Pharmaceutical compositions and 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.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method to treat a subject having, or susceptible to developing, a pathogen infection, an autoimmune disease, inflammation or allergy, osteoporosis, acute myelitis, sarcoidosis, a cancer, a precancer, a neurological disorder, a wound, a bone fracture, a hemorrhage, a burn, a skin lesion or an immunosuppression condition or an unwanted immune response either or both of which are associated with a chemotherapy, radiation exposure or aging, wherein the method comprises intermittent administration of an effective amount of a compound to the subject, wherein the compound is 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate or the compound has the structure
wherein, the dotted lines are optional double bonds and the hydrogen atom at the 5-position, if present, is in the α-configuration;
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 10 independently are —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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, or,
one more of R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , R 15 , R 17 and R 18 independently are ═O, or,
R 3 and both R 4 together comprise a structure of formula 2
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 —;
R 8 and R 9 independently are —CHR 10 —, —CHR 10 —CHR 10 —, —O—, —O—CHR 10 —, —S—, —S—CHR 10 —, —NR PR — or —NR PR —CHR 10 —, or R 8 or R 9 independently is absent, leaving a 5-membered ring;
R 13 independently are C 1-6 alkyl;
R PR independently are a protecting group;
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 nucleoside, a nucleotide, an oligonucleotide 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, provided that the compound is not 3β-hydroxyandrost-5-ene-17-one, 3β-hydroxyandrost-5-ene-1 7-one 3-sulfate or an ester or ether derivative of either compound and provided that when the compound has the structure
wherein each R A independently is —OH, ═O, an ester or an ether, and R B is —C(O)CH 3 , —OH, ═O, an ester or an ether, then the use of the medicament is for the treatment of a subject having or susceptible to developing an autoimmune disease, inflammation or allergy, osteoporosis, acute myelitis, sarcoidosis, a cancer, a precancer, or an immunosuppression condition or an unwanted immune response either or both of which are associated with a chemotherapy, radiation exposure, a wound, a bone fracture, a hemorrhage, a skin lesion or a burn or the medicament is for the treatment of a human having or susceptible to developing a pathogen infection selected from the group consisting of HIV-1, HIV-2, HTLV-1, HTLV-2, HSV-1, HSV-2, HHV-6, HHV-8, CMV, hepatitis C virus, hepatitis B virus, Western Equine Encephalitis Virus, Japanese Encephalitis Virus, Yellow Fever Virus, a poxvirus, a Dengue virus, a papillomavirus, a togavirus, a flavivirus, an intracellular bacterium, Mycobacterium, Listeria, Brucella, Bartonella, Bordetella, Pseudomonas, Yersinia, Vibrio, Salmonella, Streptococcus, Staphylococcus, Candida, Aspergillus, Cryptococcus, Plasmodium, Trypanosoma, Leishmania, a gastrointestinal nematode, a helminth, Cryptosporidium, Toxoplasma, Pneumocystis, Schistosoma, or Strongyloides stercoralis.
2 . The method of claim 1 wherein the compound has the structure
wherein, hydrogen atoms at the 5 (if present), 8, 9 and 14 positions respectively in the α,α,α,α, α,α,α,β, α,α,β,α, α,β,α,α, α,α,β,β, α,β,α,β, α,β,β,α or α,β,β,β configurations.
3 . The method of claim 2 wherein hydrogen atoms at the 5 (if present), 8, 9 and 14 positions respectively are in the α,β,α,α configurations.
4 . The method of claim 1 wherein
(1) R 3 is a halogen and R 1 , R 2 , and one or both R 4 independently are —OH, —OR PR , an ether an ester having the structure steroid-O—C(O)-organic moiety, carbonate, carbamate having the structure steroid-O—C(O)—NR PR -organic moiety, or an amino acid ester or peptide having the structure (A) R 32 —NH—{[C(R 29 )(R 30 )] b —C(O)—N(R 31 )} f —[C(R 29 )(R 30 )] a —C(O)—O-steroid, (B) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} g —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—O—steroid, or (C) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} e —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—C(O)—O-steroid, where each R 29 , R 30 and R 31 is independently selected and each R 29 independently is —H or a C1-20 organic moiety, each R 30 independently is the side chain of an amino acid, each R 31 is —H or a protecting group, R 32 and R 33 independently are —H, a protecting group, an ester or an amide where each atom or group is independently chosen, a, b, c and d independently are 1, 2, 3, 4 or 5, and e, f and g independently are an integer from 0 to 1000, or
(2) R 1 , R 2 , R 3 and one or both R 4 independently are —OH, —OR PR , an ether, an ester having the structure steroid-O—C(O)-organic moiety, carbonate, carbamate having the structure steroid-O—C(O)—NR PR -organic moiety or an amino acid or peptide having the structure (A) R 32 —NH—{[C(R 29 )(R 30 )] b —C(O)—N(R 31 )} f -[C(R 29 )(R 30 )] a —C(O)—O-steroid, (B) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N (R 31 )} g —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—O-steroid, or (C) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} e —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—C(O)—O-steroid, or
(3) R 1 is −H and R 2 , R 3 and one or both R 4 are not —H, provided that the compound is not 7α,17α-methyl-16-methylene-17β-hydroxy-19-norandrost-4-ene, 7α-methyl-16-methylene-17β-hydroxy-17α-ethynyl-19-norandrost-4-ene or 7α-methyl-16-methylene-17-oxo-19-norandrost-4-ene or an ester or ether of any of these compounds, or
(4) R 1 is —CN, ═CH 2 , acyl, thioacyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, ester having the structure steroid-C(O)—O-organic moiety, thioester having the structure steroid-C(S)—O-organic moiety or thioacetal having the structure steroid-C(O)—S-organic moiety, and R 3 and one or both R 4 are not —H, provided that R 1 is not optionally substituted phenyl and provided that if R 1 is —C(O)—OCH 3 , then R 4 is not —CH 3 or —C(O)—CH 3 , or
