Omega-Carboxyaryl Substituted Diphenyl Ureas As Raf Kinease Inhibitors

Abstract

This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.

1 .- 67 . (canceled)  
     
     
         68 . A compound of Formula I:  
         A-D-B  (I)  
       or a pharmaceutically acceptable salt thereof wherein 
 D is —NH—C(O)—NH—,  
 A is a substituted moiety of up to 40 carbon atoms of the formula: -L-(M-L 1 ) q , where L is a 6 membered aryl moiety which is unsubstituted phenyl bound directly to D, L 1  comprises a substituted cyclic moiety having at least 5 members which is phenyl pyridyl, M is —O— and  
 B is a substituted or unsubstituted, up to tricyclic aryl or heteroaryl moiety of up to 30 carbon atoms with at least one 6-member cyclic structure bound directly to D which is pyridinyl  
 wherein L 1  is substituted by —C(O)R x    
 R x  is NR a R b  where R a  and R b  are  
 a) independently hydrogen, 
 a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O, which is of C 1 -C 10  alkyl, C 1 -C 10  alkoxy, C 3-10  cycloalkyl, C 2-10  alkenyl, C 1-10  alkenoyl, C 6-12  aryl, C 3-12  hetaryl having 1-3 heteroatoms selected from O, N and S, C 3-12  cycloalkyl having 0-3 heteroatoms selected from N, S and O, C 7-24  aralkyl or C 7 -C 24  alkaryl, and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O, which are C 1-10  alkyl, C 3-12  cycloalkyl having 0-3 heteroatoms selected from O, S and N, C 3-12  hetaryl having 1-3 heteroatoms selected from N, S and O, C 1-10  alkoxy, C 6-12  aryl, C 1-6  halo substituted alkyl up to per halo alkyl, C 6 -C 12  halo substituted aryl up to per halo aryl, C 3 -C 12  halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C 3 -C 12  hetaryl up to per halo hetaryl, halo substituted C 7 -C 24  aralkyl up to per halo aralkyl, halo substituted C 7 -C 24  alkaryl up to per halo alkaryl, or —C(O)R g  or  
 —OSi(R f ) 3  where R f  is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O, which are C 1-10  alkyl, C 3-12  cycloalkyl having 0-3 heteroatoms selected from O, S and N, C 3-12  hetaryl having 1-3 heteroatoms selected from N, S and O, C 1-10  alkoxy, C 6-12  aryl, C 7 -C 24  alkaryl, C 7 -C 24  aralkyl, C 1-6  halo substituted alkyl up to per halo alkyl, C 6 -C 12  halo substituted aryl up to per halo aryl, C 3 -C 12  halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C 3 -C 12  hetaryl up to per halo hetaryl, halo substituted C 7 -C 24  aralkyl up to per halo aralkyl, halo substituted C 7 -C 24  alkaryl up to per halo alkaryl, or —C(O)R g , or  
 
