5-O-mycaminosyltylonide derivatives

Abstract

There are described novel 5-O-mycaminosyltylonide derivatives and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described are a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeutically-effective amount of a compound of the invention, and processes for the preparation of such compounds.

What is claimed is:  
     
         1 . A compound represented by the Formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 A is selected from the group consisting of:  
 (1) —CHO or a protected aldehyde;  
 (2) —CN;  
 (3) —CH═N—NR 5 R 6 , wherein R 5  and R 6  are each independently selected from the group consisting of: 
 (a) hydrogen,  
 (b) C 1 -C 6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic,  
 (c) C 2 -C 6 -alkenyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic,  
 (d) C 2 -C 6 -alkynyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic, and  
 (e) R 5  and R 6  taken together with the nitrogen atom to which they are connected form a 3- to 7-membered ring which may optionally contain one or more heterofunctions selected from the group consisting of: —O—, —NH—, —N(C 1 -C 6 -alkyl)-, —N(aryl)—, —N(heteroaryl)-, —S—, —S(O)— and —S(O) 2 —;  
 
 (4) —CH═N—OR 5 , wherein R 5  is as previously defined;  
 (5) —CH 2 X, wherein X is selected from the group consisting of: 
 (a) hydroxy or protected hydroxy;  
 (b) halogen;  
 (c) —NR 5 R 6 , wherein R 5  and R 6  are as previously defined;  
 (d) —NR 5 C(O)—R 7 , where R 5  is as previously defined and R 7  is selected from the group consisting of: 
 i. hydrogen;  
 ii. C 1 -C 6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic;  
 iii. C 2 -C 6 -alkenyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic;  
 iv. C 2 -C 6 -alkynyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic;  
 v. aryl;  
 vi. substituted aryl;  
 vii. heterocyclic; and  
 viii. substituted heterocyclic;  
 
 (e) —NR 5 C(O)—NR 6 R 7 , where R 5 , R 6 , and R 7  are as previously defined;  
 (f) —NR 5 —NR 6 R 7 , where R 5 , R 6  and R 7  are as previously defined;  
 (g) —NR 5 —NR 6 C(O)—R 7 , where R 5 , R 6  and R 7  are as previously defined;  
 (h) —S(O) n —R 8 , where R 8  is selected from the group consisting of: aryl, substituted aryl, heterocyclic and substituted heterocyclic, where n=0, 1 or 2;  
 (i) —S(O) n —(C 1 -C 6 -alkyl), optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic, where n is as previously defined;  
 (j) —S(O) n —(C 2 -C 6 -alkenyl), optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic, where n is as previously defined;  
 (k) —S(O) n —(C 2 -C 6 -alkynyl), optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic, where n is as previously defined; and  
 (l) —O-M-Y, where M is: 
 i. absent,  
 ii. —C(O)—,  
 iii. —C(O)N(R 5 )—, where R 5  is as previously defined,  
 iv. C 1 -C 6 -alkyl-N(R 5 )—Y, where R 5  is as previously defined,  
 v. C 2 -C 6 -alkenyl-N(R 5 )—Y, where R 5  and Y are as previously defined, or  
 vi. C 2 -C 6 -alkynyl-N(R 5 )—Y, where R 5  and Y are as previously defined, and Y is:  
 i. hydrogen,  
 ii. C 1 -C 6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of halogen, —OR 5 , aryl, substituted aryl, heterocyclic and substituted heterocyclic, where R 5  is as previously defined,  
 iii. C 2 -C 6 -alkenyl, optionally substituted with one or more substituents selected from the group consisting of halogen, —OR 5 , aryl, substituted aryl, heterocyclic and substituted hetreocyclic, where R 5  is as previously defined,  
 iv. C 2 -C 6 -alkynyl, optionally substituted with one or more substituents selected from the group consisting of halogen, —OR 5 , aryl, substituted aryl, heterocyclic and substituted heterocyclic, where R 5  is as previously defined,  
 v. aryl,  
 vi. substituted aryl,  
 vii. heterocyclic, or  
 viii. substituted heterocyclic; and  
 
