane, 16β-bromoepiandrosterone, 16β-iodoepiandrosterone.  
     
     
         3 . The method of  claim 2  wherein R 3  is —OH and R 4  is —OH, —SH, ═S, an ester, an ether, a thioester or a thioether.  
     
     
         4 . The method of  claim 3  wherein R 5  is —CH 3  or —CH 2 OH and R 6  is —H or —CH 3 , R 7  and R 8  are —CH 2 —, and R 9  is —O—, —S—, —CH 2 — or —CH═ and a double bond is present at the 5-6 position and optionally at the 1-2 position.  
     
     
         5 . The method of  claim 4  wherein R 1  is —OH, —O—C 2 H 5 , —O—CH 2 CH 2 CH 3 , —O—CH 2 CH 2 CH 2 CH 3 , —O—CH(CH 3 )CHCH 3 , —O—C(CH 3 ) 3 , —O—(CH 2 ) 4 CH 3 , —O—C(O)—CH 3 , —O—C(O)—C 2 H 5 , —O—C(O)—CH 2 CH 2 CH 3  or —O—C(O)—CH 2 CH 2 CH 2 CH 3 , R 2  is —OH, ═O, —SH or ═S and the compound has the structure  
       
         
           
           
               
               
           
         
       
       wherein the compound is 16α-bromoepiandrosterone hemihydrate, 16α-hydroxyepiandrosterone, 3α,16α-dihydroxy-17-oxoandrostane, 16β-bromoepiandrosterone or 16β-iodoepiandrosterone.  
     
     
         6 . The method of  claim 5  wherein the condition is atopic asthma, allergic respiratory disease, allergic rhinitis, subepithelial fibrosis in airway hyperresponsiveness, chronic sinusitis, perennial allergic rhinitis or fibrosing alveolitis.  
     
     
         7 . The method of  claim 5  wherein the condition is atopic dermatitis.  
     
     
         8 . The method of  claim 1  wherein the condition is atopic dermatitis, the compound is administered by a parenteral route and the compound is 3β-hydroxy-7,17-dioxoandrost-5-ene, 3β-acetoxy-7,17-dioxoandrost-5-ene, 3β-propionoxy-7,17-dioxoandrost-5-ene, 3β,7α-dihydroxy-17-oxoandrost-5-ene, 3β,7β-dihydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7α-hydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7β-hydroxy-17-oxoandrost-5-ene, 3β-propionoxy-7α-hydroxy-17-oxoandrost-5-ene or 3β-propionoxy-7β-hydroxy-17-oxoandrost-5-ene.  
     
     
         9 . The method of  claim 5  wherein the condition is fatigue.  
     
     
         10 . The method of  claim 1  wherein the condition is fatigue and the compound is 3β-hydroxy-7,17-dioxoandrost-5-ene, 3β-acetoxy-7,17-dioxoandrost-5-ene, 3β-propionoxy-7,17-dioxoandrost-5-ene, 3β,7α-dihydroxy-17-oxoandrost-5-ene, 3β,7β-dihydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7α-hydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7β-hydroxy-17-oxoandrost-5-ene, 3β-propionoxy-7α-hydroxy-17-oxoandrost-5-ene or 3β-propionoxy-7β-hydroxy-17-oxoandrost-5-ene.  
     
     
         11 . A method to treat a subject having, or subject to developing, a condition selected from the group consisting of Crohn's disease, ulcerative colitis and inflammatory bowel disease, comprising administering to the subject an effective amount of 16α-hydroxyepiandrosterone, 3α,16α-dihydroxy-17-oxoandrostane, 16β-bromoepiandrosterone, 16β-iodoepiandrosterone, 3β-hydroxy-7,17-dioxoandrost-5-ene, 3β-acetoxy-7,17-dioxoandrost-5-ene, 3β-propionoxy-7,17-dioxoandrost-5-ene, 3β,7α-dihydroxy-17-oxoandrost-5-ene, 3β,7β-dihydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7α-hydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7β-hydroxy-17-oxoandrost-5-ene, 3β-propionoxy-7α-hydroxy-17-oxoandrost-5-ene, 3β-propionoxy-7β-hydroxy-17-oxoandrost-5-ene, 3β-hydroxy-7,17-dioxoandrost-1,5-diene, 3β-acetoxy-7,17-dioxoandrost-1,5-diene, 3β-propionoxy-7,17-dioxoandrost-1,5-diene, 3β,7α-dihydroxy-17-oxoandrost-1,5-diene, 3β,7α-dihydroxy-17-oxoandrost-1,5-diene, 3β-acetoxy-7α-hydroxy-17-oxoandrost-1,5-diene, 3β-acetoxy-7β-hydroxy-17-oxoandrost-1,5-diene, 3β-propionoxy-7α-hydroxy-17-oxoandrost-1,5-diene, 3β-propionoxy-7β-hydroxy-17-oxoandrost-1,5-diene or a 2-oxa, 2-aza or 2-thia analog of any of these compounds, or 16α-bromoepiandrosterone hemihydrate or a compound having the structure  
       
         
           
           
               