 b) R a  and R b  together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O substituted by halogen, hydroxy or carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O, which are C 1-10  alkyl, C 3-12  cycloalkyl having 0-3 heteroatoms selected from O, S and N, C 3-12  hetaryl having 1-3 heteroatoms selected from N, S and O, C 1-10  alkoxy, C 6-12  aryl, C 7 -C 24  alkaryl, C 7 -C 24  aralkyl, halo substituted C 1-6  alkyl up to per halo alkyl, halo substituted C 6 -C 12  aryl up to per halo aryl, halo substituted C 3 -C 12  cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C 3 -C 12  hetaryl up to per halo hetaryl, halo substituted C 7 -C 24  aralkyl up to per halo aralkyl, halo substituted C 7 -C 24  alkaryl up to per halo alkaryl, or —C(O)R g , or  
 c) one of R a  or R b  is —C(O)—, a C 1 -C 5  divalent alkylene group or a substituted C 1 -C 5  divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C 1 -C 5  divalent alkylene group are selected from the group consisting of halogen, hydroxy, and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O, which are C 1-10  alkyl, C 3-12  cycloalkyl having 0-3 heteroatoms selected from O, S and N, C 3-12  hetaryl having 1-3 heteroatoms selected from N, S and O, C 1-10  alkoxy, C 6-12  aryl, C 7 -C 24  alkaryl, C 7 -C 24  aralkyl, C 1-6  halo substituted alkyl up to per halo alkyl, C 6 -C 12  halo substituted aryl up to per halo aryl, C 3 -C 12  halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C 3 -C 12  hetaryl up to per halo hetaryl, halo substituted C 7 -C 24  aralkyl up to per halo aralkyl, halo substituted C 7 -C 24  alkaryl up to per halo alkaryl, or —C(O)R g , and are optionally substituted by halogen;  
 where B is substituted, L is substituted or L 1  is additionally substituted, the substituents are selected from the group consisting of halogen, up to per-halo, and Wn, where n is 0-3;  
 wherein each W is independently selected from the group consisting of —CN, —CO 2 R 7 , —C(O)NR 7 R 7 , —C(O)—R 7 , —NO 2 , —OR 7 , —SR 7 , —NR 7 R 7 , —NR 7 C(O)OR 7 , —NR 7 C(O)R 7 , -Q-Ar, and carbon based moieties of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O, which are C 1 -C 10  alkyl, C 1 -C 10  alkoxy, C 2 -C 10  alkenyl, C 1 -C 10  alkenoyl, C 3 -C 10  cycloalkyl having 0-3 heteroatoms selected from O, S and N, C 6 -C 14  aryl, C 7 -C 24  alkaryl, C 7 -C 24  aralkyl, or C 3 -C 12  heteroaryl having 1-3 heteroatoms selected from O, N and S, and optionally substituted by one or more substituents independently selected from the group consisting of —CN, —CO 2 R 7 , —C(O)R 7 , —C(O)NR 7 R 7 , —OR 7 , —SR 7 , —NR 7 R 7 , —NO 2 , —NR 7 C(O)R 7 , —NR 7 C(O)OR 7  and halogen up to per-halo; with each R 7  independently selected from H or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O, which are C 1 -C 10  alkyl, C 1 -C 10  alkoxy, C 2 -C 10  alkenyl, C 1 -C 10  alkenoyl, C 3 -C 10  cycloalkyl having 0-3 heteroatoms selected from O, S and N, C 6 -C 14  aryl, C 3 -C 13  hetaryl having 1-3 heteroatoms selected from O, N and S, C 7 -C 14  alkaryl, C 7 -C 24  aralkyl, C 4 -C 23  alkheteroaryl having 1-3 heteroatoms selected from O, N and S, and optionally substituted by halogen,  
 wherein Q is —O—, —S—, —N(R 7 )—, —(CH 2 ) m —, —C(O)—, —CH(OH)—, —(CH 2 ) m O—, —(CH 2 ) m S—, —(CH 2 ) m N(R 7 )—, —O(CH 2 ) m —CHX a —, —CX a   2 —, —S—(CH 2 ) m — and —N(R 7 )(CH 2 ) m —, where m=1-3, and X a  is halogen;  
 Ar is a 5- or 6-member aromatic structure containing 0-2 members selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by halogen, up to per-halo, and optionally substituted by Z n1 , wherein n1 is 0 to 3 and each Z is independently selected from the group consisting of —CN, —CO 2 R 7 , —C(O)R 7 , —C(O)NR 7 R 7 , —NO 2 , —OR 7 , —SR 7 —NR 7 R 7 , —NR 7 C(O)OR 7 , —NR 7 C(O)R 7 , and a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O, which is C 1 -C 10  alkyl, C 1 -C 10  alkoxy, C 2 -C 10  alkenyl, C 1 -C 10  alkenoyl, C 3 -C 10  cycloalkyl having 0-3 heteroatoms selected from O, N and S, C 6 -C 14  aryl, C 3 -C 13  hetaryl having 1-3 heteroatoms selected from O, N and S, C 7 -C 24  alkaryl, C 7 -C 24  aralkyl, C 4 -C 23  alkheteroaryl having 1-3 heteroatoms selected from O, N and S, and optionally substituted by one or more substituents are selected from the group consisting of —CN, —CO 2 R 7 , —COR 7 , —C(O)NR 7 R 7 , —OR 7 , —SR 7 , —NO 2 , —NR 7 R 7 , —NR 7 C(O)R 7 , and —NR 7 C(O)OR 7 , with R 7  as defined above where R g  is C 1-10  alkyl; —CN, —CO 2 R d , —OR d , —SR d , —NO 2 , —C(O)R e , NR d R e , —NR d C(O)OR e  and —NR d C(O)R e , and R d  and R e  are independently selected from the group consisting of hydrogen, C 1-10 , alkyl, C 1-10  alkoxy, C 3-10  cycloalkyl having 0-3 heteroatoms selected from O, N and S, C 6-12  aryl, C 3 -C 12  hetaryl with 1-3 heteroatoms selected from O, N and S and C 7 -C 24  aralkyl, C 7 -C 24  alkaryl, up to per halo substituted C 1 -C 10  alkyl, up to per halo substituted C 3 -C 10  cycloalkyl having 0-3 heteroatoms selected from O, N and S, up to per halo substituted C 6 -C 14  aryl, up to per halo substituted C 3 -C 12  hetaryl having 1-3 heteroatoms selected from O, N, and S, halo substituted C 7 -C 24  alkaryl up to per halo alkaryl, or up to per halo substituted C 7 -C 24  aralkyl.  
 