 
 (6) heterocyclic or substituted heterocyclic;  
 B is selected from the group consisting of:  
 (1) —CHO or a protected aldehyde;  
 (2) —CN;  
 (3) —CH═N—NR 5 R 6 , wherein R 5  and R 6  are as previously defined;  
 (4) —CH═N—OR 5 , wherein R 5  is as previously defined;  
 (5) —CH 2 Z, wherein Z is selected from the group consisting of: 
 a. halogen;  
 b. —NR 5 C(O)—R 7 , where R 5  and R 7  are as previously defined;  
 c. —NR 5 C(O)—NR 6 R 7 , where R 5 , R 6 , and R 7  are as previously defined;  
 d. —NR 5 —NR 6 R 7 , where R 5 , R 6  and R 7  are as previously defined;  
 e. —NR 5 —NR 6 C(O)—R 7 , where R 5 , R 6  and R 7  are as previously defined;  
 f. —S(O) n —R 8 , where R 8  and  n  are as previously defined;  
 g. —S(O) n —(C 1 -C 6 -alkyl), optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic, where n is as previously defined;  
 h. —S(O) n —(C 2 -C 6 -alkenyl), optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic, where n is as previously defined;  
 i. —S(O) n —(C 2 -C 6 -alkynyl), optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic, where n is as previously defined; and  
 j. —NR 9 R 10 , where R 9  and R 10  are each independently selected from the group consisting of: 
 i. hydrogen;  
 ii. C 1 -C 6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, —O—R 5  and —NR 5 R 6,  where R 5  and R 6  are as previously defined;  
 iii. C 2 -C 6 -alkenyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —O—R 5  and —NR 5 R 6 , where R 5  and R 6  are as previously defined;  
 iv. C 2 -C 6 -alkynyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, O—R 5  and NR 5 R 6 , where R 5  and R 6  are as previously defined; and  
 v. —W—R 11 , where W is selected from the group consisting of: 
 1. —C(O)—;  
 2. —C(O)O—;  
 3. —C(S)—;  
 4. —C(S)—S—;  
 5. —C(S)—O—;  
 6. —C(S)—NR 5 , where R 5  is as previously defined;  
 7. —C(O)NR 5 , where R 5  is as previously defined;  
 8. —C(═NR 5 )—O—, where R 5  is as previously defined; and  
 9. —C(═NR 5 )—NR 6 , where R 5  and R 6  are as previously defined, and where R 11  is selected from the group consisting of:  
  a. hydrogen;  
  b. C 1 -C 6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic;  
  C. C 2 -C 6 -alkenyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic;  
  d. C 2 -C 6 -alkynyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic;  
 
 vi. R 9  and R 10  taken together with the nitrogen atom they are attached to represent the carbon or hetero atoms necessary to form a heterocyclic or substituted heterocyclic moiety; and  
 vii. R 9  and R 10 , taken together with the nitrogen atom they are attached to form a 4 to 8 membered ring which contains one or more W moieties, and optionally may contain one or more heteromoieties selected from the group consisting of —O—, —S—, —S(O) 2 — and —NR 5 —, where W and R 5  are as previously defined;  
 