(5) R 1 is a halogen and R 3 and one or both R 4 are not —H, provided that either R 3 is —OH, —OR PR , an ether, an ester having the structure steroid-O—C(O)-organic moiety, carbonate (O—C(O)—O—), carbamate, a halogen, —NH 2 , —N(R PR ) 2 , —NO 2 , —N 3 , ═NOH, ═NOC(O)CH 3 , an amide, —SH, —SR PR , ═S, thioether, thioacetal —CN, acyl, thioacyl, or an amino acid or peptide having the structure (A) R 32 —NH—{[C(R 29 )(R 30 )] b —C(O)—N(R 31 )} f —[C(R 29 )(R 30 )] a —C(O)—O-steroid, (B) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} g —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—O-steroid, or (C) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} e —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—C(O)—O-steroid, or one or both R 4 independently are —OH, —OR PR , an ether, an ester having the structure steroid-O—C(O)-organic moiety, carbonate, carbamate, a halogen, —NH 2 , —N(R PR ) 2 , —NO 2 , —N 3 , ═NOH, ═NOC(O)CH 3 , amide having the structure steroid-NR PR —C(O)-organic moiety, —SH, —SR PR , ═S, thioether, thioacetal having the structure steroid-S—C(O)-organic moiety, —CN, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, ester having the structure steroid-O—C(O)-organic moiety, thioester having the structure steroid-O—C(S)-organic moiety, thioacetal having the structure steroid-S—C(O)-organic moiety, or an amino acid or peptide having the structure (A) R 32 —NH—{[C(R 29 )(R 30 )] b —C(O)—N(R 31 )} f —[C(R 29 )(R 30 )] a —C(O)—O-steroid, (B) R 33 —O-{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} g —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—O-steroid, or (C) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} e —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—C(O)—O-steroid, or
(6) R 1 is a halogen, —NH 2 , —N(R PR ) 2 , —NO 2 , ═NOH, ═NOC(O)CH 3 , amide having the structure steroid-NR PR —C(O)-organic moiety, carbamate having the structure steroid-NR PR —C(O)—O-organic moiety, —SH, —SR PR , ═S, thioether, thioacetal having the structure steroid-S—C(O)-organic moiety, —CN, ═CH 2 , acyl, thioacyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, ester having the structure steroid-C(O)—O-organic moiety, thioester having the structure steroid-C(S)—O-organic moiety or thioacetal having the structure steroid-C(O)—S-organic moiety and R 2 , R 3 and one or both R 4 are not —H, or
(7) R 1 is a halogen, —NH 2 , —NO 2 , —N 3 , ═NOH, ═NOC(O)CH 3 , amide having the structure steroid-NR PR —C(O)-organic moiety, carbamate having the structure steroid-NR PR —C(O)—O-organic moiety, —SR PR , thioether, thioacetal having the structure steroid-S—C(O)-organic moiety, —CN, ═CH 2 , acyl, thioacyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, ester having the structure steroid-C(O)—O-organic moiety, thioester having the structure steroid-C(S)—O-organic moiety, or thioacetal having the structure steroid-C(O)—S-organic moiety and R 2 and one or both R 4 are not —H and R 9 is not —CH 2 —, provided that if one R 4 is —CH 2 CH 3 , then R 3 is not ═O, or
(8) R 1 is a halogen, —NH 2 , —N(R PR ) 2 , —NO 2 , —N 3 , ═NOH, ═NOC(O)CH 3 , amide having the structure steroid-NR PR —C(O)-organic moiety, carbamate having the structure steroid-NR PR —C(O)—O-organic moiety, —SR PR , thioether, thioacetal having the structure steroid-S—C(O)-organic moiety, —CN, ═CH 2 , acyl, thioacyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, ester having the structure steroid-C(O)—O-organic moiety, thioester having the structure steroid-C(S)—O-organic moiety, or thioacetal having the structure steroid-C(O)—S-organic moiety and R 2 and one or both R 4 are not —H and R 7 is not —CH 2 —, or
(9) R 1 is a halogen, —NH 2 , —N(R PR ) 2 , —NO 2 , —N 3 , ═NOH, ═NOC(O)CH 3 , amide having the structure steroid-NR PR —C(O)-organic moiety, carbamate having the structure steroid-NR PR —C(O)—O-organic moiety, —SR PR , thioether, thioacetal having the structure steroid-S—C(O)-organic moiety, —CN, ═CH 2 , acyl, thioacyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, ester having the structure steroid-C(O)—O-organic moiety, thioester having the structure steroid-C(S)—O-organic moiety, or thioacetal having the structure steroid-C(O)—S-organic moiety and R 2 and one or both R 4 are not —H, and R 6 is not —CH 3 , provided that R 1 is not fluorine if R 2 is ═O, one R 4 is —OH or —O—C(O)—CH 3 and R 6 is —CH 2 OH or —CH 2 O—C(O)—CH 3 , or
(10) R 1 is —H, R 2 and one or both R 4 are not —H and R 9 is not —CH 2 —, provided that R 9 is not —C(O)— or —CH(OH)— when R 2 is —OH in the α-configuration, both R 4 are —H and alkyl and a double bond is present at the 4-5 position, or
(11) R 1 is —H, R 2 is not —H and R 8 and R 9 are not —CH 2 —, or
(12) R 1 is a halogen, —NH 2 , —N(RPR) 2 , —NO 2 , —N 3 , ═NOH, ═NOC(O)CH 3 , amide having the structure steroid-NR PR —C(O)-organic moiety, carbamate having the structure steroid-NR PR —C(O)—O-organic moiety, —SH, —SR PR , ═S, thioether, thioacetal having the structure steroid-S—C(O)-organic moiety, —CN, ═CH 2 , acyl, thioacyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, ester having the structure steroid-C(O)—O-organic moiety, thioester having the structure steroid-C(S)—O-organic moiety, or thioacetal having the structure steroid-C(O)—S-organic moiety and R 3 and one or both R 4 are not —H, and R 6 is not —CH 3 , or
(13) the compound has the structure
wherein R 1 is —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 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer,
R 2 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer,
R 3 is —OH, —OR PR , —SH, —SRPR, ═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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, provided that the compound is not 3α-bromo-16α-methoxyandrost-5-ene-17-one, and
R 4 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, or
(14) the compound has the structure
wherein R 1 is —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 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer,
R 2 is —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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, and
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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, provided that the compound is not 3α-bromo-16α-methoxyandrost-5-ene-17-one, and
R 4 is —H, —OH, —OR PR , —SH, —SR PR , ═S, ═CH 2 , —N 3 , —NH 2 , —N(RPR) 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, or
