Pharmaceutical compositions and treatment methods-7

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, asthma, allergic respiratory disease, allergic rhinitis, subepithelial fibrosis in airway hyperresponsiveness, chronic sinusitis, perennial allergic rhinitis, allergic bronchopulmonary aspergillosis in cystic fibrosis patients, Crohn's disease, ulcerative colitis, inflammatory bowel disease or fibrosing alveolitis, comprising administering to the subject an effective amount of a compound having the structure  
       
         
           
           
               
               
           
         
         wherein R 1  is an ester, a thioester, an ether, a thioether, a carbonate, a carbamate, optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer, wherein the ester, thioester, ether or thioether moiety is substituted with 1, 2, 3 or 4 independently selected —O—, —S—, —NR PR —, —C(O)—, ═O, ═S, —N(R PR ) 2 , —C(O)OR PR , —OC(O)R PR , —OR PR , —SR PR , —NO 2 , —CN, —NHC(O)—, —C(O)NH—, —OC(O)—, —C(O)O—, —O-A8, —S-A8, —C(O)-A8, —OC(O)-A8, —C(O)O-A8, ═N—, —N═, ═N—OH, —OPO 3 (R PR ) 2 , —OSO 3 H 2  or halogen moieties or atoms, where each R PR  is —H, an independently selected protecting group or both R PR  together comprise a protecting group, and A8 is C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 1-4  alkyl-aryl (e.g., benzyl), aryl (e.g. phenyl) or C 0-4  alkyl-C 2-9  heterocycle;  
         R 2  is —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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer;  
         R 3  is —H, —OH, —OR PR , —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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer;  
         R 4  is ═O or ═S;  
         R 5  and R 6  independently are —H, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl group;  
         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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an 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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an 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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an optionally substituted oligosaccharide, a nucleoside, a nucleotide, an oligonucleotide 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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, a halogen, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an optionally substituted oligosaccharide 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 are protecting groups; and  
         R 13  independently are C1-C6 alkyl.  
       
     
     
         2 . The method of  claim 1  wherein the compound has the structure  
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 2  wherein R 1  is an ester or thioester that is substituted with independently selected ═O, ═S, —C(O)—, —O—, —S—, —NH—, —OH, —SH, —NHR PR  or —NH 2  moieties, where R PR  is a protecting group and R 3  is —H, —OH, ═O, —SH, ═S or a halogen.  
     
     
         4 . The method of  claim 3  wherein the compound has the structure  
       
         
           
           
               
               
           
         
       
       wherein R 1  is —O—C(O)—CH 2 CH 2 NH 2 , —O—C(O)—CH 2 CH 2 CH 2 NH 2 , —O—C(O)—NH 2 , —O—C(O)—NHCH 3 , —O—C(O)—NHC 2 H 5 , —O—C(O)—NHCH 2 CH 2 CH 3 , —O—C(O)—NHCH 2 CH 2 OCH 2 CH 3 , —O—C(O)—CH 2 OH, —O—C(O)—CH 2 CH 2 OH, —O—C(O)—CH 2 CH 2 CH 2 OH, —O—C(O)—CH 2 SH, —O—C(O)—CH 2 CH 2 SH, —O—C(O)—CH 2 CH 2 CH 2 SH, —O—C(O)—C4 aminoalkyl, —O—C(O)—C6 aminoalkyl, —O—C(O)—C8 aminoalkyl, —O—C(O)—C4 hydroxyalkyl, —O—C(O)—C6 hydroxyalkyl or —O—C(O)—C8 hydroxyalkyl.  
     
     
         5 . The method of  claim 4  wherein the compound has the structure  
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 5  werein the inflammation condition is asthma, allergic respiratory disease, allergic rhinitis, or subepithelial fibrosis in airway hyperresponsiveness.  
     