 
 R 1  and R 2  are each independently selected from the group consisting of:  
 (1) hydrogen;  
 (2) hydroxy;  
 (3) protected hydroxy;  
 (4) —OC(O)—C 1 -C 12 -alkyl, optionally substituted with one or more substituents selected from the group consisting of halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, O—R5 and NR 5 R 6  where R 5  and R 6  are as previously defined;  
 (5) —O—R5, where R 5  is as previously defined;  
 (6) halogen;  
 (7) —NR 5 R 6 , where R 5  and R 6  are as previously defined; and  
 (8) R 1  and R 2  taken together are ═O;  
 R 3  is selected from the group consisting of:  
 (1) hydrogen;  
 (2) a hydroxy protecting group;  
 (3) —C(O)—C 1 -C 12 -alkyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —OR 5  and —NR 5 R 6 , where R 5  and R 6  are as previously defined;  
 (4) C 1 -C 6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —OR 5  and —NR 5 R 6 , where R 5  and R 6  are as previously defined;  
 (5) C 2 -C 6 -alkenyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —OR 5  and —NR 5 R 6 , where R 5  and R 6  are as previously defined; and  
 (6) C 2 -C 6 -alkynyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —OR 5  and —NR 5 R 6 , where R 5  and R 6  are as previously defined;  
 R 4  is -M-Y, where M and Y are as previously defined; and  
 R p  is hydrogen or a hydroxy protecting group.  
 
     
     
         2 . A compound according to  claim 1  where R 3  is selected from the group consisting of: 
 (1) C 1 -C 6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —O—R 5  and —NR 5 R 6 , where R 5  and R 6  are as defined in  claim 1;   
 (2) C 2 -C 6 -alkenyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —O—R 5  and —NR 5 R 6 , where R 5  and R 6  are as previously defined; and  
 (3) C 2 -C 6 -alkynyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —O—R 5  and —NR 5 R 6 , where R 5  and R 6  are as previously defined.  
 
     
     
         3 . A compound according to  claim 2 , where R 1  and R 2  taken together are ═O.  
     
     
         4 . A compound according to  claim 3 , where R 4  is hydrogen.  
     
     
         5 . A compound according to  claim 1 , where R 4  is selected from the group consisting of: 
 (1) C 1 -C 6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of: halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —O—R 5  and —NR 5 R 6 , where R 5  and R 6  are as defined in  claim 1;     (2) C 2 -C 6 -alkenyl, optionally substituted with one or more substituents selected from the group consisting of halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —O—R 5  and —NR 5 R6, where R 5  and R 6  are as previously defined; and    (3) C 2 -C 6 -alkynyl, optionally substituted with one or more substituents selected from the group consisting of halogen, aryl, substituted aryl, heterocyclic, substituted heterocyclic, —O—R 5  and —NR 5 R 6 , where R 5  and R 6  are as previously defined.    
     
     
         6 . A compound according to  claim 5 , where R 1  and R 2  taken together are ═O.  
     
     
         7 . A compound according to  claim 6 , where R 3  is hydrogen.  
     
     
         8 . A compound as defined in  claim 1  which is selected from the group consisting of: 
 Compound of Formula I: A=-CHO, B═—CH 2 —N(CH 3 ) 2 , R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═H and R p ═H;  
 Compound of Formula I: A=-CHO, B═—CH 2 —NH—CH 2 CH 2 Phenyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═H and R p ═H;  
 Compound of Formula I: A=-CHO, B═—CH 2 —N(CH 3 )—CH 2 CH 2 Phenyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═H and R p ═H;  
 Compound of Formula I: A=-CHO, B═—CH 2 —NH—CH 2 CH 2 —(2-pyridyl) R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═H and R p ═H;  
 Compound of Formula I: A=-CHO, B═—CH 2 -4-morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═H and R p ═H;  
 Compound of Formula I: A=-CHO, B═—CH 2 -1 -imidazolyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═H and R p ═H;  
 Compound of Formula I: A=-CHO, B═—CH 2 —N(CH 3 ) 2 , R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(5-pyrimidyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(5-pyrimidyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(5-pyrimidyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CCCH 2 -(phenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCHCH 2 -(phenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 CH 2 -(phenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CCCH 2 -(4-fluorophenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCHCH 2 -(4-fluorophenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 CH 2 -(4-fluorophenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CCCH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCHCH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 CH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(2-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(2-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(2-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(3-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(3-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B=morpholyl, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(3-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(5-pyrimidyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(5-pyrimidyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(5-pyrimidyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CCCH 2 -(phenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCHCH 2 -(phenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 CH 2 -(phenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CCCH 2 -(4-fluorophenyl) and R p ═H;  
 Compound of Formula 1: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCHCH 2 -(4-fluorophenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 CH 2 -(4-fluorophenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CCCH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCHCH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 CH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(2-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(2-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(2-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(3-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(3-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CH 2 F, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(3-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(5-pyrimidyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(5-pyrimidyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(5-pyrimidyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CCCH 2 -(phenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCHCH 2 -(phenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 CH 2 -(phenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CCCH 2 -(4-fluorophenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCHCH 2 -(4-fluorophenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 CH 2 -(4-fluorophenyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CCCH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCHCH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 CH 2 -(3-quinolyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(2-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(2-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(2-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CC-(3-pyridyl) and R p ═H;  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CHCH-(3-pyridyl) and R p ═H; and  
 Compound of Formula I: A=CHO, B═CN, R 1  and R 2  taken together are ═O, R 3 ═H, R 4 ═CH 2 CH 2 CH 2 -(3-pyridyl) and R p ═H.  
 
