Quinazoline derivatives

Abstract

Quinazoline derivatives of the following formula: wherein R 1 , R 2 , R 3 , R 4 , R 5 , X, Y, and Z are defined herein. It also discloses a method of treating cancer with one of these compounds.

1 . A compound of the following formula: 
       
         
           
           
               
               
           
         
       
       in which
 each of R 1 , R 2 , and R 5 , independently, is H, halo, nitro, amino, cyano, hydroxy, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, alkoxy, alkylthio, alkylcarbonyl, carboxy, alkoxycarbonyl, carbonylamino, sulfonylamino, aminocarbonyl, or aminosulfonyl; 
 one of R 3  and R 4  is 
 
       
         
           
           
               
               
           
         
         in which n is 1, 2, 3, 4, or 5; each of R a , R b , and R c , independently, is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, or R b  and R c , together with the nitrogen atom to which they are attached, form a 3-12 membered saturated, unsaturated, or aromatic ring containing 1-3 heteroatoms selected from N, O and S; and each of R d  and R e , independently, is H, alkyl, alkenyl, or alkynyl; or R d  and R e , together with the nitrogen to which they are attached, form a 3-12 membered saturated, unsaturated, or aromatic ring containing 1-3 heteroatoms selected from N, O, and S; and the other of R 3  and R 4  is H, halo, nitro, amino, cyano, hydroxy, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, alkoxy, alkylthio, alkylcarbonyl, carboxy, alkoxycarbonyl, carbonylamino, sulfonylamino, aminocarbonyl, or aminosulfonyl; 
         X is NR f , wherein R f  is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, or aminosulfonyl; 
         Y is phenyl optionally substituted with halo, nitro, cyano, alkyl, alkenyl, or alkynyl, or optionally fused with another 3-8 membered ring; and 
         Z is N. 
       
     
     
         2 . The compound of  claim 1 , wherein one of R 3  and R 4  is 
       
         
           
           
               
               
           
         
         in which n is 1 and each of R a , R b , and R c , independently, is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl. 
       
     
     
         3 . The compound of  claim 1 , wherein one of R 3  and R 4  is 
       
         
           
           
               
               
           
         
         in which n is 1 or 2; R a  is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and R b  and R c , together with the nitrogen atom to which they are attached, form a 3-12 membered saturated, unsaturated, or aromatic ring containing 1-3 heteroatoms selected from N, O and S. 
       
     
     
         4 . The compound of  claim 3 , wherein R b  and R c , together with the nitrogen atom to which they are attached, form a bicyclic ring of the following formula: 
       
         
           
           
               
               
           
         
         wherein each of m 1 , m 2 , m 3 , and m 4 , independently, is 0, 1, 2, or 3; A is N or CR; B is NR or CRR′, each R and R′, independently, being H, alkyl, or halo; and each of R i , R ii , R iii , R iv , R v , R vi , R vii , and R viii , independently, is H, alkyl, or halo. 
       
     
     
         5 - 8 . (canceled) 
     
     
         9 . The compound of  claim 1 , wherein Y is 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 1 , wherein X is NH or N—CH 3 . 
     
     
         11 . The compound of  claim 10 , wherein Y is 
       
         
           
           
               
               
           
         
       
     
     
         12 - 14 . (canceled) 
     
     
         15 . The compound of  claim 1 , wherein one of R 3  and R 4  is 
       
         
           
           
               
               
           
         
       
       in which n is 1 and each of R a , R b , and R c , independently, is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl. 
     
     
         16 . The compound of  claim 11 , wherein one of R 3  and R 4  is 
       
         
           
           
               
               
           
         
       
       in which n is 1 or 2; R a  is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and R b  and R c , together with the nitrogen atom to which they are attached, form a 3-12 membered saturated, unsaturated, or aromatic ring containing 1-3 heteroatoms selected from N, O and S. 
     
     
         17 . The compound of  claim 16 , wherein R b  and R c , together with the nitrogen atom to which they are attached, form a bicyclic ring of the following formula: 
       
         
           
           
               
               
           
         
         wherein each of m 1 , m 2 , m 3 , and m 4 , independently, is 0, 1, 2, or 3; A is N or CR; B is NR or CRR′, each R and R′, independently, being H, alkyl, or halo; and each of R i , R ii , R iii , R iv , R v , R vi , R vii , and R viii , independently, is H, alkyl, or halo. 
       
     
     
         18 - 20 . (canceled) 
     
     
         21 . The compound of  claim 1 , wherein the compound is Compounds 91, 93-101, 103-104, and 106-125. 
     
     
         22 . A pharmaceutical composition, comprising a compound of  claim 1  and a pharmaceutically acceptable carrier thereof. 
     
     
         23 - 24 . (canceled)