     
     
         69 . A compound of Formula I:  
         A-D-B  (I)  
       or a pharmaceutically acceptable salt thereof, wherein 
 D is —NH—C(O)—NH—,  
 A is a substituted moiety of up to 40 carbon atoms of the formula: -L-(M-L 1 ) q , where L is a substituted or unsubstituted phenyl or pyridinyl moiety bound directly to D, L 1  comprises a substituted phenyl moiety, M is —O— and  
 B is a substituted or unsubstituted phenyl group bound directly to D,  
 wherein L 1  is substituted by —C(O)R x ,  
 R x  is NR a R b  where R a  and R b  are  
 a) independently hydrogen,  
 a moiety, which is C 1 -C 10  alkyl, C 1 -C 10  alkoxy, C 3-10  cycloalkyl, C 2-10  alkenyl, C 1-10  alkenoyl, C 6-12  aryl, C 3-12  hetaryl having 1-3 heteroatoms selected from O, N and S, C 3-12  cycloalkyl having 0-3 heteroatoms selected from N, S and O, C 7-24  aralkyl, or C 7 -C 24  alkaryl, and optionally substituted by halogen, hydroxy and carbon based substituents which are —C 1-10  allyl, C 3-12  cycloalkyl having 0-3 heteroatoms selected from O, S and N, C 3-12  hetaryl having 1-3 heteroatoms selected from N, S and O, C 1-10  alkoxy, C 6-12  aryl, C 1-6  halo substituted alkyl up to per halo alkyl, C 6 -C 12  halo substituted aryl up to per halo aryl, C 3 -C 12  halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C 3 -C 12  hetaryl up to per halo hetaryl, halo substituted C 7 -C 24  aralkyl up to per halo aralkyl, or halo substituted C 7 -C 24  alkaryl up to per halo alkaryl, and —C(O)R g ,  
 where B is substituted, L is substituted or L 1  is additionally substituted, the substituents are selected from the group consisting of halogen, up to per-halo, and Wn, where n is 0-3;  
 wherein each W is independently selected from the group consisting of —CN, —CO 2 R 7 , —C(O)NR 7 R 7 , —C(O)—R 7 , —NO 2 , —OR 7 , —SR 7 , —NR 7 R 7 , —NR 7 C(O)OR 7 , —NR 7 C(O)R 7 , -Q-Ar, and moieties which are C 1 -C 10  alkyl, C 1 -C 10  alkoxy, C 2 -C 10  alkenyl, C 1 -C 10  alkenoyl, C 3 -C 10  cycloalkyl having 0-3 heteroatoms selected from O, S and N, C 6 -C 14  aryl, C 7 -C 24  alkaryl, C 7 -C 24  aralkyl, C 3 -C 12  heteroaryl having 1-3 heteroatoms selected from O, N and S, or C 4 -C 23  alkheteroaryl having 1-3 heteroatoms selected from O, N and S, and optionally substituted by one or more substituents independently selected from the group consisting of —CN, —CO 2 R 17 , —C(O)R 7 , —C(O)NR 7 R 7 , —OR 7 , —SR 7 , —NR 7 R 7 , —NO 2 , —NR 7 C(O)R 7 , —NR 7 C(O)OR 7  and halogen up to per-halo; with each R 7  independently