     
     
         9 . A pharmaceutical composition for treating bacterial infections comprising a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt, ester or prodrug thereof in combination with a pharmaceutically acceptable carrier.  
     
     
         10 . A method for treating bacterial infections comprising administering to an animal in need of such treatment a pharmaceutical composition comprising a pharmaceutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt, ester or prodrug thereof.  
     
     
         11 . A process for preparing a compound represented by Formula I as defined in  claim 1  comprising: 
 (a) reacting a compound represented by the formula:  
                     
 wherein R P   2  is a hydroxy protecting group, with:  
 i. an acetalating agent at a pH between 1 to 4 in an alcoholic solvent; and  
 ii. treating with a silylating agent, optionally with the addition of a catalyst in an aprotic solvent at a temperature between 0° C. to 50° C. for 1 to 48 hours to provide a compound represented by the Formula:  
                     
 wherein R P   1 , R P   2 , R P   3  and R P   4  are hydroxy protecting groups, and R′ and R″ are each C 1 -C 6 -alkyl or when taken together are —CH 2 CH 2 — or —CH 2 CH 2 CH 2 —;  
 (b) treating the compound from step (a) with an acid in an organic solvent at a temperature between 0° C. and 50° C. for 1-24 hours to provide a compound represented by the formula:  
                     
 wherein R P   1 , R P   2 , R P   3 , R′ and R″ are as previously defined;  
 (c) reacting the compound from step (b) with an alkylating agent represented by the formula R 4 X, wherein X is a halogen or sulphonyl group and R 4  is as defined in  claim 1 , in the presence of a base in an aprotic solvent at a temperature between −20° C. to 60° C. optionally in the presence of water and a phase transfer catalyst, and then treating with an acid in an organic solvent at a temperature between room temperature to 100° C. for 1 to 48 hours to provide a compound represented by the formula:  
                     
 wherein R P   2 , R P   3 , R 4 , R′ and R″ are as previously defined;  
 (d) treating the compound from step (c) with triphenylphosphine and a halogenating agent or with a sulfonic anhydride or sulfonyl chloride in an aprotic organic solvent at a temperature between −78° C. and 50° C. for 30 minutes to 48 hours, optionally in the presence of an amine base and a catalyst, to provide a compound represented by the formula:  
                     
 where L is selected from the group consisting of chlorine, bromine, iodine, mesylate and tosylate and R P   2 , R P   3 , R 4 , R′ and R″ are as previously defined; and  
 (e) treating the compound from step (d) with an amine of the formula NHR 5 R 6 , wherein R 5  and R 6  are as defined in  claim 1 , at a temperature from 0° C. to 100° C. for 1 to 24 hours, optionally deprotecting the product by: 
 i. treating with an aqueous acid in an organic solvent at a temperature from 0° C. to 100° C. for 1 to 24 hours; and  
 ii. stirring in methanol at a temperature between room temperature and reflux temperature for 4 to 24 hours;  
 to provide a compound represented by Formula I wherein A is —CHO, B is —CH 2 —NR 5 R 6 , R 1  and R 2  together are O, R 3  is H, R p  is H, and R 4  is as defined in  claim 1 .  
 