     
         7 . A method to treat a bone fracture, osteoporosis or a neurological disorder comprising administering to a subject having, or subject to developing the bone fracture, osteoporosis or neurological disorder, an effective amount of a compound having the structure  
       
         
           
           
               
               
           
         
         wherein the dotted lines are optional double bonds;  
         R 1  is —OH, —OR PR , —SH, —SR PR , —NH 2 , —NHR PR , an ester, a thioester, an ether, a thioether, a carbonate, a carbamate, optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer, wherein the ester, thioester, ether or thioether moiety is substituted with 1, 2, 3 or 4 independently selected —O—, —S—, —NR PR —, —C(O)—, ═O, ═S, —N(R PR ) 2 , —C(O)OR PR , —OC(O)R PR , —OR PR , —SR PR , —NO 2 , —CN, —NHC(O)—, —C(O)NH—, —OC(O)—, —C(O)O—, —O-A8, —S-A8, —C(O)-A8, —OC(O)-A8, —C(O)O-A8, ═N—, —N═, ═N—OH, —OPO 3 (R PR ) 2 , —OSO 3 H 2  or halogen moieties or atoms, where each R PR  is —H, an independently selected protecting group or both R PR  together comprise a protecting group, and A8 is C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 1-4  alkyl-aryl (e.g., benzyl), aryl (e.g. phenyl) or C 0-4  alkyl-C 2-9  heterocycle;  
         R 2  is —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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer;  
         R 3  is —H, —OH, —OR PR , —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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer;  
         R 5  and R 6  independently are —H, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl group;  
         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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an 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 3  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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an 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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an optionally substituted oligosaccharide, a nucleoside, a nucleotide, an oligonucleotide or a polymer;  
         R PR  independently are protecting groups;  
         R 13  independently are C1-C6 alkyl; and  
         (a) R 4  in the β-configuration is —OH, —OR PR , —SH, —SR PR , —NH 2 , —NHR PR , an ester, a thioester, an amide, an amino acid, a peptide, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer;  
         R 4  in the α-configuration is —H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or optionally substituted heteroaryl; or  
         (b) R 4  in the α-configuration is —OH, —OR PR , —SH, —SR PR , —NH 2 , —NHR PR , an ester, a thioester, an amide, an amino acid, a peptide, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer;  
         R 4  in the β-configuration is —H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or optionally substituted heteroaryl.  
       
     
     
         8 . The method of  claim 7  wherein (1) a double bond is present at the 5-6 position and a double bond is optionally present at the 1-2 position, (2) wherein hydrogen is present at the 5-position in the α-configuration or the β-configuration, or (3) a double bond is present at the 4-5 position and a double bond is optionally present at the 1-2 position.  
     
     
         9 . The method of  claim 8  wherein R 1  is —OH, —SH, —NH 2 , an ester, a thioester an amide, a carbamate a carbonate or a polymer.  
     
     
         10 . The method of  claim 9  wherein R 2  is —H or optionally substituted alkyl and R 3  is —H, —OH, halogen or optionally substituted alkyl.  
     
     
         11 . The method of  claim 10  wherein R 5  and R 6  independently are —H or optionally substituted alkyl.  
     
     
         12 . The method of  claim 11  wherein R 7  is —CH 2 — or —CH 2 —CH 2 — and R 8  is —CH 2 —.  
     
     
         13 . The method of  claim 12  wherein R 9  is —CH 2 —, —O—, —S— or —NH—.  
     
     
         14 . The method of  claim 13  wherein R 3  is —H, R 5  is —CH 3  or —CH 2 OH and R 6  is —H or —CH 3 .  
     
     
         15 . The method of  claim 7  wherein the compound has the structure  
       
         
           
           
               
               
           
         
       
     
     
         16 . The method of  claim 15  wherein R 4  in the α-configuration is —OH, —OR PR , —SH, —SR PR , —NH 2 , —NHR PR , an ester, a thioester, an amide, an amino acid, a peptide, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer and R 4  in the β-configuration is —H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or optionally substituted heteroaryl.  
     
     
         17 . The method of  claim 16  wherein R 4  in the α-configuration is —OH, —SH, —NH 2 , an ester, a thioester, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer and R 4  in the β-configuration is —H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or optionally substituted heteroaryl.  
     
     
         18 . The method of  claim 17  wherein R 2  and R 3  are —H, R 4  in the α-configuration is —OH, —SH or —NH 2 , R 4  in the β-configuration is —H, —CH 3  or —C≡CH, R 5  is —CH 3 , R 6  is —H or —CH 3  and R 9  is —CH 2 —, —O—, —S— or —NH—.  
     