selected from H or a moiety which is C 1 -C 10  alkyl, C 1 -C 10  alkoxy, C 2 -C 10  alkenyl, C 1 -C 10  alkenoyl, C 3 -C 10  cycloalkyl having 0-3 heteroatoms selected from O, S and N, C 6 -C 14  aryl, C 3 -C 13  hetaryl having 1-3 heteroatoms selected from O, N and S, C 7 -C 14  alkaryl, C 7 -C 24  aralkyl, or C 4 -C 23  alkheteroaryl having 1-3 heteroatoms selected from O, N and S,  
 wherein Q is —O—, —S—, —N(R 7 )—, —(CH 2 ) m —, —C(O)—, —CH(OH)—, —(CH 2 ) m O—, —(CH 2 ) m S—, —(CH 2 ) m N(R 7 )—, —O—(CH 2 ) m —CHX a —, —CX a   2 —, —S—(CH 2 ) m — and —N(R 7 )(CH 2 ) m —, where m=1-3, and X a  is halogen;  
 Ar is phenyl or pyridinyl which is optionally substituted by halogen, up to per-halo, and optionally substituted by Z n1 , wherein n1 is 0 to 3 and each Z is independently selected from the group consisting of —CN, —CO 2 R 7 , —C(O)R 7 , —C(O)NR 7 R 7 , —NO 2 , —OR 7 , —SR 7 —NR 7 R 7 , —NR 7 C(O)OR 7 , —NR 7 C(O)R 7 , and a moiety which is C 1 -C 10  alkyl, C 1 -C 10  alkoxy, C 2 -C 10  alkenyl, C 1 -C 10  alkenoyl, C 3 -C 10  cycloalkyl having 0-3 heteroatoms selected from O, N and S, C 6 -C 14  aryl, C 3 -C 13  hetaryl having 1-3 heteroatoms selected from O, N and S, C 7 -C 24  alkaryl, C 7 -C 24  aralkyl, or C 4 -C 23  alkheteroaryl having 1-3 heteroatoms selected from O, N and S, and optionally substituted by one or more substituents selected from the group consisting of —CN, —CO 2 R 7 , —COR 7 , —C(O)NR 7 R 7 , —OR 7 , —OR 7 , —NO 2 —NR 7 R 7 , —NR 7 C(O)R 7 —, and —NR 7 C(O)OR 7 ; and where R g  is C 1-10  alkyl; —CN, —CO 2 R d , —OR d , —SR d , —NO 2 , —C(O)R e , —NR d R e , —NR d C(O)OR e , and —NR d C(O)R e , and R d  and R e  are independently selected from the group consisting of hydrogen, C 1-10 , alkyd, C 1-10  alkoxy, C 3-10  cycloalkyl having 0-3 heteroatoms selected from O, N and S, C 6-12  aryl, C 3 -C 12  hetaryl with 1-3 heteroatoms selected from O, N and S and C 7 -C 24  aralkyl, C 7 -C 24  alkaryl, up to per halo substituted C 1 -C 10  alkyl, up to per halo substituted C 3 -C 10  cycloalkyl having 0-3 heteroatoms selected from O, N and S, up to per halo substituted C 6 -C 14  aryl, up to per halo substituted C 3 -C 12  hetaryl having 1-3 heteroatoms selected from O, N, and S, halo substituted C 7 -C 24  alkaryl up to per halo alkaryl, or up to per halo substituted C 7 -C 24  aralkyl.  
 
     
     
         70 . A compound as in  claim 68  wherein the cyclic structures of B and L bound directly to D have hydrogen substituents in the ortho position.  
     