 
     
     
         12 . A process for preparing a compound represented by Formula I, as defined in  claim 1  comprising: 
 (a) reacting a compound represented by the Formula:  
                     
 where Ac is —COCH 3 , in an aprotic organic solvent with a sulfonic anhydride or sulphonyl halide in the presence of an amine base, optionally with a catalyst, between 0° C. and room temperature for 30 minutes to two hours and treating the resulting product with sodium iodide, at a temperature between 0° C. to 100° C. for 1 to 24 hours, to provide a compound represented by the formula:  
                     
 where Ac is as previously defined; and  
 (b) treating the compound from step (a) with an amine of the formula NHR 5 R 6 , where R 5  and R 6  are as defined in  claim 1 , at a temperature from 0° C. to 100° C. for 1 to 24 hours, optionally deprotecting the product by: 
 i. treating with an aqueous acid in an organic solvent at a temperature from 0° C. to 100° C. for 1 to 24 hours; and  
 ii. stirring in methanol at a temperature between room temperature and reflux temperature;  
 
 to provide a compound represented by Formula I where A is —CHO, B is —CH 2 —NR 5 R 6 , R 1  and R 2  taken together are O, R 3  is H, R P  is H, and R 4  is H.  
 
     
     
         13 . A process for preparing a compound represented by the formula:  
       
         
           
           
               
               
           
         
       
       wherein R is aryl, substituted aryl, heteroaryl, or substituted heteroaryl, R P   2  and R P   3  are each independently hydrogen or a hydroxy protecting group and R 5  and R 6  are as defined in  claim 1 , comprising: 
 (a) reacting a compound represented by the formula:  
                     
 wherein R P   1 , R P   2  and R P   3  are hydroxy protecting groups, and R′ and R″ are each C 1 -C 6 -alkyl or when taken together are —CH 2 CH 2 — or —CH 2 CH 2 CH 2 —, with a propargyl halide and optionally reducing the product with a borane or stannane reagent to give a vinyl borane or vinyl stannane derivative represented by the formula:  
                     
 wherein M is hydrogen, B(OH) 2  or SnBu 3  and R P   1 , R P   2 , R P   3 , R′ and R″ are as previously defined;  
 (b) reacting the compound from step (a) with a compound represented by the formula R—X wherein R is aryl, substituted aryl, heteroaryl, or substituted heteroaryl and X is a halide or triflate, in the presence of a palladium catalyst to give a compound represented by the formula:  
                     
 wherein R, R P   1 , R P   2 , R P   3 , R′ and R″ are as previously defined; and  
 (c) treating the compound from step (b) with an organic acid in an organic solvent at a temperature between room temperature to 100° C. for 1-48 hours to provide a compound represented by the formula:  
                     
 wherein R, R P   2 , R P   3 , R′ and R″ are as previously defined;  
 (d) treating the compound from step (c) with triphenylphosphine and a halogenating agent or with a sulfonic anhydride or sulfonyl chloride in an aprotic organic solvent at a temperature between −78° C. to 50° C. for 30 minutes to 48 hours, optionally in the presence of an amine base and a catalyst, to provide a compound represented by the formula:  
                     
 where L is chlorine, bromine, iodine, mesylate or tosylate and R P   2 , R P   3 , R, R′ and R″ are as previously defined; and  
 (e) treating the compound from step (d) with an amine of the formula NHR 5 R 6 , where R 5  and R 6  are as defined in  claim 1 , at a temperature from 0° C. to 100° C. for 1 to 24 hours, optionally deprotecting the product by: 
 i. treating with an aqueous acid in an organic solvent at a temperature from 0° C. to 100° C. for 1 to 24 hours; and  
 ii. stirring in methanol at a temperature between room temperature and reflux temperature for 4 to 24 hours;  
 
 to provide a compound represented by the formula:  
                     
 wherein R p   2 , R p   3 , R, R 5  and R 6  are as previously defined.  
 
