Pyrimidine derivatives

Abstract

The compounds of the present invention inhibit the HMG-CoA reductase, and subsequently suppress the biosynthesis of cholesterol. And they are useful in the treatment of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis.

What is claimed is:  
     
       1. A compound represented by the formula (I):                    
       wherein 
       R 1  is (1) lower alkyl which may have 1 to 3 substitutents independently selected from the group consisting of halogen, amino, and cyano, (2) C 6  to C 12  aromatic group which may have 1 to 3 substituents independently selected from the group consisting of lower alkyl, halogen, amino, and cyano, or (3) C 1  to C 6  lower alkyl substituted by C 6  to C 12  aromatic group which may have 1 to 3 substituents independently sel-ected from the group consisting of lower alkyl, halo-gen, amino, and cyano; R 2  and R 3  each is independently (1) hydrogen, (2) lower alkyl which may have 1 to 3 substituents independently selected from the group consisting of halogen, amino, and cyano, or (3) C 6  to C 12  aromatic group which may have 1 to 3 substituents independently selected from the group consisting of lower alkyl, halogen, amino, and cyano; R 4  is (1) hydro-gen, (2) lower alkyl, or a cation capable of forming a non-toxic pharmaceutically acceptable salt; X is sulfur, oxygen, or sulfonyl, or imino which may be substituted by formyl, acetyl, propionyl, butyryl, isobutyryl, vale-ryl, isovaleryl, amino substituted by sulfonyl or alkyl-sulfonyl, and sulfonyl substituted by alkyl, amino or alkylamino, the dotted line represents the presence or absence of a double bond, or the corresponding ring-closed lactone.  
     
     
       2. The compound claimed in claim  1 , wherein X is imino which may be substituted by formyl, acetyl, pro-pionyl, butyryl, isobutyryl, valeryl, isovaleryl, amino substituted by sulfonyl or alkylsulfonyl, or sulfonyl substituted by alkyl, amino or alkylamino. 
     
     
       3. The compound claimed in claim  2 , wherein X is imino which may be substituted by formyl, acetyl, pro-pionyl, butyryl, isobutyryl, valeryl, isovaleryl, alkylsul-fonylamino, or alkylsulfonyl. 
     
     
       4. The compound claimed in claim  1  having the (3R, 5S)-dihydroxy configuration. 
     
     
       5. A pharmaceutical composition comprising an ef-fective amount of the compound claimed in claim  1  as an active ingredient, in combination with a pharmaceu-tical excipient. 
     
     
       6. The compound  7 -(   4   -(   4   - fluorophenyl )-   6   - isopropyl -   2   -( N - methyl - N - methylsulfonylamino ) pyrimidin -   5   - yl )-(   3 R, 5 S )- dihydroxy -( E )-   6   - heptenoic acid in the form of a non - toxic pharmaceutically acceptable salt thereof.   
     
     
       7. The compound of claim  6  in the form of a sodium salt. 
     
     
       8. The compound of claim  6  in the form of a calcium salt.