     
         71 . A compound as in  claim 69  wherein the cyclic structures of B and L bound directly to D have hydrogen substituents in the ortho position.  
     
     
         72 . A compound as in  claim 68  wherein substituents for B and L and additional substituents for L 1 , are selected from the group consisting of C 1 -C 10  alkyl up to per halo substituted C 1 -C 10  alkyl, CN, OH, halogen, C 1 -C 10  alkoxy and up to per halo substituted C 1 -C 10  alkoxy.  
     
     
         73 . A compound as in  claim 69  wherein substituents for B and L and additional substituents for L 1 , are selected from the group consisting of C 1 -C 10  alkyl up to per halo substituted C 1 -C 10  alkyl, CN, OH, halogen, C 1 -C 10  alkoxy and up to per halo substituted C 1 -C 10  alkoxy.  
     
     
         74 . A compound of  claim 68  wherein R a  and R b  are independently hydrogen and C 1-6  alkyl.  
     
     
         75 . A compound of  claim 69  wherein R a  and R b  are independently hydrogen and C 1-6  alkyl, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.  
     
     
         76 . A pharmaceutically acceptable salt of a compound of  claim 68  which is 
 a) a basic salt of an organic acid or inorganic acid which is hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid; or    b) an acid salt of an organic or inorganic base containing an alkali metal cation, an alkaline earth metal cation, an ammonium cation, an aliphatic substituted ammonium cation or an aromatic substituted ammonium cation.    
     
     
         77 . A pharmaceutically acceptable salt of a compound of  claim 69  which is 
 a) a basic salt of an organic acid or inorganic acid which is hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid; or    b) an acid salt of an organic or inorganic base containing an alkali metal cation, an alkaline earth metal cation, an ammonium cation, an aliphatic substituted ammonium cation or an aromatic substituted ammonium cation.    
     
     
         78 . A pharmaceutical composition comprising a compound of  claim 68  and a physiologically acceptable carrier.  
     
     
         79 . A pharmaceutical composition comprising a compound of  claim 69  and a physiologically acceptable carrier.  
     
     
         80 . A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administering a compound of  claim 68 .  
     
     
         81 . A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administering a compound of  claim 69 .  
     
