5-Beta, 14-Beta-Androstane Derivatives Useful For The Treatment Of Proteinuria, Glomerulosclerosis And Renal Failure

1 . Compound of formula (I),

wherein:

the symbol represents a single or a double bond;

Y is oxygen or guanidinoimino when in position 3 is a double bond;

Y is hydroxy, OR 4 or SR 4 , when in position 3 is a single bond and can have an alpha or beta configuration;

R is an unsubstituted or substituted 3-furyl or 4-pyridazinyl group;

R 1 is hydrogen; methyl; ethyl or n-propyl substituted by OH or NR 5 R 6 ;

R 2 is hydrogen or together to R 3 is a bond of an oxirane ring;

R 3 is hydrogen or together to R 2 is a bond of an oxirane ring;

R 4 is hydrogen; methyl; C2-C6 alkyl or C3-C6 alkenyl or C2-C6 acyl, these alkyl, alkenyl and acyl groups being unsubstituted or substituted by a quaternary ammonium group or one or more OR 7 , NR 8 R 9 , formyl, amidino, guanidinoimino or by NR 8 R 9 and hydroxy;

R 5 , R 6 are independently hydrogen; methyl; C2-C6 alkyl unsubstituted or substituted by one NR 10 R 11 , or NR 10 R 11 and hydroxy, or R 5 and R 6 taken together with the nitrogen atom form an unsubstituted or substituted saturated or unsaturated penta- or hexa-monoheterocyclic ring, optionally containing another heteroatom chosen from oxygen or sulfur or nitrogen;

R 7 is hydrogen, methyl or C2-C4 alkyl, this alkyl being unsubstituted or substituted by one or more NR 10 R 11 or by NR 10 R 11 and hydroxy;

R 8 , R 9 are independently hydrogen; methyl; C2-C6 alkyl or C3-C6 alkenyl, these alkyl and alkenyl groups being unsubstituted or substituted by one or more NR 10 R 11 , or NR 10 R 11 and hydroxy, or R 8 and R 9 taken together with the nitrogen atom form an unsubstituted or substituted saturated or unsaturated penta- or hexa-monoheterocyclic ring, optionally containing another heteroatom chosen from oxygen or sulfur or nitrogen, or R 8 is hydrogen and R9 is amidino; or NR 8 R 9 represents propargylamino,

R 10 , R 11 are independently hydrogen, C1-C6 alkyl, or R 10 and R 11 , taken together with the nitrogen atom form a saturated or unsaturated penta- or hexa-monoheterocyclic ring; for use as antiproteuremic agent.

2 . Compound of formula (I) of claim 1 , for use as anti-glomerosclerotic agent.

3 . Compound of formula (I) of claim 1 , for use as anti renal failure agent.

4 . Compound of formula (I) of claim 1 , selected from the group consisting of:

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol;

3-β-(2-hydroxyethoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-aminoethoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(3-aminopropoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-methylaminoethoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-(1-pyrrolidinyl)ethoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-(3-(1-pyrrolidinyl)propoxy)ethoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(3-(1-pyrrolidinyl)propoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-(1-imidazolyl)ethoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-(2-imidazolin-2-yl)ethoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-(2-amidino)ethoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-(2-(1-pyrrolidinyl)ethoxy)ethoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-guanidinoethoxy)-17-β-(3-furyl)5-β-androstane-14-β, 17-α-diol;

3-β-(3-guanidinopropoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(3-amino-2-hydroxypropoxy)-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2,3-diaminopropoxy)-17-β-(3-furyl)5-β-androstane-14-β, 17-α-diol;

17-β-(3-furyl)-17-α-methoxy-5-β-androstane-3-β, 14-β-diol;

17-β-(3-furyl)-17-α-(2-(1-pyrrolidinyl)ethoxy)-5-β-androstane-3-β, 14-β-diol;

17-β-(3-furyl)-17-α-(3-aminopropoxy)-5-β-androstane-3-β, 14-β-diol;

3-β-(2-(1-pyrrolidinyl)ethoxy)-17-β-(3-furyl)-17-α-methoxy-5-β-androstan-14-β-ol;

