Pharmaceutical compounds

Abstract

The invention provides a compound for use in the treatment of T-Cell Acute Lymphoblastic Leukaemia (T-ALL), the compound having the formula (1):or being a pharmaceutically acceptable salt thereof; wherein:n is 0, 1 or 2;Ar1 is selected from an optionally substituted phenyl, pyridyl, thienyl and furanyl;Q1 is selected from C(═O), S(═O) and SO2;A is absent or is NR2;R1 is selected from:hydrogen;an optionally substituted C1-6 non-aromatic hydrocarbon group; andoptionally substituted 3- to 7-membered non-aromatic carbocyclic and heterocyclic rings containing one or two heteroatom ring members selected from O, N and S, and bridged bicyclic heterocyclic rings of seven to nine ring members of which one or two are nitrogen atoms, the carbocyclic and heterocyclic rings and bridged bicyclic heterocyclic rings;R2 is selected from hydrogen and C1-4 alkyl; orNR1R2 forms an optionally substituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic ring optionally containing a second heteroatom ring member selected from nitrogen and oxygen.

1 - 14 . (canceled) 
     
     
         15 . A method for the treatment or prophylaxis of a cancer characterised by abnormally elevated levels of any one or more of phosphorylated STAT1, phosphorylated STAT3 and phosphorylated STAT5, which method comprises administering to a patient, optionally in combination with radiotherapy or another chemotherapeutic agent, a therapeutically effective amount of a compound of formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof 
       
     
     
         16 . A method according to  claim 15  wherein the method comprises inhibiting TYK2 kinase in the patient. 
     
     
         17 . A method of alleviating or reducing the incidence of a cancer characterised by abnormally elevated levels of any one or more of phosphorylated STAT1, phosphorylated STAT3 and phosphorylated STAT5 and/or BCL2 in a subject in need thereof, which method comprises administering to the subject a therapeutically effective amount of compound of the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         18 . A method according to  claim 17  wherein the method comprises inhibiting TYK2 kinase in the subject. 
     
     
         19 . A method according to  claim 17  wherein the subject is a human subject. 
     
     
         20 . A method according to  claim 18  wherein the subject is a human subject. 
     
     
         21 . A method for the treatment or prophylaxis of a cancer characterised by abnormally elevated levels of BCL2, which method comprises administering to a patient, optionally in combination with radiotherapy or another chemotherapeutic agent, a therapeutically effective amount of a compound of the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof 
       
     
     
         22 . A method according to  claim 21  wherein the method comprises inhibiting TYK2 kinase in the patient. 
     
     
         23 . A method according to  claim 21  wherein the patient is a human patient. 
     
     
         24 . A method according to  claim 22  wherein the patient is a human patient. 
     
     
         25 . A method for the treatment, or alleviating or reducing the incidence of, a cancer in a subject wherein the cancer is characterised by constitutive phosphorylation of STAT3, which method comprises administering to the subject an effective therapeutic amount of a compound of the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         26 . A method according to  claim 25  wherein the method comprises inhibiting TYK2 kinase in the subject. 
     
     
         27 . A method according to  claim 25  wherein the subject is a human subject. 
     
     
         28 . A method according to  claim 26  wherein the subject is a human subject.