     
         19 . The method of  claim 18  wherein there is no double bond at the 1-2 position and R 9  is —CH 2 —.  
     
     
         20 . The method of  claim 15  wherein R 4  in the β-configuration is —OH, —OR PR , —SH, —SR PR , —NH 2 , —NHR PR , an ester, a thioester, an amide, an amino acid, a peptide, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer and R 4  in the α-configuration is —H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or optionally substituted heteroaryl.  
     
     
         21 . The method of  claim 20  wherein R 4  in the β-configuration is —OH, —SH, —NH 2 , an ester, a thioester, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide, an optionally substituted oligosaccharide or a polymer and R 4  in the α-configuration is —H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or optionally substituted heteroaryl.  
     
     
         22 . The method of  claim 21  wherein R 2  and R 3  are —H, R 4  in the β-configuration is —OH, —SH or —NH 2 , R 4  in the α-configuration is —H, —CH 3  or —C≡CH, R 5  is —CH 3 , R 6  is —H or —CH 3  and R 9  is —CH 2 —, —O—, —S— or —NH—.  
     
     
         23 . The method of  claim 22  wherein there is no double bond at the 1-2 position and R 9  is —CH 2 —.  
     
     
         24 . The method of  claim 7  wherein the compound is 3α,17β-dihydroxyandrost-5-ene, 3α,17β-dihydroxy-19-norandrost-5-ene, 3α,17β-dihydroxyandrost-4-ene, 3α,17β-dihydroxy-19-norandrost-4-ene, 3α,17β-dihydroxy-5α-androstane, 3α,17β-dihydroxy-19-nor-5α-androstane, 3α,17β-dihydroxy-5β-androstane, 3α,17β-dihydroxy-19-nor-5β-androstane, 3α,17β-dihydroxyandrost-1,5-diene, 3α,17β-dihydroxy-19-norandrost-1,5-diene, 3β,17β-dihydroxyandrost-5-ene, 3β,17β-dihydroxy-19-norandrost-5-ene, 3β,17β-dihydroxyandrost-4-ene, 3β,17β-dihydroxy-19-norandrost-4-ene, 3β,17β-dihydroxy-5α-androstane, 3β,17β-dihydroxy-19-nor-5α-androstane, 3β,17β-dihydroxy-5β-androstane, 3β,17β-dihydroxy-19-nor-5β-androstane, 3β,17β-dihydroxyandrost-1,5-diene, 3β,17β-dihydroxy-19-norandrost-1,5-diene, 3β,17α-dihydroxyandrost-5-ene, 3β,17α-dihydroxy-19-norandrost-5-ene, 3β,17α-dihydroxyandrost-4-ene, 3β,17α-dihydroxy-19-norandrost-4-ene, 3β,17α-dihydroxy-5α-androstane, 3β,17α-dihydroxy-19-nor-5α-androstane, 3β,17α-dihydroxy-5β-androstane, 3β,17α-dihydroxy-19-nor-5β-androstane, 3β,17α-dihydroxyandrost-1,5-diene, 3β,17α-dihydroxy-19-norandrost-1,5-diene, 3α,17β-dihydroxy-5α-androst-1-ene, 3α,17β-dihydroxy-19-nor-5α-androst-1-ene, 3α,17β-dihydroxy-5β-androst-1-ene, 3α,17β-dihydroxy-19-nor-5β-androst-1-ene, 3β,17β-dihydroxy-5α-androst-1-ene, 3β,17β-dihydroxy-19-nor-5α-androst-1-ene, 3β,17β-dihydroxy-5β-androst-1-ene, 3β,17β-dihydroxy-19-nor-5β-androst-1-ene, 3β,17α-dihydroxy-5α-androst-1-ene, 3β,17α-dihydroxy-19-nor-5α-androst-1-ene, 3β,17α-dihydroxy-5β-androst-1-ene, 3β,17α-dihydroxy-19-nor-5β-androst-1-ene, 3α,17β-dihydroxyandrost-1,4-diene, 3α,17β-dihydroxy-19-norandrost-1,4-diene, 3β,17β-dihydroxyandrost-1,4-diene, 3β,17β-dihydroxy-19-norandrost-1,4-diene, 3β,17α-dihydroxyandrost-1,4-diene, 3β,17α-dihydroxy-19-norandrost-1,4-diene or an analog of any of these compounds wherein (1) one or both of R 8  and R 9  independently are —O—, —S—, —NH— or are absent and/or (2) R 7  is —O—, —S—, —NH— or —CH 2 —CH 2 — and/or (3) the analog is an 18-nor analog.  
     