(15) R 1 is a halogen, —NH 2 , —N(RPR) 2 , —NO 2 , —N 3 , ═NOH, amide having the structure steroid-NR PR —C(O)-organic moiety, carbamate having the structure steroid-NR PR —C(O)—O-organic moiety, —SR PR , thioether, thioacetal having the structure steroid-S—C(O)-organic moiety, —CN, ═CH 2 , acyl, thioacyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, ester having the structure steroid-C(O)—O-organic moiety, thioester having the structure steroid-C(S)—O-organic moiety, or thioacetal having the structure steroid-C(O)—S-organic moiety and R 2 , one or both R 4 and R 7 are not —H or —CH 2 —, provided that if R 1 is —NH 2 or —N(R PR ) 2 , then R 2 is not methyl, or
(16) R 1 is —H and R 3 , one or both R 4 are not —H and R 5 is not —CH 2 —, or
(17) R 1 is —H and R 3 , one or both R 4 are not —H and R 9 is not —CH 2 —, or
(18) R 1 is —H and R 2 , one or both R 4 are not —H and R 8 is not —CH 2 —, or
(19) R 1 is a halogen, R 2 and R 8 are not —H or —CH 2 — and one or both R 4 independently are —OR PR , ether, an ester having the structure steroid-O—C(O)-organic moiety, carbonate (O—C(O)—O—), carbamate having the structure steroid-O—C(O)—NR PR -organic moiety, optionally substituted monosaccharide, optionally substituted oligosaccharide, a nucleoside, a nucleotide, an oligonucleotide, a polymer, or an amino acid or peptide having the structure (A) R 32 —NH—{[C(R 29 )(R 30 )] b —C(O)—N(R 31 )} f —[C(R 29 )(R 30 )] a —C(O)—O-steroid, (B) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} g —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—O-steroid, or (C) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} e —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—C(O)—O-steroid.
5 . The method of claim 4 wherein hydrogen atoms at the 5 (if present), 8, 9 and 14 positions respectively are in the α,β,α,α configurations.
6 . The method of claim 1 wherein the compound has the structure
wherein, R 5 and R 6 independently are —CH 3 , —H or —CH 2 OH, R 7 , R 8 and R 9 independently are —CH 2 —, —O—, —NH— or —S—, R 1 , R 2 , R 3 and R 4 respectively are in the β,β,α,β, α,β,α,β, β,α,α,β, β,β,β,β, or β,β,α,α configurations and the compound's structure is designated by numbers assigned to R 1 , R 2 , R 3 and R 4 according to the convention, R 1 .R 2 .R 3 .R 4 , wherein the structures for R 1 , R 2 , R 3 and R 4 are designated by numbers respectively and, for R 1 , structure 1 is —OH, structure 3 is —SH, structure 4 is ═S, structure 5 is —OCH 3 , structure 6 is —O—S(O)(O)—O—Na + , structure 7 is —O—S(O)(O)—OC 2 H 5 , structure 8 is —CH 3 , structure 9 is —H, and structure 10 is —OC(O)C(CH 3 ) 3 , and
for R 2 , structure 1 is —H, structure 2 is —OH, structure 3 is ═O, structure 4 is —CH 3 , structure 5 is —OCH 3 , structure 6 is -OC 2 H 5 , structure 7 is —OCH 2 CH 2 CH 3 , structure 8 is —OCH 2 CH 2 CH 2 CH 3 , structure 9 is —Cl, and structure 10 is —Br, and
for R 3 , structure 1 is —Br, structure 2 is —Cl, structure 3 is —I, structure 4 is —F, structure 5 is —H, structure 6 is —OH, structure 7 is =O, structure 8 is —OC(O)CH 3 , structure 9 is —OC(O)CH 2 CH 3 , and structure 10 is —OC(O)CH 2 CH 2 CH 3 , and
for R 4 , structure 1 is ═O, structure 2 is —OH, structure 3 is —H, structure 4 is —F, structure 5 is —Cl, structure 6 is —Br, structure 7 is —I, structure 8 is —OC(O)CH 3 , structure 9 is —OC(O)CH 2 CH 3 , and structure 10 is —OC(O)CH 2 CH 2 CH 3 , wherein the compound is 1.1.1.1, 1.1.1.2, 1.1.1.3, 1.1.1.4, 1.1.1.5, 1.1.1.6, 1.1.1.7, 1.1.1.8, 1.1.1.9, 1.1.1.10, 1.1.2.1, 1.1.2.2, 1.1.2.3, 1.1.2.4, 1.1.2.5, 1.1.2.6, 1.1.2.7, 1.1.2.8, 1.1.2.9, 1.1.2.10, 1.1.3.1, 1.1.3.2, 1.1.3.3, 1.1.3.4, 1.1.3.5, 1.1.3.6, 1.1.3.7, 1.1.3.8, 1.1.3.9, 1.1.3.10, 1.1.4.1, 1.1.4.2, 1.1.4.3, 1.1.4.4, 1.1.4.5, 1.1.4.6, 1.1.4.7, 1.1.4.8, 1.1.4.9, 1.1.4.10, 1.1.5.1, 1.1.5.2, 1.1.5.3, 1.1.5.4, 1.1.5.5, 1.1.5.6, 1.1.5.7, 1.1.5.8, 1.1.5.9, 1.1.5.10, 1.1.6.1, 1.1.6.2, 1.1.6.3, 1.1.6.4, 1.1.6.5, 1.1.6.6, 1.1.6.7, 1.1.6.8, 1.1.6.9,1.1.6.10, 1.1.7.1, 1.1.7.2, 1.1.7.3, 1.1.7.4, 1.1.7.5, 1.1.7.6, 1.1.7.7, 1.1.7.8, 1.1.7.9, 1.1.7.10, 1.1.8.1, 1.1.8.2, 1.1.8.3, 1.1.8.4, 1.1.8.5, 1.1.8.6, 1.1.8.7, 1.1.8.8, 1.1.8.9, 1.1.8.10, 1.1.9.1, 1.1.9.2, 1.1.9.3, 1.1.9.4, 1.1.9.5, 1.1.9.6, 1.1.9.7, 1.1.9.8, 1.1.9.9, 1.1.9.10, 1.1.10.1, 1.1.10.2, 1.1.10.3, 1.1.10.4, 1.1.10.5, 1.1.10.6, 1.1.10.7, 1.1.10.8, 1.1.10.9, 1.1.10.10, 1.2.1.1, 1.2.1.2, 1.2.1.3, 1.2.1.4, 1.2.1.5, 1.2.1.6, 1.2.1.7, 1.2.1.8, 1.2.1.9, 1.2.1.10, 1.2.2.1, 1.2.2.2, 1.2.2.3, 1.2.2.4, 1.2.2.5, 1.2.2.6, 1.2.2.7, 1.2.2.8, 1.2.2.9, 1.2.2.10, 1.2.3.1, 1.2.3.2, 1.2.3.3, 1.2.3.4, 1.2.3.5, 1.2.3.6, 1.2.3.7, 1.2.3.8, 1.2.3.9, 1.2.3.10, 1.2.4.1, 1.2.4.2, 1.2.4.3, 1.2.4.4, 1.2.4.5, 1.2.4.6, 1.2.4.7, 1.2.4.8, 1.2.4.9, 1.2.4.10, 1.2.5.1, 1.2.5.2, 1.2.5.3, 1.2.5.4, 1.2.5.5, 1.2.5.6, 1.2.5.7, 1.2.5.8, 1.2.5.9, 1.2.5.10, 1.2.6.1, 1.2.6.2, 1.2.6.3, 1.2.6.4, 1.2.6.5, 1.2.6.6, 1.2.6.7, 1.2.6.8, 1.2.6.9, 1.2.6.10, 1.2.7.1, 1.2.7.2, 1.2.7.3, 1.2.7.4, 1.2.7.5, 1.2.7.6, 1.2.7.7, 1.2.7.8, 1.2.7.9, 1.2.7.10, 1.2.8.1, 1.2.8.2, 1.2.8.3, 1.2.8.4, 1.2.8.5, 1.2.8.6, 1.2.8.7, 1.2.8.8, 1.2.8.9, 1.2.8.10, 1.2.9.1, 1.2.9.2, 1.2.9.3, 1.2.9.4, 1.2.9.5, 1.2.9.6, 1.2.9.7, 1.2.9.8, 1.2.9.9, 1.2.9.10, 1.2.10.1, 1.2.10.2, 1.2.10.3, 1.2.10.4, 1.2.10.5, 1.2.10.6, 1.2.10.7, 1.2.10.8, 1.2.10.9, 1.2.10.10, 1.3.1.1, 1.3.1.2, 1.3.1.3, 1.3.1.4, 1.3.1.5, 1.3.1.6, 1.3.1.7, 1.3.1.8, 1.3.1.9, 1.3.1.10, 1.3.2.1, 1.3.2.2, 1.3.2.3, 1.3.2.4, 1.3.2.5, 1.3.2.6, 1.3.2.7, 1.3.2.8, 1.3.2.9, 1.3.2.10, 1.3.3.1, 1.3.3.2, 1.3.3.3, 1.3.3.4, 1.3.3.5, 1.3.3.6, 1.3.3.7, 1.3.3.8, 1.3.3.9, 1.3.3.10, 1.3.4.1, 1.3.4.2, 1.3.4.3, 1.3.4.4, 1.3.4.5, 1.3.4.6, 1.3.4.7, 1.3.4.8, 1.3.4.9, 1.3.4.10, 1.3.5.1, 1.3.5.2, 1.3.5.3, 1.3.5.4, 1.3.5.5, 1.3.5.6, 1.3.5.7, 1.3.5.8, 1.3.5.9, 1.3.5.10, 1.3.6.1, 1.3.6.2, 1.3.6.3, 1.3.6.4, 1.3.6.5, 1.3.6.6, 1.3.6.7, 1.3.6.8, 1.3.6.9, 1.3.6.10, 1.3.7.1, 1.3.7.2, 1.3.7.3, 1.3.7.4, 1.3.7.5, 1.3.7.6, 1.3.7.7, 1.3.7.8, 1.3.7.9, 1.3.7.10, 1.3.8.1, 1.3.8.2, 1.3.8.3, 1.3.8.4, 1.3.8.5, 1.3.8.6, 1.3.8.7, 1.3.8.8, 1.3.8.9, 1.3.8.10, 1.3.9.1, 1.3.9.2, 1.3.9.3, 1.3.9.4, 1.3.9.5, 1.3.9.6, 1.3.9.7, 1.3.9.8, 1.3.9.9, 1.3.9.10, 1.3.10.1, 1.3.10.2, 1.3.10.3, 1.3.10.4, 1.3.10.5, 1.3.10.6, 1.3.10.7, 1.3.10.8, 1.3.10.9, 1.3.10.10, 1.4.1.1, 1.4.1.2, 1.4.1.3, 1.4.1.4, 1.4.1.5, 1.4.1.6, 1.4.1.7, 1.4.1.8, 1.4.1.9, 1.4.1.10, 1.4.2.1, 