Spirofuranone compounds, derivatives thereof and processes for their preparation

Abstract

The present invention provides compounds comprising fused tricyclic backbone structure and processes for their preparation. The invention further provides compounds and compositions useful in the treatment of pain and any type of disorder or symptom associated therewith.

1 . A compound of the general formula (I), including any stereoisomer thereof: 
       
         
           
           
               
               
           
         
         wherein 
         Ring A is optionally a saturated or unsaturated ring having optionally at least one heteroatom; 
         and is optionally substituted by at least one group selected from straight or branched C 1 -C 10  alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl, CN, —OR 4 , —NR 5 R 8 , —C(═O)R 7 , halogen; 
         R 4 , R 5  and R 6  are each independently selected from H, halogen, straight or branched C 1 -C 10 alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl; 
         R 7  is selected from H, straight or branched C 1 -C 10  alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl, halogen, OH, O(C 1 -C 10 )alkyl, NH 2 , amine; 
         n is an integer selected from 1-10; 
         —C (n) — is selected from a straight or branched alkylene, straight or branched alkenylene, straight or branched alkynylene; optionally interrupted by at least one heteroatom; 
         m is an integer selected from 1-10; 
         —C (m) — is selected from a straight or branched alkylene, straight or branched alkenylene, straight or branched alkynylene; optionally interrupted by at least one heteroatom; 
         R 1  is selected from —C(═O)R 8 , —C(═S)R 9 , —C(═P)R 10 , —C(═CR 11 R 12 )R 13 , straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl; 
         each of R 8 , R 9 , R 10 , R 11 , R 12  and R 13  are independently is selected from a group consisting of OH, —OR 14 , —NH 2 , —NHR 15 , —NR 16 R 17 ; 
         each of R 14 , R 15 , R 16  and R 17  are independently selected from straight or branched C 1 -C 10  alkyl; 
         R 2  is selected from S, CR 18 R 19 ; 
         each of R 18  and R 19  is independently selected from H, straight or branched C 1 -C 10  alkyl, halogen, CF 3 SO 3 , OH, C 1 -C 10  alkoxy, 
         l is an integer selected from 1-10; 
         —C (l) — is selected from a straight or branched alkylene, straight or branched alkenylene, straight or branched alkynylene; optionally interrupted by at least one heteroatom; 
         R 3  is selected from C(═O)R 20 , OR 21 , C(═O)OR 22 , CF 3 SO 3 , straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl; 
         each of alkenyl or alkylnyl groups are optionally substituted by at least one group selected from C(═O)R 23 , OR 24 , halogen, CF 3 SO 3 ; 
         each of R 20 , R 21 , R 22 , R 23  and R 24  is independently selected from H, OH, halogen, straight or branched C 1 -C 10  alkyl, straight or branched C 1 -C 10  alkoxy, NH 2 , amine. 
       
     
     
         2 . A compound according to  claim 1 , of the general formula (I), including any stereoisomer thereof: 
       
         
           
           
               
               
           
         
         provided that when R 2  is O than R 3  is selected from C(═O)R 20 , OR 21 , C(═O)OR 22 , CF 3 SO 3 , straight or branched C 2 -C 10  alkenyl, straight or branched C 1 -C 10  alkynyl; 
         each of alkenyl or alkylnyl groups are optionally substituted by at least one group selected from C(═O)R 23 , OR 24 , halogen, CF 3 SO 3 ; 
         each of R 20 , R 21 , R 22 , R 23  and R 24  is independently selected from H, OH, halogen, straight or branched C 1 -C 10  alkyl, straight or branched C 1 -C 10  alkoxy, NH 2 , amine. 
       
     
     
         3 . A compound according to  claim 1 , wherein Ring A is a saturated or unsaturated 5, 6, 7, or 8 member ring. 
     
     
         4 . A compound according to  claim 1 , wherein Ring A is a 5-7 member ring having at least one heteroatom. 
     
     
         5 . A compound according to  claim 1 , wherein —C (m) — is a C 1 -C 10  straight or branched alkylene. 
     
     
         6 . A compound according to  claim 1 , wherein R 2  is CH 2 . 
     
     
         7 . A compound according to  claim 1 , selected from
 a compound having the general formula (II)   
       
         
           
           
               
               
           
         
       
       including any stereoisomer thereof,
 a compound having the general formula (III) 
 
       
         
           
           
               
               
           
         
       
       including any stereoisomer thereof;
 a compound having the general formula (IV) 
 
       
         
           
           
               
               
           
         
       
       including any stereoisomer thereof;
 a compound having the general formula (V) 
 
       
         
           
           
               
               
           
         
       
       including any stereoisomer thereof;
 a compound having the general formula (VI) 
 
       
         
           
           
               
               
           
         
       
       including any stereoisomer thereof;
 a compound having the general formula (VII) 
 
       
         
           
           
               
               
           
         
       
       including any stereoisomer thereof;
 a compound having the general formula (VIII) 
 
       
         
           
           
               
               
           
         
       
       including any stereoisomer thereof;
 a compound having the general formula (IX) 
 
       
         
           
           
               
               
           
         
       
       including any stereoisomer thereof;
 a compound having the general formula (X) 
 
       
         
           
           
               
               
           
         
       
       including any stereoisomer thereof. 
     