3-β, 17-α-bis(2-(1-pyrrolidinyl)ethoxy)-17-β-(3-furyl)-5-β-androstan-14-β-ol;

3-β, 17-α-bis(3-aminopropoxy)-17-β-(3-furyl)-5-β-androstan-14-β-ol;

14-β, 17-α-dihydroxy-17-β-(3-furyl)-5-β-androstan-3-one,

3-guanidinoimino-17-β-(3-furyl)-5-β-androstane-14-β, 17-α-diol;

17-β-(4-pyridazinyl)-5-β-androstane-3-β, 14-β, 17-α-triol;

3-β-(2-hydroxyethoxy)-17-β-(4-pyridazinyl)5-β-androstane-14-β, 17-α-diol;

3-β-(3-aminopropoxy)-17-β-(4-pyridazinyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(2-(1-pyrrolidinyl)ethoxy)-17-β-(4-pyridazinyl)-5-β-androstane-14-β, 17-α-diol;

3-β-(3-(1-pyrrolidinyl)propoxy)-17-β-(4-pyridazinyl)-5-β-androstane-14-β, 17-α-diol;

17-β-(4-pyridazinyl)-17-α-(3-aminopropoxy)-5-β-androstane-3-β, 14-β-diol;

3-β-(2-(1-pyrrolidinyl)ethoxy)-17-β-(4-pyridazinyl)-17-α-methoxy-5-β-androstan-14-β-ol;

3-β-(2-(1-pyrrolidinyl)ethoxy)-17-β-(4-pyridazinyl)-17-α-(3-amino-propoxy)-5-β-androstan-14-β-ol;

14-β,17-α-dihydroxy-17-β-(4-pyridazinyl)-5-β-androstan-3-one;

3-guanidinoimino-17-β-(4-pyridazinyl)-5-β-androstane-14-β, 17-α-diol;

14-β, 15-β-epoxy-17-β-(3-furyl)-5-β-androstane-3-β, 17-α-diol;

3-β-(2-hydroxyethoxy)-14-β, 15-β-epoxy-17-β-(3-furyl)-5-β-androstan-17-α-ol;

3-β-(3-aminopropoxy)-14-β, 15-β-epoxy-17-β-(3-furyl)-5-β-androstan-17-α-ol;

3-β-(2-(1-pyrrolidinyl)ethoxy)-14-β, 15-β-epoxy-17-β-(3-furyl)-5-β-androstan-17-α-ol;

3-β-(3-(1-pyrrolidinyl)propoxy)-14-β, 15-β-epoxy-17-β-(3-furyl)-5-β-androstan-17-α-ol;

3-β-(2-(1-pyrrolidinyl)ethoxy)-17-β-(3-furyl)-17-α-methoxy-14-β, 15-β-epoxy-5-β-androstane;

17-α-hydroxy-17-β-(3-furyl)-14-β, 15-β-epoxy-5-β-androstan-3-one;

3-guanidinoimino-17-β-(3-furyl)-14-β, 15-β-epoxy-5-β-androstan-17-α-ol;

14-β, 15-β-epoxy-17-β-(4-pyridazinyl)-5-β-androstane-3-β, 17-α-diol;

and the 3 alpha derivatives of the above identified 3-β derivatives and also the corresponding 3 alpha and 3-β thioderivatives where Y═S.

5 . Use of a compound of formula (I) of claim 1 , for preparing a medicament for the prevention and/or treatment of proteinuria, glomerulosclerosis and renal failure.

6 . Use according to claim 5 , in which the preferred compound is 17-β-(3-Furyl)-5-β-androstane-3-β, 14-β, 17-α-triol.

7 . Use according to claim 5 , in which the compound is administered in a dose of from 0.05 mg to 20 mg per day.

8 . Use according to claim 7 , in which the compound is administered in a dose of from 0.5 mg to 15 mg.

9 . Use according to claim 8 , in which the compound is administered in a dose of from 5 mg to 10 mg.

10 . Use according to claims 7 - 9 in which the compound is administered in a single dose schedule.

11 . Use according to claims 7 - 9 , in which the compound is administered in a multiple dose schedule.

12 . Use according to claim 5 , in which the medicament is for oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, transdermal, transcutaneous, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal administration.