Meiosis regulating compounds

Abstract

Certain novel sterol derivatives can be used for regulating the meiosis in oocytes and in male germ cells.

1. A method of regulating meiosis comprising administering to a subject in need thereof an effective amount of the compound of formula Ic: 
                 
 wherein R 1  is hydrogen, halogen, methyl, hydroxyl or oxo;  
 R 2  is selected from the group consisting of hydrogen, hydroxyl, C 1 -C 3  alkyl, vinyl, C 1 -C 3  alkoxy and halogen;  
 R 3  is selected from the group consisting of hydrogen and optionally substituted alkoxy, acyloxy, sulphonyloxy, and phosphonyloxy;  
 R′ 3  designates hydrogen or hydroxyl;  
 R 4  and R′ 4 , which are different or identical with the proviso that they are not both hydroxyl, are selected from the group comprising hydrogen, halogen, hydroxyl and C 1 -C 6  alkyl which may be substituted by halogen, hydroxyl or cyano;  
 R 5  is hydrogen, halogen, hydroxyl, lower alkyl, cyano, hydroxymethyl, a carbaldehyde, an oxime derived from a carbaldehyde, a carboxylic acid, a primary or secondary amine derived from a carboxylic acid or an ester with a C 1 -C 6 -alcohol group;  
 R 6  is hydrogen, hydroxyl, halogen or oxo;  
 R 7  is selected from the group consisting of hydrogen, hydroxyl, lower alkoxy, acyloxy, halogen and lower alkyl;  
 R′ 7  is hydrogen, or, if R 7  is lower alkyl, R′ 7  is hydrogen or hydroxyl;  
 R 8  designates together with R 9  an additional bond between the carbon atoms at which R 8  and R 9  are placed;  
 R 11  is selected from the group consisting of hydrogen, hydroxyl, lower alkoxy, acyloxy, halogen and lower alkyl;  
 R′ 11  is hydrogen or, if R 11  is lower alkyl, R′ 11  is hydrogen or hydroxyl;  
 R 12  is selected from the group consisting of hydrogen, halogen, C 1 -C 4  alkyl, methylene, hydroxyl, lower alkoxy, acyloxy, oxo and a group of the general formula ═NOR 33  wherein R 33  is hydrogen or C 1 -C 3  alkyl;  
 R 14  designates together with R 15  an additional bond between the carbon atoms at which R 14  and R 15  are placed;  
 R 16  is selected from the group consisting of hydrogen, halogen, C 1 -C 3  alkyl, methylene, hydroxyl, lower alkoxy, oxo and a group of the general formula ═NOR 34  wherein R 34  is hydrogen or lower alkyl;  
 R 17  is hydrogen or hydroxyl;  
 R 20  is selected from the group consisting of hydrogen, lower alkyl and hydroxymethyl or R 20  and R′ 20  together designate methylene or oxo;  
 R′ 20  is hydrogen, halogen, lower alkyl or hydroxyl;  
 R′ 22  is hydrogen, hydroxyl or oxo; and 
 R 22  is cyclohexyl or cyclohexylalkyl, each optionally substituted by one or more of the following groups which substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxy, a group of the general formula —COOR 39 , oxo, N-alkylamino or N,N-dialkylamino wherein the N-alkylamino or N,N-dialkylamino substituent optionally is substituted by carboxy, lower alkoxy or lower alkylthio; and wherein R 39  is lower alkyl or aralkyl.  
 
     
     
       2. The method of  claim 1 , wherein the compound is ( 20 R)- 4 , 4 - 20 ,trimethyl- 21 -(cyclohexyl)- 5 α-pregna- 8 ,-dien- 3 β-ol  ( 20 R)- 4 , 4 , 20 -trimethyl- 21 -(cyclohexyl)- 5 α-pregna- 8 ,-dien- 3 β-ol. 
     
     
       3. The method of  claim 1 , wherein meiosis is regulated in a mammalian germ cell. 
     
     
       4. The method of  claim 3 , wherein the compound is administered to a germ cell located in a mammalian host. 
     
     
       5. The method of  claim 4 , wherein the germ cell an oocyte. 
     
     
       6. The method of  claim 3 , wherein the compound is administered to an oocyte ex vivo or in vitro. 
     
     
       7. The method of  claim 4 , wherein the germ cell is a male germ cell. 
     
     
       8. The method of  claim 7 , wherein the compound is administered to testicular tissue in vivo, ex vivo or in vitro.