1.4.2.2, 1.4.2.3, 1.4.2.4, 1.4.2.5, 1.4.2.6, 1.4.2.7, 1.4.2.8, 1.4.2.9, 1.4.2.10, 1.4.3.1, 1.4.3.2, 1.4.3.3, 1.4.3.4, 1.4.3.5, 1.4.3.6, 1.4.3.7, 1.4.3.8, 1.4.3.9, 1.4.3.10, 1.4.4.1, 1.4.4.2, 1.4.4.3, 1.4.4.4, 1.4.4.5, 1.4.4.6, 1.4.4.7, 1.4.4.8, 1.4.4.9, 1.4.4.10, 1.4.5.1, 1.4.5.2, 1.4.5.3, 1.4.5.4, 1.4.5.5, 1.4.5.6, 1.4.5.7, 1.4.5.8, 1.4.5.9, 1.4.5.10, 1.4.6.1, 1.4.6.2, 1.4.6.3, 1.4.6.4, 1.4.6.5, 1.4.6.6, 1.4.6.7, 1.4.6.8, 1.4.6.9, 1.4.6.10, 1.4.7.1, 1.4.7.2, 1.4.7.3, 1.4.7.4, 1.4.7.5, 1.4.7.6, 1.4.7.7, 1.4.7.8, 1.4.7.9, 1.4.7.10, 1.4.8.1, 1.4.8.2, 1.4.8.3, 1.4.8.4, 1.4.8.5, 1.4.8.6, 1.4.8.7, 1.4.8.8, 1.4.8.9, 1.4.8.10, 1.4.9.1, 1.4.9.2, 1.4.9.3, 1.4.9.4, 1.4.9.5, 1.4.9.6, 1.4.9.7, 1.4.9.8, 1.4.9.9, 1.4.9.10, 1.4.10.1, 1.4.10.2, 1.4.10.3, 1.4.10.4, 1.4.10.5, 1.4.10.6, 1.4.10.7, 1.4.10.8, 1.4.10.9, 1.4.10.10, 1.5.1.1, 1.5.1.2, 1.5.1.3, 1.5.1.4, 1.5.1.5, 1.5.1.6, 1.5.1.7, 1.5.1.8, 1.5.1.9, 1.5.1.10, 1.5.2.1, 1.5.2.2, 1.5.2.3, 1.5.2.4, 1.5.2.5, 1.5.2.6, 1.5.2.7, 1.5.2.8, 1.5.2.9, 1.5.2.10, 1.5.3.1, 1.5.3.2, 1.5.3.3, 1.5.3.4, 1.5.3.5, 1.5.3.6, 1.5.3.7, 1.5.3.8, 1.5.3.9, 1.5.3.10, 1.5.4.1, 1.5.4.2, 1.5.4.3, 1.5.4.4, 1.5.4.5, 1.5.4.6, 1.5.4.7, 1.5.4.8, 1.5.4.9, 1.5.4.10, 1.5.5.1, 1.5.5.2, 1.5.5.3, 1.5.5.4, 1.5.5.5, 1.5.5.6, 1.5.5.7, 1.5.5.8, 1.5.5.9, 1.5.5.10, 1.5.6.1, 1.5.6.2, 1.5.6.3, 1.5.6.4, 1.5.6.5, 1.5.6.6, 1.5.6.7, 1.5.6.8, 1.5.6.9, 1.5.6.10, 1.5.7.1, 1.5.7.2, 1.5.7.3, 1.5.7.4, 1.5.7.5, 1.5.7.6, 1.5.7.7, 1.5.7.8, 1.5.7.9, 1.5.7.10, 1.5.8.1, 1.5.8.2, 1.5.8.3, 1.5.8.4, 1.5.8.5, 1.5.8.6, 1.5.8.7, 1.5.8.8, 1.5.8.9, 1.5.8.10, 1.5.9.1, 1.5.9.2, 1.5.9.3, 1.5.9.4, 1.5.9.5, 1.5.9.6, 1.5.9.7, 1.5.9.8, 1.5.9.9, 1.5.9.10, 1.5.10.1, 1.5.10.2, 1.5.10.3, 1.5.10.4, 1.5.10.5, 1.5.10.6, 1.5.10.7, 1.5.10.8, 1.5.10.9, 1.5.10.10, 1.6.1.1, 1.6.1.2, 1.6.1.3, 1.6.1.4, 1.6.1.5, 1.6.1.6, 1.6.1.7, 1.6.1.8, 1.6.1.9, 1.6.1.10, 1.6.2.1, 1.6.2.2, 1.6.2.3, 1.6.2.4, 1.6.2.5, 1.6.2.6, 1.6.2.7, 1.6.2.8, 1.6.2.9, 1.6.2.10, 1.6.3.1, 1.6.3.2, 1.6.3.3, 1.6.3.4, 1.6.3.5, 1.6.3.6, 1.6.3.7, 1.6.3.8, 1.6.3.9, 1.6.3.10, 1.6.4.1, 1.6.4.2, 1.6.4.3, 1.6.4.4, 1.6.4.5, 1.6.4.6, 1.6.4.7, 1.6.4.8, 1.6.4.9, 1.6.4.10, 1.6.5.1, 1.6.5.2, 1.6.5.3, 1.6.5.4, 1.6.5.5, 1.6.5.6, 1.6.5.7, 1.6.5.8, 1.6.5.9, 1.6.5.10, 1.6.6.1, 1.6.6.2, 1.6.6.3, 1.6.6.4, 1.6.6.5, 1.6.6.6, 1.6.6.7, 1.6.6.8, 1.6.6.9, 1.6.6.10, 1.6.7.1, 1.6.7.2, 1.6.7.3, 1.6.7.4, 1.6.7.5, 1.6.7.6, 1.6.7.7, 1.6.7.8, 1.6.7.9, 1.6.7.10, 1.6.8.1, 1.6.8.2, 1.6.8.3, 1.6.8.4, 1.6.8.5, 1.6.8.6, 1.6.8.7, 1.6.8.8, 1.6.8.9, 1.6.8.10, 1.6.9.1, 1.6.9.2, 1.6.9.3, 1.6.9.4, 1.6.9.5, 1.6.9.6, 1.6.9.7, 1.6.9.8, 1.6.9.9, 1.6.9.10, 1.6.10.1, 1.6.10.2, 1.6.10.3, 1.6.10.4, 1.6.10.5, 1.6.10.6, 1.6.10.7, 1.6.10.8, 1.6.10.9, 1.6.10.10, 1.7.1.1, 1.7.1.2, 1.7.1.3, 1.7.1.4, 1.7.1.5, 1.7.1.6, 1.7.1.7, 1.7.1.8, 1.7.1.9, 1.7.1.10, 1.7.2.1, 1.7.2.2, 1.7.2.3, 1.7.2.4, 1.7.2.5, 1.7.2.6, 1.7.2.7, 1.7.2.8, 1.7.2.9, 1.7.2.10, 1.7.3.1, 1.7.3.2, 1.7.3.3, 1.7.3.4, 1.7.3.5, 1.7.3.6, 1.7.3.7, 1.7.3.8, 1.7.3.9, 1.7.3.10, 1.7.4.1, 1.7.4.2, 1.7.4.3, 1.7.4.4, 1.7.4.5, 1.7.4.6, 1.7.4.7, 1.7.4.8, 1.7.4.9, 1.7.4.10, 1.7.5.1, 1.7.5.2, 1.7.5.3, 1.7.5.4, 1.7.5.5, 1.7.5.6, 1.7.5.7, 1.7.5.8, 1.7.5.9, 1.7.5.10, 1.7.6.1, 1.7.6.2, 1.7.6.3, 1.7.6.4, 1.7.6.5, 1.7.6.6, 1.7.6.7, 1.7.6.8, 1.7.6.9, 1.7.6.10, 1.7.7.1, 1.7.7.2, 1.7.7.3, 1.7.7.4, 1.7.7.5, 1.7.7.6, 1.7.7.7, 1.7.7.8, 1.7.7.9, 1.7.7.10, 1.7.8.1, 1.7.8.2, 1.7.8.3, 1.7.8.4, 1.7.8.5, 1.7.8.6, 1.7.8.7, 1.7.8.8, 1.7.8.9, 1.7.8.10, 1.7.9.1, 1.7.9.2, 1.7.9.3, 1.7.9.4, 1.7.9.5, 1.7.9.6, 1.7.9.7, 1.7.9.8, 1.7.9.9, 1.7.9.10, 1.7.10.1, 1.7.10.2, 1.7.10.3, 1.7.10.4, 1.7.10.5, 1.7.10.6, 1.7.10.7, 1.7.10.8, 1.7.10.9, 1.7.10.10, 1.8.1.1, 1.8.1.2, 1.8.1.3, 1.8.1.4, 1.8.1.5, 1.8.1.6, 1.8.1.7, 1.8.1.8, 1.8.1.9, 1.8.1.10, 1.8.2.1, 1.8.2.2, 1.8.2.3, 1.8.2.4, 1.8.2.5, 1.8.2.6, 1.8.2.7, 1.8.2.8, 1.8.2.9, 1.8.2.10, 1.8.3.1, 1.8.3.2, 1.8.3.3, 1.8.3.4, 1.8.3.5, 1.8.3.6, 1.8.3.7, 1.8.3.8, 1.8.3.9, 1.8.3.10, 1.8.4.1, 1.8.4.2, 1.8.4.3, 1.8.4.4, 1.8.4.5, 1.8.4.6, 1.8.4.7, 1.8.4.8, 1.8.4.9, 1.8.4.10, 1.8.5.1, 1.8.5.2, 1.8.5.3, 1.8.5.4, 1.8.5.5, 1.8.5.6, 1.8.5.7, 1.8.5.8, 1.8.5.9, 1.8.5.10, 1.8.6.1, 1.8.6.2, 1.8.6.3, 1.8.6.4, 1.8.6.5, 1.8.6.6, 1.8.6.7, 1.8.6.8, 1.8.6.9, 1.8.6.10, 1.8.7.1, 1.8.7.2, 1.8.7.3, 1.8.7.4, 1.8.7.5, 1.8.7.6, 1.8.7.7, 1.8.7.8, 1.8.7.9, 1.8.7.10, 1.8.8.1, 1.8.8.2, 1.8.8.3, 1.8.8.4, 1.8.8.5, 1.8.8.6, 1.8.8.7, 1.8.8.8, 1.8.8.9, 1.8.8.10, 1.8.9.1, 1.8.9.2, 1.8.9.3, 1.8.9.4, 1.8.9.5, 1.8.9.6, 1.8.9.7, 1.8.9.8, 1.8.9.9, 1.8.9.10, 1.8.10.1, 1.8.10.2, 1.8.10.3, 1.8.10.4, 1.8.10.5, 1.8.10.6, 1.8.10.7, 1.8.10.8, 1.8.10.9, 1.8.10.10, 1.9.1.1, 1.9.1.2, 1.9.1.3, 1.9.1.4, 1.9.1.5, 1.9.1.6, 1.9.1.7, 1.9.1.8, 1.9.1.9, 1.9.1.10, 1.9.2.1, 1.9.2.2, 1.9.2.3, 1.9.2.4, 1.9.2.5, 1.9.2.6, 1.9.2.7, 1.9.2.8, 1.9.2.9, 1.9.2.10, 1.9.3.1, 1.9.3.2, 1.9.3.3, 1.9.3.4, 1.9.3.5, 1.9.3.6, 1.9.3.7, 1.9.3.8, 1.9.3.9, 1.9.3.10, 1.9.4.1, 1.9.4.2, 1.9.4.3, 1.9.4.4, 1.9.4.5, 1.9.4.6, 1.9.4.7, 1.9.4.8, 1.9.4.9, 1.9.4.10, 1.9.5.1, 1.9.5.2, 1.9.5.3, 1.9.5.4, 1.9.5.5, 1.9.5.6, 1.9.5.7, 1.9.5.8, 1.9.5.9, 1.9.5.10, 1.9.6.1, 1.9.6.2, 1.9.6.3, 1.9.6.4, 1.9.6.5, 1.9.6.6, 1.9.6.7, 1.9.6.8, 1.9.6.9, 1.9.6.10, 1.9.7.1, 1.9.7.2, 1.9.7.3, 1.9.7.4, 1.9.7.5, 1.9.7.6, 1.9.7.7, 1.9.7.8, 1.9.7.9, 1.9.7.10, 1.9.8.1, 1.9.8.2, 1.9.8.3, 1.9.8.4, 1.9.8.5, 1.9.8.6, 1.9.8.7, 1.9.8.8, 1.9.8.9, 1.9.8.10, 1.9.9.1, 1.9.9.2, 1.9.9.3, 1.9.9.4, 1.9.9.5, 1.9.9.6, 1.9.9.7, 1.9.9.8, 1.9.9.9, 1.9.9.10, 1.9.10.1, 1.9.10.2, 1.9.10.3, 1.9.10.4, 1.9.10.5, 1.9.10.6, 1.9.10.7, 1.9.10.8, 1.9.10.9, 1.9.10.10, 1.10.1.1, 1.10.1.2, 1.10.1.3, 1.10.1.4, 1.10.1.5, 1.10.1.6, 1.10.1.7, 1.10.1.8, 1.10.1.9, 1.10.1.10, 1.10.2.1, 1.10.2.2, 1.10.2.3, 1.10.2.4, 1.10.2.5, 1.10.2.6, 1.10.2.7, 1.10.2.8, 1.10.2.9, 1.10.2.10, 1.10.3.1, 1.10.3.2, 1.10.3.3, 1.10.3.4, 1.10.3.5, 1.10.3.6, 1.10.3.7, 1.10.3.8, 1.10.3.9, 1.10.3.10, 1.10.4.1, 1.10.4.2, 1.10.4.3, 1.10.4.4, 1.10.4.5, 1.10.4.6, 1.10.4.7, 1.10.4.8, 1.10.4.9, 1.10.4.10, 1.10.5.1, 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10.3.9.8, 10.3.9.9, 10.3.9.10, 10.3.10.1, 10.3.10.2, 10.3.10.3, 10.3.10.4, 10.3.10.5, 10.3.10.6, 10.3.10.7, 10.3.10.8, 10.3.10.9, 10.3.10.10, 10.4.1.1, 10.4.1.2, 10.4.1.3, 10.4.1.4, 10.4.1.5, 10.4.1.6, 10.4.1.7, 10.4.1.8, 10.4.1.9, 10.4.1.10, 10.4.2.1, 10.4.2.2, 10.4.2.3, 10.4.2.4, 10.4.2.5, 10.4.2.6, 10.4.2.7, 10.4.2.8, 10.4.2.9, 10.4.2.10, 10.4.3.1, 10.4.3.2, 10.4.3.3, 10.4.3.4, 10.4.3.5, 10.4.3.6, 10.4.3.7, 10.4.3.8, 10.4.3.9, 10.4.3.10, 10.4.4.1, 