     
         25 . The method of  claim 7  wherein the neurological disorder is Alzheimer's disease, Parkinson's disease or Multiple Sclerosis.  
     
     
         26 . A pharmaceutical formulation comprising one or more excipients and an analog of a compound selected from the group consisting of 3α,17β-dihydroxyandrost-5-ene, 3α,17β-dihydroxy-19-norandrost-5-ene, 3α,17β-dihydroxyandrost-4-ene, 3α,17β-dihydroxy-19-norandrost-4-ene, 3α,17β-dihydroxy-5α-androstane, 3α,17β-dihydroxy-19-nor-5α-androstane, 3α,17β-dihydroxy-5β-androstane, 3α,17β-dihydroxy-19-nor-5β-androstane, 3α,17β-dihydroxyandrost-1,5-diene, 3α,17β-dihydroxy-19-norandrost-1,5-diene, 3β,17β-dihydroxy-19-norandrost-5-ene, 3β,17β-dihydroxyandrost-4-ene, 3β,17β-dihydroxy-19-norandrost-4-ene, 3β,17β-dihydroxy-5α-androstane, 3β,17β-dihydroxy-19-nor-5α-androstane, 3β,17β-dihydroxy-5β-androstane, 3β,17β-dihydroxy-19-nor-5β-androstane, 3β,17β-dihydroxyandrost-1,5-diene, 3β,17β-dihydroxy-19-norandrost-1,5-diene, 3β,17α-dihydroxyandrost-5-ene, 3β,17α-dihydroxy-19-norandrost-5-ene, 3β,17α-dihydroxyandrost-4-ene, 3β,17α-dihydroxy-19-norandrost-4-ene, 3β,17α-dihydroxy-5α-androstane, 3β,17α-dihydroxy-19-nor-5α-androstane, 3β,17α-dihydroxy-5β-androstane, 3β,17α-dihydroxy-19-nor-5β-androstane, 3β,17α-dihydroxyandrost-1,5-diene, 3β,17α-dihydroxy-19-norandrost-1,5-diene, 3α,17β-dihydroxy-5α-androst-1-ene, 3α,17β-dihydroxy-19-nor-5α-androst-1-ene, 3α,17β-dihydroxy-5β-androst-1-ene, 3α,17β-dihydroxy-19-nor-5β-androst-1-ene, 3β,17β-dihydroxy-5α-androst-1-ene, 3β,17β-dihydroxy-19-nor-5α-androst-1-ene, 3β,17β-dihydroxy-5β-androst-1-ene, 3β,17β-dihydroxy-19-nor-5β-androst-1-ene, 3β,17α-dihydroxy-5α-androst-1-ene, 3β,17α-dihydroxy-19-nor-5α-androst-1-ene, 3β,17α-dihydroxy-5β-androst-1-ene, 3β,17α-dihydroxy-19-nor-5β-androst-1-ene, 3α,17β-dihydroxyandrost-1,4-diene, 3α,17β-dihydroxy-19-norandrost-1,4-diene, 3β,17β-dihydroxyandrost-1,4-diene, 3β,17β-dihydroxy-19-norandrost-1,4-diene, 3β,17α-dihydroxyandrost-1,4-diene and 3β,17α-dihydroxy-19-norandrost-1,4-diene, wherein the analog is a 2-oxa, 2-thia, 2-aza, 2-nor, 11-oxa, 11-thia, 11-aza, 11-nor, 15-oxa, 15-thia, 15-aza, 15-homo or 18-nor analog an optionally wherein the analog is substituted at the 7-position and/or at the 16-position with an independently selected substituent selected from the group consisting of —OH, ═O, —SH, ═S, —NH 2 , ester, ether, thioester, thioether, halogen, optionally substituted monosaccharide, optionally substituted oligosaccharide, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl and optionally substituted heterocycle.