17-Substituted Steroid Compounds

Abstract

The invention relates to the use of compounds to ameliorate or treat an condition such as a cystic fibrosis, neutropenia or other exemplified conditions. Exemplary compounds that can be used include 3β-hydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3α-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-16β-fluoro-17β-aminoandrost-5-ene, 1α,3β-dihydroxy-4α-fluoroandrost-5-ene-17-one, 1α,3β,17β-trihydroxy-4α-fluoroandrost-5-ene, 1β,3β-dihydroxy-6α-bromoandrost-5-ene, 1α-fluoro-3β,12α-dihydroxyandrost-5-ene-17-one, 1α-fluoro-3β,4α-dihydroxyandrost-5-ene and 4α-fluoro-3β,6α,17β-trihydroxyandrostane.

What is claimed is: 
     
         1 . A compound having the structure 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is —OH, ═O or an ester; 
         R 2  and R 3  are —H; 
         R 4  is an N-linked heterocycle selected from the group consisting of N-pyrrolidine, N-pyridine, N-pyrazolone, N-piperidine, N-morpholine, N-indoline, N-indole, N-benzimidazole, N-benzotriazole, N-benzisoxazole and N-benzoxazole. 
       
     
     
         2 . The compound of  claim 1  having the structure 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound of  claim 2  having the structure 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 3  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound of  claim 3  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 3  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 1  having the structure 
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 7  having the structure 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 8  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 8  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 8  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound of  claim 1  having the structure 
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound of  claim 12  having the structure 
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 13  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
     
     
         15 . The compound of  claim 13  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 13  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of  claim 3  wherein R 1  is ═O and R 4  is N-indoline, N-benzimidazole, N-benzotriazole, N-benzisoxazole or N-benzoxazole. 
     
     
         18 . The compound of  claim 8  wherein R 1  is —OH and R 4  is N-indoline, N-benzimidazole, N-benzotriazole, N-benzisoxazole or N-benzoxazole. 
     
     
         19 . The compound of  claim 11  wherein R 1  is —OH and R 4  is N-indoline, N-benzimidazole, N-benzotriazole, N-benzisoxazole or N-benzoxazole. 
     
     
         20 . A pharmaceutical formulation comprising one or more excipients and a compound having the structure 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is —OH, ═O or an ester; 
         R 2  and R 3  are —H; 
         R 4  is an N-linked heterocycle selected from the group consisting of N-pyrrolidine, N-pyridine, N-pyrazolone, N-piperidine, N-morpholine, N-indoline, N-indole, N-benzimidazole, N-benzotriazole, N-benzisoxazole and N-benzoxazole. 
       
     
     
         21 . The pharmaceutical formulation comprising of  claim 20  wherein
 (1) the compound has the structure 
 
       
         
           
           
               
               
           
         
       
       and R 4  is N-pyrrolidine, N-pyridine, N-indoline, N-benzimidazole, N-benzotriazole, N-benzisoxazole or N-benzoxazole; or
 (2) the compound has the structure 
 
       
         
           
           
               
               
           
         
       
       and R 1  is —OH and R 4  is N-pyrrolidine, N-pyridine, N-indoline, N-benzimidazole, N-benzotriazole, N-benzisoxazole or N-benzoxazole.