     
         8 . A process for the preparation of compound of general formula (XIII) comprising a cyclization step of: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3 , n, m, l, are as defined above: Ring A, Ring B and Ring C are optionally a saturated or unsaturated ring having optionally at least one heteroatom; and each is optionally substituted by at least one group selected from branched C 1 -C 10  alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl, CN, —OR 4 , —NR 5 R 8 , —C(═O)R 7 , halogen;
 R 4 , R 8  and R 6  are each independently selected from H, halogen, straight or branched C 1 -C 10  alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 30  alkynyl; 
 R 7  is selected from H, straight or branched C 1 -C 10  alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl, halogen, OH, O(C 1 -C 30 )alkyl, NH 2 , amine. 
 
     
     
         9 . A process according to  claim 8 , wherein said cyclization step comprises the steps of:
 Step 4:   
       
         
           
           
               
               
           
         
         Step 5 
       
       
         
           
           
               
               
           
         
       
       including any stereoisomers thereof and wherein R 3 , R 29  and n, m, p and l are as defined above. 
     
     
         10 . A process according to  claim 8  wherein compound of formula (XIII) is: 
       
         
           
           
               
               
           
         
       
       including any stereoisomers thereof and wherein n, m, and l are as defined above. 
     
     
         11 . A composition comprising a compound of general formula (XIV): 
       
         
           
           
               
               
           
         
         wherein 
         Ring A is optionally a saturated or unsaturated ring having at least one heteroatom; and is optionally substituted by at least one group selected from straight or branched C 1 -C 10  alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl, CN, —OR 4 , —NR 5 R 6 , —C(═O)R 7 , halogen; 
         R 4 , R 5  and R 6  are each independently selected from H, halogen, straight or branched C 1 -C 10  alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl; 
         R 7  is selected from H, straight or branched C 1 -C 10  alkyl, straight or branched C 1 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl, halogen, OH, O(C 1 -C 10 )alkyl, NH 2 , amine; 
         n is an integer selected from 1-10; 
         —C (n) — is selected from a straight or branched alkylene, straight or branched alkenylene, straight or branched alkynylene; interrupted by at least one heteroatom; 
         m is an integer selected from 1-10; 
         —C (m) — is selected from a straight or branched alkylene, straight or branched alkenylene, straight or branched alkynylene; interrupted by at least one heteroatom; 
         l is an integer selected from 1-10; 
         —C (l) — is selected from a straight or branched alkylene, straight or branched alkenylene, straight or branched alkynylene; interrupted by at least one heteroatom; 
         R 3  and R 3 ′ are each independently selected from C(═O)R 20 , OR 21 , C(═O)OR 22 , CF 3 SO 3 , straight or branched C 2 -C 10  alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl; 
         each of alkyl, alkenyl or alkylnyl groups are optionally substituted by at least one group selected from C(═O)R 23 , OR 24 , halogen, CF 3 SO 3 ; 
         each of R 20 , R 21 , R 22 , R 23  and R 24  is independently selected from H, OH, halogen, straight or branched C 1 -C 10  alkyl, straight or branched C 1 -C 10  alkoxy, NH 2 , amine. 
       
     
     
         12 . A composition according to  claim 11 , wherein m=1, —C (m) — being a C 1 -alkylene interrupted by at least one heteroatom. 
     
     
         13 . A composition according to  claim 11 , wherein n=L, —C (n) — being C-alkylene, interrupted by at least one heteroatom. 
     
     
         14 . A composition according to  claim 11 , wherein n=2, —C (n) — being C 2 -alkylene, interrupted by at least one heteroatom. 
     
     
         15 . A composition according to  claim 11 , wherein n=3, —C (n) — being C 3 -alkylene, interrupted by at least one heteroatom. 
     
     
         16 . A composition according to  claim 11 , wherein I=1, —C (l) — is a C 1 -alkylene, interrupted by at least one heteroatom. 
     
     
         17 . A composition according to  claim 11 , wherein I=2, —C (l) — is a C 2 -alkenylene, interrupted by at least one heteroatom. 
     
     
         18 . A composition according to  claim 11 , wherein R 3  and R 3 ′ are each independently selected from OR 21 , straight or branched C 1 -C 10  alkyl, straight or branched C 2 -C 10  alkenyl, straight or branched C 2 -C 10  alkynyl; each of alkenyl or alkylnyl groups are optionally substituted by at least one group selected from C(═O)R 23 , OR 24 , halogen, CF 3 SO 3 ; each of R 20 , R 21 , R 22 , R 23  and R 24  is independently selected from H, OH, halogen, straight or branched C 1 -C 10  alkyl, straight or branched C 1 -C 10  alkoxy, NH 2 , amine. 
     
     
         19 . A method of treating pain and pain related disorders and symptoms in a subject in need thereof, said method comprising administering to a patient a composition according to  claim 11 .