     
         82 . A compound of Formula I:  
         A-D-B  (I)  
       or a pharmaceutically acceptable salt thereof, wherein 
 D is —NH—C(O)—NH—,  
 A is a substituted moiety of the formula:  
   -L-M-L 1 ,  
 wherein L is  
 phenyl, optionally substituted with 1-3 substituents independently selected from the group consisting of C 1 -C 5  linear or branched alkyl, C 1 -C 5  linear or branched haloalkyl up to perhalo, C 1 -C 3  alkoxy, C 1 -C 3  haloalkoxy up to per haloalkoxy, hydroxy, amino, C 1 -C 3  alkylamino, C 1 -C 6  dialkylamino, halogen, cyan-o, and nitro;  
 L 1  comprises a substituted cyclic moiety which is  
 phenyl, optionally substituted with 1-3 substituents independently selected from the group consisting of R 7 , OR 7 , NR 7 R 7′ , C(O)R 7 , C(O)OR 7 , C(O)NR 7 R 7 , NR 7 C(O)R 7′ , NR 7 C(O)OR 7′ , halogen, cyano and nitro;  
 and  
 wherein R x  is R z  or NR a R b  and R a  and R b  are,  
 independently, R z    
 M is —O— 
 B is  
 (i) phenyl, optionally substituted with 1-3 substituents independently selected from the group consisting of R 7 , OR 7 , NR 7 R 7′ , C(O)R 7 , C(O)OR 7 , C(O)NR 7 R 7′ , NR 7 C(O)R 7′ , NR 7 C(O)OR 7′  halogen, cyano, and nitro; or  
 (ii) pyridinyl optionally substituted with 1-3 substituents independently selected from the group consisting of R 7 , OR 7 , NR 7 R 7′ , C(O)R 7 , C(O)OR 7 , C(O)NR 7 R 7′ , NR 7 C(O)R 7′ , NR 7 C(O)OR 7′ , halogen, cyano, and nitro; and  
 each R 7 , R 7′ , R z  and R f  is independently  
 (a) hydrogen,  
 (b) C 1 -C 6  linear, branched, or cyclic alkyl, optionally substituted with 1-3 substituents independently selected from the group consisting of C 1 -C 5  linear or branched alkyl, up to perhalo substituted C 1 -C 5  linear or branched alkyl, C 1 -C 3  alkoxy and hydroxy;  
 (c) C 1 -C 6  alkoxy, optionally substituted with 1-3 substituents independently selected from the group consisting of C 1 -C 5  linear or branched alkyl, up to perhalo substituted C 1 -C 5  linear or branched alkyl, C 1 -C 3  alkoxy, hydroxy and halogen;  
 (d) phenyl, optionally substituted with 1-3 substituents independently selected from the group consisting of C 1 -C 5  linear or branched alkyl, up to perhalo substituted C 1 -C 5  linear or branched alkyl, C 1 -C 3  alkoxy, hydroxy and halogen,  
 (e) 5-6 membered monocyclic heteroaryl having 1-4 heteroatoms selected from the group consisting of O, N and S or 8-10 membered bicyclic heteroaryl having 1-6 hetero atoms selected from the group consisting of O, N and S, optionally substituted with 1-3 substituents independently selected from the group consisting of C 1 -C 5  linear or branched alkyl, up to perhalo substituted C 1 -C 5  linear or branched alkyl, C 1 -C 3  alkoxy, hydroxy and halogen,  
 (f) C 1 -C 3  alkyl-phenyl, optionally substituted with 1-3 substituents independently selected from the group consisting of C 1 -C 5  linear or branched alkyl, up to perhalo substituted C 1 -C 5  linear or branched alkyl, C 1 -C 3  alkoxy, hydroxy and halogen; and  
 (g) up to per-halo substituted C 1 -C 5  linear, branched or cyclic alkyl, and where not per-halo substituted, optionally substituted with 1-3 substituents independently selected from the group consisting of C 1 -C 5  linear or branched alkyl, up to perhalo substituted C 1 -C 5  linear or branched alkyl, C 1 -C 3  alkoxy and hydroxy.  
 
     
     
         83 . A compound of  claim 82  wherein the substituents of the substituted structures of L are selected from the group consisting of methyl, trifluoromethyl, ethyl, n-propyl, n-butyl, n-pentyl, i-propyl, t-butyl, methoxy, ethoxy, propoxy, Cl, Br, F, cyano, nitro, hydroxy, amino, methylamino, dimethylamino, ethylamino and diethylamino.  
     
     
         84 . A compound of  claim 82  wherein the substituents of the substituted structures of B and L 1  are independently selected from the group consisting of methyl, trifluoromethyl, ethyl, n-propyl, n-butyl, n-pentyl, isopropyl, tert-butyl, sec-butyl, isobutyl, cyclopropyl, cyclobutyl, cyclopentyl, methoxy, ethoxy, propoxy, Cl, Br and F, cyano, nitro, hydroxy, amino, methylamino, dimethylamino, ethylamino and diethylamino.  
     
     
         85 . A compound as in  claim 82  wherein B, L and L 1  follow one of the following of combinations: 
 B3 phenyl, L=phenyl and L 1  is phenyl,    B=pyridinyl, L=phenyl and L 1  is phenyl,    B=pyridinyl, L=phenyl and L 1  is pyridinyl,    
     
     
         86 . A pharmaceutical composition for the treatment of a cancerous cell growth comprising a compound of  claim 82  or a pharmaceutically acceptable salt of a compound of formula I and a physiologically acceptable carrier.  
     
     
         87 . A pharmaceutical composition for the treatment of a cancerous cell growth as in  claim 86  wherein the pharmaceutically acceptable salt is 
 a) a basic salt of an organic acid or an inorganic acid which is hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid; or    b) an acid salt of an organic or inorganic base containing an alkali metal cation, an alkaline earth metal cation, an ammonium cation, an aliphatic substituted ammonium cation or an aromatic substituted ammonium cation.