Pharmaceutical compounds

Abstract

Fused pyrimidines of formula (I): wherein R 1 -R 3 , A and n have any of the values described in the specification; and pharmaceutically acceptable salts thereof; have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

1 . A pharmaceutical composition comprised of a fused pyrimidine compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         A represents a thiophene or furan ring; 
         n is 1 or 2; 
         R 1  is a group of formula: 
       
       
         
           
           
               
               
           
         
         wherein 
         m is 0 or 1; 
         R 30  is H or C 1 -C 6  alkyl; 
         R 4  and R 5  form, together with the N atom to which they are attached, a 5- or 6-membered saturated N-containing heterocyclic group which includes 0 or 1 additional heteroatoms selected from N, S and O, which may be fused to a benzene ring and which is unsubstituted or substituted; or one of R 4  and R 5  is alkyl and the other is a 5- or 6-membered saturated N-containing heterocyclic group as defined above or an alkyl group which is substituted by a 5- or 6-membered saturated N-containing heterocyclic group as defined above; 
         R 2  is selected from: 
       
       
         
           
           
               
               
           
         
         
           wherein R 6  and R 7  form, together with the nitrogen atom to which they are attached, a morpholine, thiomorpholine, piperidine, piperazine, oxazepane or thiazepane group which is unsubstituted or substituted; and 
         
       
       
         
           
           
               
               
           
         
         
           wherein Y is a C 2 -C 4  alkylene chain which contains, between constituent carbon atoms of the chain and/or at one or both ends of the chain, 1 or 2 heteroatoms selected from O, N and S, and which is unsubstituted or substituted; and 
         
         R 3  is an indazole group which is unsubstituted or substituted; 
         or a pharmaceutically acceptable salt thereof, and a carrier, diluent or excipient selected from calcium carbonate, sodium carbonate, calcium phosphate, sodium phosphate, cellulose, lactose, sodium carboxymethylcellulose, talc, calcium stearate, glyceryl monostearate, methylcellulose, hydroxypropylmethyl-cellulose, polyvinylpyrrolidone, gum tragacanth, gum acacia, glyceryl distearate, polysorbate, lauryl sulphate and magnesium stearate. 
       
     
     
         2 . The pharmaceutical composition of  claim 1  formulated in a capsule. 
     
     
         3 . The pharmaceutical composition of  claim 1  formulated in a tablet. 
     
     
         4 . The pharmaceutical composition of  claim 1  formulated in the form of oil-in-water emulsion. 
     
     
         5 . The pharmaceutical composition of  claim 4  comprising an amount of 10 mg to 1000 mg of the thienopyrimidine of formula (I). 
     
     
         6 . The pharmaceutical composition of  claim 5  comprising an amount of 100 mg to 300 mg of the thienopyrimidine of formula (I). 
     
     
         7 . The pharmaceutical composition formulated of  claim 1  comprising a carrier, diluent or excipient selected from lactose, sodium carboxymethylcellulose, and magnesium stearate. 
     
     
         8 . The pharmaceutical composition of  claim 3  comprising an amount of 10 mg to 1000 mg of the thienopyrimidine of formula (I). 
     
     
         9 . The pharmaceutical composition of  claim 8  comprising an amount of 100 mg to 300 mg of the thienopyrimidine of formula (I).