10.4.4.2, 10.4.4.3, 10.4.4.4, 10.4.4.5, 10.4.4.6, 10.4.4.7, 10.4.4.8, 10.4.4.9, 10.4.4.10, 10.4.5.1, 10.4.5.2, 10.4.5.3, 10.4.5.4, 10.4.5.5, 10.4.5.6, 10.4.5.7, 10.4.5.8, 10.4.5.9, 10.4.5.10, 10.4.6.1, 10.4.6.2, 10.4.6.3, 10.4.6.4, 10.4.6.5, 10.4.6.6, 10.4.6.7, 10.4.6.8, 10.4.6.9, 10.4.6.10, 10.4.7.1, 10.4.7.2, 10.4.7.3, 10.4.7.4, 10.4.7.5, 10.4.7.6, 10.4.7.7, 10.4.7.8, 10.4.7.9, 10.4.7.10, 10.4.8.1, 10.4.8.2, 10.4.8.3, 10.4.8.4, 10.4.8.5, 10.4.8.6, 10.4.8.7, 10.4.8.8, 10.4.8.9, 10.4.8.10, 10.4.9.1, 10.4.9.2, 10.4.9.3, 10.4.9.4, 10.4.9.5, 10.4.9.6, 10.4.9.7, 10.4.9.8, 10.4.9.9, 10.4.9.10, 10.4.10.1, 10.4.10.2, 10.4.10.3, 10.4.10.4, 10.4.10.5, 10.4.10.6, 10.4.10.7, 10.4.10.8, 10.4.10.9, 10.4.10.10, 10.5.1.1, 10.5.1.2, 10.5.1.3, 10.5.1.4, 10.5.1.5, 10.5.1.6, 10.5.1.7, 10.5.1.8, 10.5.1.9, 10.5.1.10, 10.5.2.1, 10.5.2.2, 10.5.2.3, 10.5.2.4, 10.5.2.5, 10.5.2.6, 10.5.2.7, 10.5.2.8, 10.5.2.9, 10.5.2.10, 10.5.3.1, 10.5.3.2, 10.5.3.3, 10.5.3.4, 10.5.3.5, 10.5.3.6, 10.5.3.7, 10.5.3.8, 10.5.3.9, 10.5.3.10, 10.5.4.1, 10.5.4.2, 10.5.4.3, 10.5.4.4, 10.5.4.5, 10.5.4.6, 10.5.4.7, 10.5.4.8, 10.5.4.9, 10.5.4.10, 10.5.5.1, 10.5.5.2, 10.5.5.3, 10.5.5.4, 10.5.5.5, 10.5.5.6, 10.5.5.7, 10.5.5.8, 10.5.5.9, 10.5.5.10, 10.5.6.1, 10.5.6.2, 10.5.6.3, 10.5.6.4, 10.5.6.5, 10.5.6.6, 10.5.6.7, 10.5.6.8, 10.5.6.9, 10.5.6.10, 10.5.7.1, 10.5.7.2, 10.5.7.3, 10.5.7.4, 10.5.7.5, 10.5.7.6, 10.5.7.7, 10.5.7.8, 10.5.7.9, 10.5.7.10, 10.5.8.1, 10.5.8.2, 10.5.8.3, 10.5.8.4, 10.5.8.5, 10.5.8.6, 10.5.8.7, 10.5.8.8, 10.5.8.9, 10.5.8.10, 10.5.9.1, 10.5.9.2, 10.5.9.3, 10.5.9.4, 10.5.9.5, 10.5.9.6, 10.5.9.7, 10.5.9.8, 10.5.9.9, 10.5.9.10, 10.5.10.1, 10.5.10.2, 10.5.10.3, 10.5.10.4, 10.5.10.5, 10.5.10.6, 10.5.10.7, 10.5.10.8, 10.5.10.9, 10.5.10.10, 10.6.1.1, 10.6.1.2, 10.6.1.3, 10.6.1.4, 10.6.1.5, 10.6.1.6, 10.6.1.7, 10.6.1.8, 10.6.1.9, 10.6.1.10, 10.6.2.1, 10.6.2.2, 10.6.2.3, 10.6.2.4, 10.6.2.5, 10.6.2.6, 10.6.2.7, 10.6.2.8, 10.6.2.9, 10.6.2.10, 10.6.3.1, 10.6.3.2, 10.6.3.3, 10.6.3.4, 10.6.3.5, 10.6.3.6, 10.6.3.7, 10.6.3.8, 10.6.3.9, 10.6.3.10, 10.6.4.1, 10.6.4.2, 10.6.4.3, 10.6.4.4, 10.6.4.5, 10.6.4.6, 10.6.4.7, 10.6.4.8, 10.6.4.9, 10.6.4.10, 1 0.6.5.1, 10.6.5.2, 1 0.6.5.3, 10.6.5.4, 10.6.5.5, 10.6.5.6, 10.6.5.7, 10.6.5.8, 10.6.5.9, 10.6.5.10, 10.6.6.1, 10.6.6.2, 10.6.6.3, 10.6.6.4, 10.6.6.5, 10.6.6.6, 10.6.6.7, 10.6.6.8, 10.6.6.9, 10.6.6.10, 10.6.7.1, 10.6.7.2, 10.6.7.3, 10.6.7.4, 10.6.7.5, 10.6.7.6, 10.6.7.7, 10.6.7.8, 10.6.7.9, 10.6.7.10, 10.6.8.1, 10.6.8.2, 10.6.8.3, 10.6.8.4, 10.6.8.5, 10.6.8.6, 10.6.8.7, 10.6.8.8, 10.6.8.9, 10.6.8.10, 10.6.9.1, 10.6.9.2, 10.6.9.3, 10.6.9.4, 10.6.9.5, 10.6.9.6, 10.6.9.7, 10.6.9.8, 10.6.9.9, 10.6.9.10, 10.6.10.1, 10.6.10.2, 10.6.10.3, 10.6.10.4, 10.6.10.5, 10.6.10.6, 10.6.10.7, 10.6.10.8, 10.6.10.9, 10.6.10.10, 10.7.1.1, 10.7.1.2, 10.7.1.3, 10.7.1.4, 10.7.1.5, 10.7.1.6, 10.7.1.7, 10.7.1.8, 10.7.1.9, 10.7.1.10, 10.7.2.1, 10.7.2.2, 10.7.2.3, 10.7.2.4, 10.7.2.5, 10.7.2.6, 10.7.2.7, 10.7.2.8, 10.7.2.9, 10.7.2.10, 10.7.3.1, 10.7.3.2, 10.7.3.3, 10.7.3.4, 10.7.3.5, 10.7.3.6, 10.7.3.7, 10.7.3.8, 10.7.3.9, 10.7.3.10, 10.7.4.1, 10.7.4.2, 10.7.4.3, 10.7.4.4, 10.7.4.5, 10.7.4.6, 10.7.4.7, 10.7.4.8, 10.7.4.9, 10.7.4.10, 10.7.5.1, 10.7.5.2, 10.7.5.3, 10.7.5.4, 10.7.5.5, 10.7.5.6, 10.7.5.7, 10.7.5.8, 10.7.5.9, 10.7.5.10, 10.7.6.1, 10.7.6.2, 10.7.6.3, 10.7.6.4, 10.7.6.5, 10.7.6.6, 10.7.6.7, 10.7.6.8, 10.7.6.9, 10.7.6.10, 10.7.7.1, 10.7.7.2, 10.7.7.3, 10.7.7.4, 10.7.7.5, 10.7.7.6, 10.7.7.7, 10.7.7.8, 10.7.7.9, 10.7.7.10, 10.7.8.1, 10.7.8.2, 10.7.8.3, 10.7.8.4, 10.7.8.5, 10.7.8.6, 10.7.8.7, 10.7.8.8, 10.7.8.9, 10.7.8.10, 10.7.9.1, 10.7.9.2, 10.7.9.3, 10.7.9.4, 10.7.9.5, 10.7.9.6, 10.7.9.7, 10.7.9.8, 10.7.9.9, 10.7.9.10, 10.7.10.1, 10.7.10.2, 10.7.10.3, 10.7.10.4, 10.7.10.5, 10.7.10.6, 10.7.10.7, 10.7.10.8, 10.7.10.9, 10.7.10.10, 10.8.1.1, 10.8.1.2, 10.8.1.3, 10.8.1.4, 10.8.1.5, 10.8.1.6, 10.8.1.7, 10.8.1.8, 10.8.1.9, 10.8.1.10, 10.8.2.1, 10.8.2.2, 10.8.2.3, 10.8.2.4, 10.8.2.5, 10.8.2.6, 10.8.2.7, 10.8.2.8, 10.8.2.9, 10.8.2.10, 10.8.3.1, 10.8.3.2, 10.8.3.3, 10.8.3.4, 10.8.3.5, 10.8.3.6, 10.8.3.7, 10.8.3.8, 10.8.3.9, 10.8.3.10, 10.8.4.1, 10.8.4.2, 10.8.4.3, 10.8.4.4, 10.8.4.5, 10.8.4.6, 10.8.4.7, 10.8.4.8, 10.8.4.9, 10.8.4.10, 10.8.5.1, 10.8.5.2, 10.8.5.3, 10.8.5.4, 10.8.5.5, 10.8.5.6, 10.8.5.7, 10.8.5.8, 10.8.5.9, 10.8.5.10, 10.8.6.1 10.8.6.2, 10.8.6.3, 10.8.6.4, 10.8.6.5, 10.8.6.6, 10.8.6.7, 10.8.6.8, 10.8.6.9, 10.8.6.10, 10.8.7.1, 10.8.7.2, 10.8.7.3, 10.8.7.4, 10.8.7.5, 10.8.7.6, 10.8.7.7, 10.8.7.8, 10.8.7.9, 10.8.7.10, 10.8.8.1, 10.8.8.2, 10.8.8.3, 10.8.8.4, 10.8.8.5, 10.8.8.6, 10.8.8.7, 10.8.8.8, 10.8.8.9, 10.8.8.10, 10.8.9.1, 10.8.9.2, 10.8.9.3, 10.8.9.4, 10.8.9.5, 10.8.9.6, 10.8.9.7, 10.8.9.8, 10.8.9.9, 10.8.9.10, 10.8.10.1, 10.8.10.2, 10.8.10.3, 10.8.10.4, 10.8.10.5, 10.8.10.6, 10.8.10.7, 10.8.10.8, 10.8.10.9, 10.8.10.10, 10.9.1.1, 10.9.1.2, 10.9.1.3, 10.9.1.4, 10.9.1.5, 10.9.1.6, 10.9.1.7, 10.9.1.8, 10.9.1.9, 10.9.1.10, 10.9.2.1, 10.9.2.2, 10.9.2.3, 10.9.2.4, 10.9.2.5, 10.9.2.6, 10.9.2.7, 10.9.2.8, 10.9.2.9, 10.9.2.10, 10.9.3.1, 10.9.3.2, 10.9.3.3, 10.9.3.4, 10.9.3.5, 10.9.3.6, 10.9.3.7, 10.9.3.8, 10.9.3.9, 10.9.3.10, 10.9.4.1, 10.9.4.2, 10.9.4.3, 10.9.4.4, 10.9.4.5, 10.9.4.6, 10.9.4.7, 10.9.4.8, 10.9.4.9, 10.9.4.10, 10.9.5.1, 10.9.5.2, 10.9.5.3, 10.9.5.4, 10.9.5.5, 10.9.5.6, 10.9.5.7, 10.9.5.8, 10.9.5.9, 10.9.5.10, 10.9.6.1, 10.9.6.2, 10.9.6.3, 10.9.6.4, 10.9.6.5, 10.9.6.6, 10.9.6.7, 10.9.6.8, 10.9.6.9, 10.9.6.10, 10.9.7.1, 10.9.7.2, 10.9.7.3, 10.9.7.4, 10.9.7.5, 10.9.7.6, 10.9.7.7, 10.9.7.8, 10.9.7.9, 10.9.7.10, 10.9.8.1, 10.9.8.2, 10.9.8.3, 10.9.8.4, 10.9.8.5, 10.9.8.6, 10.9.8.7, 10.9.8.8, 10.9.8.9, 10.9.8.10, 10.9.9.1, 10.9.9.2, 10.9.9.3, 10.9.9.4, 10.9.9.5, 10.9.9.6, 10.9.9.7, 10.9.9.8, 10.9.9.9, 10.9.9.10, 10.9.10.1, 10.9.10.2, 10.9.10.3, 10.9.10.4, 10.9.10.5, 10.9.10.6, 10.9.10.7, 10.9.10.8, 10.9.10.9, 10.9.10.10, 10.10.1.1, 10.10.1.2, 10.10.1.3, 10.10.1.4, 10.10.1.5, 10.10.1.6, 10.10.1.7, 10.10.1.8, 10.10.1.9, 10.10.1.10, 10.10.2.1, 10.10.2.2, 10.10.2.3, 10.10.2.4, 10.10.2.5, 10.10.2.6, 10.10.2.7, 10.10.2.8, 10.10.2.9, 10.10.2.10, 10.10.3.1, 10.10.3.2, 10.10.3.3, 10.10.3.4, 10.10.3.5, 10.10.3.6, 10.10.3.7, 10.10.3.8, 10.10.3.9, 10.10.3.10, 10.10.4.1, 10.10.4.2, 10.10.4.3, 10.10.4.4, 10.10.4.5, 10.10.4.6, 10.10.4.7, 10.10.4.8, 10.10.4.9, 10.10.4.10, 10.10.5.1, 10.10.5.2, 10.10.5.3, 10.10.5.4, 10.10.5.5, 10.10.5.6, 10.10.5.7, 10.10.5.8, 10.10.5.9, 10.10.5.10, 10.10.6.1, 10.10.6.2, 10.10.6.3, 10.10.6.4, 10.10.6.5, 10.10.6.6, 10.10.6.7, 10.10.6.8, 10.10.6.9, 10.10.6.10, 10.10.7.1, 10.10.7.2, 10.10.7.3, 10.10.7.4, 10.10.7.5, 10.10.7.6, 10.10.7.7, 10.10.7.8, 10.10.7.9, 10.10.7.10, 10.10.8.1, 10.10.8.2, 10.10.8.3, 10.10.8.4, 10.10.8.5, 10.10.8.6, 10.10.8.7, 10.10.8.8, 10.10.8.9, 10.10.8.10, 10.10.9.1, 10.10.9.2, 10.10.9.3, 10.10.9.4, 10.10.9.5, 10.10.9.6, 10.10.9.7, 10.10.9.8, 10.10.9.9, 10.10.9.10, 10.10.10.1, 10.10.10.2, 10.10.10.3, 10.10.10.4, 10.10.10.5, 10.10.10.6, 10.10.10.7, 10.10.10.8, 10.10.10.9 or 10.10.10.10.