               
           
         
         wherein R 1  is —H, —OH, —OR PR , —SH, —SR PR , —N 3 , —NH 2 , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , —C(O)—CH 3 , —F, —Cl, —Br, —I, an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 2  is —OH, OR PR , ═O, —SH, SR PR , ═S, —N 3 , —CN, —NO 2 , ═NOH, ═NOC(O)CH 3 , an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 3  is —OH, —OR PR , ═O, —SH, —SR PR , ═S, —N 3 , —O—Si—(R 13 ) 3 , —NO 2 , ═NOH, ═NOC(O)CH 3 , —C(O)—CH 3 , an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 4  is —SH, SR PR , ═S, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, a thioether, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 5  and R 6  independently are —H, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl;  
         R 7  is —CHR 10 —, —CHR 10 —CHR 10 —, —CHR 10 —CHR 10 —CHR 10 —, —CHR 10 —O—CHR 10 —, —CHR 10 —S—CHR 10 —, —CHR 10 —NR PR —CHR 10 —, —O—, —O—CHR 10 —, —S—, —S—CHR 10 —, —NR PR — or —NR PR —CHR 10 —, wherein R 10  independently are —H, —OH, —OR PR , ═O, —SH, —SR PR , ═S, ═CH 2 , —N 3 , —NH 2 , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , ═NOH, ═NOC(O)CH 3 , —C(O)—CH 3 , —F, —Cl, —Br, —I, an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 8  is —CHR 10 —, —CHR 10 —CHR 10 —, —O—, —O—CHR 10 —, —S—, —S—CHR 10 —, —NR PR — or —NR PR —CHR 10 —, or R 8  is absent, leaving a 5-membered ring, wherein R 10  independently are —H, —OH, OR PR , ═O, —SH, —SR PR , ═S, ═CH 2 , —N 3 , —NH 2 , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , ═NOH, ═NOC(O)CH 3 , —C(O)—CH 3 , —F, —Cl, —Br, —I, an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         R 9  is —CHR 10 —, —CHR 10 —CHR 10 —, —O—, —O—CHR 10 —, —S—, —S—CHR 10 —, —NR PR — or —NR PR —CHR 10 —, or R 9  is absent, leaving a 5-membered ring, wherein R 10  independently are —H, —SH, SR PR , ═S, ═CH 2 , —N 3 , —NH 2 , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , ═NOH, ═NOC(O)CH 3 , —C(O)—CH 3 , —F, —Cl, —Br, —I, a thioester, an amide, an amino acid, a peptide, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer;  
         D is a heterocycle or a 4-, 5-, 6- or 7-membered ring that comprises saturated carbon atoms, wherein 1, 2 or 3 ring carbon atoms of the 4-, 5-, 6- or 7-membered ring are optionally independently substituted with —O—, —S— or —NR PR — or where 1, 2 or 3 hydrogen atoms of the heterocycle or 1 or 2 hydrogen atoms of the 4-, 5-, 6- or 7-membered ring are substituted with —OR PR , —SR PR , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —NO 2 , an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl, a thioacyl, a carbonate, a carbamate, a thioacetal, a halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl moiety, optionally substituted heteroaryl, optionally substituted monosaccharide, optionally substituted oligosaccharide or a polymer, or, one more of the ring carbons are substituted with ═O or ═S, or D comprises two 5- or 6-membered rings, wherein the rings are fused or are linked by 1 or 2 bonds;  
         R PR  independently or together are —H or a protecting group; and  
         R 13  independently are C1-C6 alkyl.  
       
     
     
         12 . The method of  claim 11  wherein R 1  is —OH, —SH, an ester, an ether, a thioester or a thioether, R 2  is —OH, ═O, —SH, ═S, an ester, an ether, a thioester or a thioether and R 4  is —SH, ═S, a thioester or a thioether.  
     
     
         13 . The method of  claim 12  wherein R 5  is —CH 3  or —CH 2 OH, R 6  is —H or —CH 3  and R 7  and R 8  are —CH 2 —.  
     
     
         14 . The method of  claim 13  wherein R 9  is —O—, —S—, —CH 2 — or —CH═ and a double bond is present at the 5-6 position and optionally at the 1-2 position.  
     
     
         15 . The method of  claim 14  wherein R 1  is —OH, —O—C 2 H 5 , —O—CH 2 CH 2 CH 3 , —O—CH 2 CH 2 CH 2 CH 3 , —O—CH(CH 3 )CHCH 3 , —O—C(CH 3 ) 3 , —O—(CH 2 ) 4 CH 3 , —O—C(O)—CH 3 , —O—C(O)—C 2 H 5 , —O—C(O)—CH 2 CH 2 CH 3  or —O—C(O)—CH 2 CH 2 CH 2 CH 3 , R 2  is —OH, ═O, —SH or ═S and the compound has the structure  
       
         
           
           
               
               
           
         
       
     
     
         16 . The method of  claim 11  wherein the compound is 16α-hydroxyepiandrosterone, 3α, 16α-dihydroxy-17-oxoandrostane, 16β-bromoepiandrosterone, 16β-iodoepiandrosterone, or a 2-oxa, 2-aza or 2-thia analog of any of these compounds, or the compound is 16α-bromoepiandrosterone hemihydrate.  
     
     
         17 . The method of  claim 11  wherein the compound is 3β-hydroxy-7,17-dioxoandrost-5-ene, 3β-acetoxy-7,17-dioxoandrost-5-ene, 3β-propionoxy-7,17-dioxoandrost-5-ene, 3β,7α-dihydroxy-17-oxoandrost-5-ene, 3β,7β-dihydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7α-hydroxy-17-oxoandrost-5-ene, 3β-acetoxy-7β-hydroxy-17-oxoandrost-5-ene, 3β-propionoxy-7α-hydroxy-17-oxoandrost-5-ene, 3β-propionoxy-7β-hydroxy-17-oxoandrost-5-ene or a 2-oxa, 2-aza or 2-thia analog of any of these compounds.