7 . The method of claim 6 wherein R 1 , R 2 , R 3 and R 4 respectively are in the β,β,α,β configurations.
8 . The method of claim 6 wherein R 1 , R 2 , R 3 and R 4 respectively are in the β,β,β,β configurations.
9 . The method of claim 6 wherein R 1 , R 2 , R 3 and R 4 respectively are in the α,β,α,β configurations.
10 . The method of claim 6 wherein no double bond is present at the 1-2 or 5-6 positions, R 1 , R 2 , R 3 and R 4 respectively are in the β,β,α,β configurations, R 5 and R 6 are —CH 3 and R 7 , R 8 and R 9 are —CH 2 —.
11 . The method of claim 6 wherein no double bond is present at the 1-2 position, a double bond is present at the 5-6 position, R 1 , R 2 , R 3 and R 4 respectively are in the β,β,α,β configurations, R 5 and R 6 are —CH 3 and R 7 , R 8 and R 9 are —CH 2 —.
12 . The method of claim 6 wherein no double bond is present at the 1-2 position, a double bond is present at the 5-6 position, R 1 , R 2 , R 3 and R 4 respectively are in the β,α,α,β configurations, R 5 and R 6 are —CH 3 and R 7 , R 8 and R 9 are —CH 2 —.
13 . The method of claim 6 wherein no double bond is present at the 5-6 position, a double bond is present at the 1-2 position, R 1 , R 2 , R 3 and R 4 respectively are in the α,β,α,β configurations, R 5 and R 6 are —CH 3 and R 7 , R 8 and R 9 are —CH 2 —.
12 . The method of claim 6 wherein R 8 is —O— or —NH— and R 7 and R 9 are —CH 2 —.
13 . The method of claim 6 wherein R 9 is —O— or —NH— and R 7 and R 8 are —CH 2 —.
14 . The method of claim 6 wherein R 7 , R 8 and R 9 are —CH 2 — and no double bond is present at the 1-2 or 5-6 positions.
15 . The method of claim 6 wherein R 7 , R 8 and R 9 are —CH 2 —, no double bond is present at the 1-2 position and a double bond is present at the 5-6 position.
16 . The method of claim 6 wherein R 7 , R 8 and R 9 are —CH 2 —, a double bond is present at the 1-2 position and no double bond is present at the 5-6 position.
17 . The method of claim 6 wherein the compound is 16β-bromo-3β-hydroxy-5α-androstan-17-one, 16α-bromo-3β-hydroxy-5α-androstan-17-one, 3β,16β-dihydroxy-5α-androstan-17-one, 3β,16β-dihydroxy-5α-androstan-17-one, 3β,16α,17β-trihydroxy-5α-androstane, 3β,16β,17β-trihydroxy-5α-androstane or 3α,16α,17β-trihydroxy-5α-androstane.
18 . The method of claim 6 wherein the compound is 3β-hydroxy-16α-fluoro-5α-androstan-17-one, 16α-fluoroandrost-5-ene-17-one, 7β-hydroxy-16α-fluoroandrost-5-ene-17-one, 7α-hydroxy-16α-fluoroandrost-5-ene-17-one, 3α-hydroxy-16α-fluoroandrost-5-ene-17-one, 3α,17β-dihydroxy-16α-fluoroandrost-5-ene, 3α,7β,17β-trihydroxy-16α-fluoroandrost-5-ene, 3α,17β-dihydroxy-7-oxo-16α-fluoroandrost-5-ene, 7,17-dioxo-16α-fluoroandrost-5-ene or 17β-hydroxy-7-oxo-16α-fluoroandrost-5-ene.
19 . The method of claim 6 wherein the compound is 3β,17β-dihydroxyandrost-5-ene, 3β,7β,17β-trihydroxyandrost-5-ene, 3β,7β,17β-trihydroxy-16-oxoandrost-5-ene, 3β,7α,17β-trihydroxyandrost-5-ene, 3β,16α,17β-trihydroxyandrost-5-ene, 3β,17β-dihydroxy-7-oxoandrost-5-ene, 3β,7β,16α,17β-tetrahydroxyandrost-5-ene or 3β,7β,17β-trihydroxy-16α-bromoandrost-5-ene.
20 . The method of claim 17 wherein the compound is 16α-bromo-3β-hydroxy-5α-androstan-17-one.
21 . The method of claim 1 wherein the compound is 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate.
22 . The method of claim 19 wherein the compound is 3β,17β-dihydroxyandrost-5-ene.
23 . The method of claim 19 wherein the compound is 3β,7β,17β-trihydroxyandrost-5-ene.
24 . The method of claim 19 wherein the compound is 3α,17β-dihydroxy-16α-fluoroandrost-5-ene.
25 . The method of claim 17 wherein the compound is 16β-bromo-3β-hydroxy-5α-androstan-17-one.
26 . The method of claim 17 wherein the compound is 3β,16α-dihydroxy-5α-androstan-17-one or 3α,16α,17β-trihydroxy-5α-androstane.
27 . The method of claim 1 wherein the intermittent dosing protocol comprises: (a) administering the compound to the subject at least once per day for at least 2 days; (b) not administering the one or more formula 1 compounds to the subject for at least 1 day; (c) administering the one or more formula 1 compounds to the subject at least once per day for at least 2 days; and (d) optionally repeating steps (a), (b) and (c) at least once or variations of steps (a), (b) and (c) at least once.
28 . The method of claim 27 wherein step (c) comprises the same dosing period as step (a).
29 . The method of claim 28 wherein step (a) is administering the compound for about 3-24 days.
30 . The method of claim 28 wherein step (b) is not administering the compound for about 3-120 days.
31 . The method of claim 29 wherein step (b) is not administering the compound for about 3-120 days.
32 . The method of claim 29 wherein step (b) comprises not administering the compound for about 4-60 days.
33 . The method of claim 27 wherein step (b) comprises not administering the compound for about 4-60 days.
34 . The method of claim 31 wherein the compound is 16β-bromo-3β-hydroxy-5α-androstan-17-one, 16α-bromo-3β-hydroxy-5α-androstan-17-one, 3β,16α-dihydroxy-5α-androstan-17-one, 3β,16β-dihydroxy-5α-androstan-17-one, 3β,16α,17β-trihydroxy-5α-androstane, 3β,16β,17β-trihydroxy-5α-androstane, 3α,16α,17β-trihydroxy-5α-androstane, 16α-fluoro-3β-hydroxy-5α-androstan-17-one, 16α-fluoroandrost-5-ene-17-one, 7β-hydroxy-16α-fluoroandrost-5-ene-17-one, 7α-hydroxy-16α-fluoroandrost-5-ene-17-one, 3α-hydroxy-16α-fluoroandrost-5-ene-17-one, 3α,17β-dihydroxy-16α-fluoroandrost-5-ene, 3α,7β,17β-trihydroxy-16α-fluoroandrost-5-ene, 3β,17β-dihydroxyandrost-5-ene, 3β,7β,17β-trihydroxyandrost-5-ene, 3β,7α,17β-trihydroxyandrost-5-ene, 3β,16α,17β-trihydroxyandrost-5-ene, 3β,17β-dihydroxy-7-oxoandrost-5-ene, 3β,7β,16α,17β-tetrahydroxyandrost-5-ene or 3β,7β,17β-trihydroxy-16α-bromoandrost-5-ene.
35 . The method of claim 31 wherein the compound is 16β-bromo-3β-hydroxy-5α-androstan-17-one, 16α-bromo-3β-hydroxy-5α-androstan-17-one, 3β,16α-dihydroxy-5α-androstan-17-one, 3β,16β-dihydroxy-5α-androstan-17-one, 3β,16α,17β-trihydroxy-5α-androstane, 3β,16β,17β-trihydroxy-5α-androstane or 16α-fluoro-3β-hydroxy-5α-androstan-17-one.
36 . The method of claim 31 wherein the compound is 3β,17β-dihydroxyandrost-5-ene,3β,7β,17β-trihydroxyandrost-5-ene, 3β,7α,17β-trihydroxyandrost-5-ene, 3β,16α,17β-trihydroxyandrost-5-ene, 3β,17β-dihydroxy-7-oxoandrost-5-ene, 3β,7β,16α,17β-tetrahydroxyandrost-5-ene or 3β,7β,17β-trihydroxy-16α-bromoandrost-5-ene.
37 . The method of claim 35 wherein the compound is 16α-bromo-3β-hydroxy-5α-androstan-17-one.
38 . The method of claim 37 wherein the 16α-bromo-3β-hydroxy-5α-androstan-17-one comprises 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate.
39 . The method of claim 36 wherein the compound is 3β,7β,17β-dihydroxyandrost-5-ene.
40 . The method of claim 36 wherein the compound is 3β,7β,17 62 -trihydroxyandrost-5-ene.
41 . The method of claim 34 wherein the compound is 3α,17β-dihydroxy-16α-fluoroandrost-5-ene.
42 . The method of claim 35 wherein the compound is 16β-bromo-3β-hydroxy-5α-androstan-17-one.
43 . The method of claim 35 wherein the compound is 3β,16α-dihydroxy-5α-androstan-17-one.
44 . The method of claim 34 , wherein the subject has a pathogen infection.
45 . The method of claim 44 , wherein the pathogen infection is a viral infection.
46 . The method of claim 45 , wherein the viral infection is a retrovirus infection, optionally selected from the group consisting of a HIV-1 infection and a HIV-2 infection.
47 . The method of claim 45 where the infection is a hepatitis B virus infection, a hepatitis C virus infection, a poxvirus infection or a papillomavirus infection.
48 . The method of claim 44 , wherein the pathogen infection is a parasite infection.
49 . The method of claim 48 , wherein the parasite infection is a Plasmodium infection, a Trypanosoma infection, a Leishmania infection, a Schistosoma infection or a Cryptosporidium infection.
50 . The method of claim 44 , wherein the pathogen infection is a bacterial, fungal or yeast infection.
51 . The method of claim 50 , wherein the bacterial, fungal or yeast infection is an intracellular bacterium infection, a Mycobacterium infection, a Brucella infection, a Pseudomonas infection, a Yersinia infection, a Vibrio infection, a Salmonella infection, a Candida infection, an Aspergillus infection or a Cryptococcus infection.
52 . The method of claim 34 wherein the subject has a cancer or a precancer.
53 . The method of claim 52 wherein the cancer or precancer is a cancer or precancer arising in the throat, esophagus, stomach, intestine, colon, lung, or central nervous system.
54 . The method of claim 34 , wherein the subject has, or is subject to developing, an immunosuppression condition or an unwanted immune response either or both of which are associated with a chemotherapy, or radiation exposure.
55 . The method of claim 54 , wherein the chemotherapy or radiation exposure is a cyclosporin, cyclohexamide, mitomycin C, adriamycin, taxol, amphotericin B, cis-platin, a protease inhibitor, a nucleoside analog, a nucleotide analog or a corticosteroid treatment or γ-radiation therapy.
56 . The method of claim 34 , wherein the subject has a wound, osteoporosis, a bone fracture, a hemorrhage or a burn.
57 . The method of claim 34 , wherein the subject has a neurological disorder.
58 . The method of claim 57 , wherein the neurological disorder is AIDS associated dementia, Alzheimer's disease, Parkinson's disease, schizophrenia or multiple sclerosis.
59 . A method to administer a compound to a subject, wherein the method comprises intermittent administration of about 0.05 mg/kg to about 30 mg/kg per day of a compound to the subject, wherein the compound is 16β-bromo-3β-hydroxy-5α-androstan-17-one, 16α-bromo-3β-hydroxy-5α-androstan-17-one, 3β,16α-dihydroxy-5α-androstan-17-one, 3β,16β-dihydroxy-5α-androstan-17-one, 3β,16α,17β-trihydroxy-5α-androstane, 3β,16β,17β-trihydroxy-5α-androstane, 16α-fluoro-3β-hydroxy-5α-androstan-17-one, 16α-fluoroandrost-5-ene-17-one, 7β-hydroxy-16α-fluoroandrost-5-ene-17-one, 7α-hydroxy-16α-fluoroandrost-5-ene-17-one, 3α-hydroxy-16α-fluoroandrost-5-ene-17-one, 3α,17β-dihydroxy-16α-fluoroandrost-5-ene, 3α,7β,17β-trihydroxy-16α-fluoroandrost-5-ene, 3β,17β-dihydroxyandrost-5-ene, 3β,7β,17β-trihydroxyandrost-5-ene, 3β,7α,17β-trihydroxyandrost-5-ene, 3β,16α,17β-trihydroxyandrost-5-ene, 3β,17β-dihydroxy-7-oxoandrost-5-ene, 3β,7β,16β,17β-tetrahydroxyandrost-5-ene or 3β,7β,17β-trihydroxy-16α-bromoandrost-5-ene.
60 . The method of claim 59 wherein the subject is a human.
61 . The method of claim 59 wherein the intermittent dosing protocol comprises the steps of: (a) administering the compound(s) to the subject at least once per day for at least 2 days; (b) not administering the compound(s) to the subject for at least 1 day; (c) administering the compound(s) to the subject at least once per day for at least 2 days; and (d) optionally repeating steps (a), (b) and (c) at least once or variations of steps (a), (b) and (c) at least once, and wherein the subject is a human.
62 . The method of claim 61 wherein step (c) comprises the same dosing regimen as step (a).
63 . The method of claim 61 wherein step (a) is administering the compound for about 3-24 days.
64 . The method of claim 62 wherein step (a) is administering the compound for about 3-24 days.
65 . The method of claim 62 wherein step (b) is not administering the compound for about 3-120 days.
66 . The method of claim 63 wherein step (b) is not administering the compound for about 3-120 days.
67 . The method of claim 62 wherein step (b) comprises not administering the compound for about 4-60 days.
68 . The method of claim 63 wherein step (b) comprises not administering the compound for about 4-60 days.
69 . The method of claim 61 wherein the compound is 16α-bromo-3β-hydroxy-5α-androstan-17-one.
70 . The method of claim 69 wherein the 16α-bromo-3β-hydroxy-5α-androstan-17-one comprises 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate.
71 . The method of claim 66 wherein the compound is 16α-bromo-3β-hydroxy-5α-androstan-1 7-one.
72 . The method of claim 71 wherein the 16α-bromo-3β-hydroxy-5α-androstan-17-one comprises 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate.
73 . The method of claim 61 wherein the compound is 3β,16α-dihydroxy-5α-androstan-17-one.
74 . The method of claim 61 wherein the compound is 16β-bromo-3β-hydroxy-5α-androstan-17-one.
75 . The method of claim 61 wherein the compound is 3β,17β-dihydroxyandrost-5-ene.
76 . The method of claim 61 wherein the compound is 3β,7β,17β-trihydroxyandrost-5-ene.
77 . The method of claim 58 wherein the compound is 3α,17β-dihydroxy-16α-fluoroandrost-5-ene.
78 . A method to treat a subject having, or subject to developing, diabetes, hyperglycemia or a hyperlipidemia, comprising administering to the subject an effective amount of a compound having the structure
wherein R 1 is —OH, ═O, —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 group, a thioacyl group, a carbonate, a carbamate, a thioacetal, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an optionally substituted oligosaccharide, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
R 3 is —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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
R 4 is —OH, —OR PR , ═O, —SH, —SR PR , ═S, ═CH 2 , ═CH(CH 2 ) 0-15 CH 3 , —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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, or R 3 and both R 4 together comprise a structure of formula 2
R 5 and R 6 independently are —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 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
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, a nucleoside, a nucleotide, an oligonucleotide 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, a nucleoside, a nucleotide, an oligonucleotide 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 nucleoside, a nucleotide, an oligonucleotide or a polymer, or, one more of the ring carbons are substituted with ═0 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 is a protecting group;
R 13 independently are C1-C6 alkyl.
79 . The method of claim 78 wherein the compound is 3α,17β-dihydroxy- 16α-fluoroandrost-5-ene, 3α-hydroxy-16α-fluoroandrost-5-ene-17-one, 3α,17β-dihydroxy-16α-fluoroandrost-4-ene or 3α-hydroxy-16α-fluoroandrost-4-ene-17-one.
80 . The method of claim 78 wherein the level or activity of PPARα, LXRα or SF-1 is modulated in the subject.
81 . The method of claim 78 wherein the hyperlipidemia is hypercholesterolemia.
82 . A method to treat a subject having, or subject to developing, diabetes, hyperglycemia or a hyperlipidemia, comprising administering to the subject an effective amount of a compound having the structure
wherein R 2 is —OH, —OR PR , ═O, —SH, —SR PR , ═S, ═CH 2 , —N 3 , —NH 2 , —N(RPR) 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
R 3 is —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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
R 4 is —OH, —OR PR , ═O, —SH, —SR PR , ═S, ═CH 2 , ═CH(CH 2 ) 0-15 CH 3 , —N 3 , —NH 2 , —N(RPR) 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, or R 3 and both R 4 together comprise a structure of formula 2
R 5 and R 6 independently are —H, —OH, —OR PR , —SH, —SR PR , —N 3 , —NH 2 , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —CH 3 , —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 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, or,
R 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, a nucleoside, a nucleotide, an oligonucleotide 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 9 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, a nucleoside, a nucleotide, an oligonucleotide 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 nucleoside, a nucleotide, an oligonucleotide 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, provided that the compound is not 3β-hydroxyandrost-5-ene-17-one, 3β-hydroxyandrost-5-ene-1 7-one 3-sulfate or an ester or ether derivative of either compound;
R PR is a protecting group;
R 13 independently are C1-C6 alkyl.
83 . The method of claim 82 wherein the compound is 7α,17β-dihydroxy-16α-fluoroandrost-5-ene, 7α-hydroxy-16α-fluoroandrost-5-ene-17-one, 7β,17β-dihydroxy-16α-fluoroandrost-4-ene or 7β-hydroxy-16α-fluoroandrost-4-ene-17-one.
84 . The method of claim 82 wherein the level or activity of PPARα, LXRα or SF-1 is modulated in the subject.
85 . The method of claim 82 wherein the hyperlipidemia is hypercholesterolemia.
86 . A method to treat or prevent an infection in a subject in need thereof, wherein the method comprises administering to the subject an effective amount of a formulation comprising (1) one or more excipients and (2) a compound(s) selected from the group consisting of (i) 16α-bromo-3β-hydroxy-5α-androstan-17-one, (ii) 16β-bromo-3β-hydroxy-5α-androstan-17-one, (iii) 16α-bromo-3β-hydroxy-5α-androstan-17-one and 16β-bromo-3β-hydroxy-5α-androstan-17-one and (iv) 3β,16α-dihydroxy-5α-androstan-17-one, and wherein the infection is selected from the group consisting of a Plasmodium infection, a Trypanosoma infection, a togavirus infection, a flavivirus infection, a hepadnavirus infection, a papillomavirus infection, a Candida infection, a Mycoplasma infection, a Cryptosporidium infection or a Toxoplasma infection.
87 . The method of claim 86 wherein the pathogen infection is a togavirus infection, a flavivirus infection or a hepadnavirus infection.
88 . The method of claim 87 wherein the togavirus infection, flavivirus infection or hepadnavirus infection is a hepatitis C virus infection or a hepatitis B virus infection.
89 . The method of claim 29 wherein the pathogen infection is a Plasmodium infection.
90 . A liquid formulation that contains less than about 3% v/v water and comprises (1) 16α-bromo-3β-hydroxy-5α-androstan-17-one and/or 16β-bromo-3β-hydroxy-5α-androstan-17-one and (2) liquid excipients selected from the group consisting of (i) propylene glycol, a polyethylene glycol and ethanol, (ii) propylene glycol, a polyethylene glycol and benzyl alcohol, (iii) propylene glycol and a polyethylene glycol and (iv) propylene glycol, a polyethylene glycol and benzyl benzoate.
91 . The formulation of claim 90 wherein the formulation comprises less than about 0.3% v/v water.
92 . The formulation of claim 90 wherein the formulation contains about 0.5-100 mg/mL of 16α-bromo-3β-hydroxy-5α-androstan-17-one.
93 . The formulation of claim 92 wherein the formulation comprises less than about 0.3% v/v water.
94 . The formulation of claim 89 wherein the formulation further comprises a local anaesthetic.
95 . A product produced by the process of contacting a composition comprising 16α-bromo-3β-hydroxy-5α-androstan-17-one and/or 16β-bromo-3β-hydroxy-5α-androstan-17-one and two liquid excipients with a third liquid excipient wherein the product comprises less than about 3% v/v water.
96 . The product of claim 95 wherein the product comprises less than about 0.3% v/v water.
97 . The product of claim 95 wherein the two liquid excipients are selected from a polyethylene glycol, propylene glycol, benzyl benzoate and an alcohol selected from the group consisting of benzyl alcohol and ethanol.
98 . The product of claim 95 wherein the third liquid excipient is a polyethylene glycol, propylene glycol, benzyl benzoate or ethanol.
99 . A product produced by the process of contacting a composition comprising 16α-bromo-3β-hydroxy-5α-androstan-17-one or 16β-bromo-3β-hydroxy-5α-androstan-17-one and three liquid excipients with a fourth liquid excipient wherein the product comprises less than about 3% v/v water.
100 . The product of claim 99 wherein the product comprises less than about 0.3% v/v water.
101 . The product of claim 99 wherein the three liquid excipients are selected from a polyethylene glycol, propylene glycol, benzyl benzoate and an alcohol selected from the group consisting of benzyl alcohol and ethanol.
102 . The product of claim 101 wherein the fourth liquid excipient is a polyethylene glycol, propylene glycol, benzyl benzoate, benzyl alcohol or ethanol.
103 . The product of claim 95 wherein the product has been stored in a closed container at about 5-40° C. for about 30 minutes to about 2 years.
104 . The product of claim 99 wherein the product has been stored in a closed container at about 5-40° C. for about 30 minutes to about 2 years.
105 . A compound having the structure
wherein the dotted lines are optional double bonds;
R 1 is —H;
R 2 is —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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
R 3 is —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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
R 4 independently are —H, —OH, —OR PR , ═O, —SH, —SR PR , ═S, ═CH 2 , ═CH(CH 2 ) 0-15 CH 3 , —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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, provided that both R 4 are not —H, or R 3 and both R 4 together comprise a structure of formula 2
R 5 and R 6 independently are —H, —OH, —OR PR , —SH, —SR PR , —N 3 , —NH 2 , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CN, —CH 3 , —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 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer, or,
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, a nucleoside, a nucleotide, an oligonucleotide 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
R 9 is —CHR 10 —, —CHR 10 —CHR , —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 10 independently are —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, 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 nucleoside, a nucleotide, an oligonucleotide 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, provided that the compound is not 3β-hydroxyandrost-5-ene-17-one, 3β-hydroxyandrost-5-ene-1 7-one 3-sulfate or an ester or ether derivative of either compound;
R PR is a protecting group;
R 13 independently are C1-C6 alkyl.
106 . The compound of claim 105 having the structure
107 . The compound of claim 105 wherein the compound is 7β-hydroxy-16α-fluoroandrost-5-ene-17-one, 7α-hydroxy-16α-fluoroandrost-5-ene-17-one, 16α-fluoroandrost-5-ene-7,17-dione, 7β,17β-dihydroxy-16α-fluoroandrost-5-ene or 7α,17β-dihydroxy-16α-fluoroandrost-5-ene.
108 . A formulation comprising one or more excipients and a compound of claim 105 .
108 . A formulation comprising one or more excipients and a compound of claim 106 .
109 . A formulation comprising one or more excipients and a compound of claim 107 .
110 . The method of claim 34 wherein the condition is an allergy or inflammation condition.
111 . The method of claim 110 , wherein the allergy or inflammation condition is allergic bronchopulmonary aspergillosis , atopic asthma, allergic respiratory disease, allergic rhinitis, atopic dermatitis, lung fibrosis, subepithelial fibrosis in airway hyperresponsiveness, chronic sinusitis, perennial allergic rhinitis, Crohn's disease, ulcerative colitis, inflammatory bowel disease, chronic diarrhea or fibrosing alveolitis.
110 . The method of claim 34 , wherein the condition is an autoimmune disease.
111 . The method of claim 27 , wherein the autoimmune disease is systemic lupus erythematosus, myasthenia gravis , Grave's disease, diabetes, rheumatoid arthritis or osteoarthritis.
112 . A compound having the structure
wherein, the dotted lines are optional double bonds;
R 1 and R 2 independently are —OH, —OR PR , —SH, —SR PR , —O—Si—(R 13 ) 3 , an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide or an optionally substituted oligosaccharide;
R 3 is —OH, —OR PR , —SH, —SR PR , —O—Si—(R 13 ) 3 , —F, —Cl, —Br, —I, an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide or an optionally substituted oligosaccharide;
each R 4 independently is —OH, —OR PR , —SH, —SR PR , —O—Si—(R 13 ) 3 , an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide or an optionally substituted oligosaccharide, provided that both R 4 are not —H;
R 5 and R independently are —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 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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
R 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 —;
R 8 and R 9 independently are —CHR 10 —, —CHR 10 —CHR 10 —, —O—, —O—CHR 10 —, —S—, —S—CHR 10 —, —NR PR — or —NR PR —CHR 10 —, or R 8 or R 9 independently is absent, leaving a 5-membered ring;
R 10 independently are —H, —OH, ═O, —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, a nucleoside, a nucleotide, an oligonucleotide or a polymer;
R 13 independently are C 16 alkyl; and
R PR independently are a protecting group.
113 . A formulation comprising a compound of claim 105 and one or more excipients.
114 . The formulation of claim 113 wherein the formulation is for buccal or sublingual administration to a human.
115 . The formulation of claim 113 wherein the formulation is for parenteral or topical administration to a human.
116 . A formulation comprising a compound of claim 112 and one or more excipients.
117 . The formulation of claim 116 wherein the formulation is for buccal or sublingual administration to a human.
118 . The formulation of claim 116 wherein the formulation is for parenteral or topical administration to a human.
119 . The compound of claim 112 having the structure
wherein, R 4 is —OH, —OR PR , —SH, —SR PR , —O—Si—(R 13 ) 3 , an ester, a thioester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an ether, a thioether, a carbonate, a carbamate, an optionally substituted monosaccharide or an optionally substituted oligosaccharide.
120 . The compound of claim 119 wherein R 1 , R 2 , R 3 and R 4 are —OH.
121 . The compound of claim 119 wherein R 1 , R 2 and R 4 are —OH and R 3 is —F, —Cl, —Br or —I.
122 . A formulation comprising a compound of claim 119 and one or more excipients.
123 . The formulation of claim 122 wherein the formulation is for buccal or sublingual administration to a human.
124 . The formulation of claim 122 wherein the formulation is for parenteral or topical administration to a human.Join the waitlist — get patent alerts
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