     
     
         14 . A process for preparing a compound represented by the formula:  
       
         
           
           
               
               
           
         
       
       wherein R is aryl, substituted aryl, heteroaryl, or substituted heteroaryl, R p   2 , and R p   3  are each independently hydrogen or a hydroxy protecting group, and R 5  and R 6  are as defined in  claim 1 , comprising: 
 (a) reacting a compound represented by the formula:  
                     
 wherein R P   2  and R P   3  are hydroxy protecting groups, and R′ and R″ are each C 1 -C 6 -alkyl or when taken together are —CH 2 CH 2 — or —CH 2 CH 2 CH 2 — and R 5  and R 6  are as defined in  claim 1 , with a tert-butyl allyl carbonate or an aryl tert-butyl allyl carbonate in the presence of a palladium catalyst to provide a compound represented by the formula:  
                     
 wherein Z is hydrogen or R and where R, R 5 , R 6 , R P   2 , R P   3 , R′ and R″ are as previously defined;  
 (b) when Z is hydrogen, reacting the compound from step (a) with a compound represented by the formula R—X where R is aryl, substituted aryl, heteroaryl, or substituted heteroaryl and X is a halide or triflate, in the presence of a palladium catalyst to provide a compound represented by the formula:  
                     
 wherein R, R 5 , R 6 , R P   2 , R P   3 , R′ and R″ are as previously defined, optionally deprotecting the compound from step (a) or (b) by: 
 i. treating with an aqueous acid in an organic solvent at a temperature from 0° C. to 100° C. for 1 to 24 hours; and  
 ii. stirring in methanol at a temperature between room temperature and reflux temperature for 24 hours;  
 
 to provide a compound represented by the formula:  
                     
 where R, R 5 , R 6,  R P   2 , and R P   3  are as previously defined.  
 
     
     
         15 . A process for preparing a compound represented by Formula I, as defined in  claim 1 , comprising: 
 (a) reacting a compound represented by the formula:                          where B and R 4  are as defined in  claim 1 , R P   2  and R P   3  are each independently hydroxy protecting groups, and R′ and R″ are each C 1 -C 6 -alkyl or when taken together are —CH 2 CH 2 — or —CH 2 CH 2 CH 2 —, with tetrabutyl ammonium fluoride or hydrofluoric acid to provide a compound represented by the formula:                          wherein B, R 4 , R p   2 , R′ and R″ are as previously defined,    (b) reacting the compound from step (a) with an alkylating agent in the presence of a base in an aprotic solvent at a temperature between −20° C. and 60° C. to provide a compound of the formula:                          wherein R 3  is as defined in  claim 1  and B, R 4 , R P   2 , R′ and R″ are as previously defined,    optionally deprotecting the compound from step (b) by: 
 i. treating with an aqueous acid in an organic solvent at a temperature between 0° C. and 100° C. for 1 to 24 hours; and  
 ii. stirring in methanol at a temperature between room temperature and reflux temperature;  
   to provide a compound represented by Formula I wherein A is —CHO, R 1  and R 2  taken together are ═O, B, R 3  and R 4  are as defined in  claim 1  and R P  is hydrogen.    
     
     
         16 . A process for preparing a compound represented by Formula I, as defined in  claim 1 , comprising: 
 (a) reacting a compound represented by the formula:                          wherein B and R 4  are as defined in  claim 1 , R P   2  is a hydroxy protecting group, and R′ and R″ are each C 1 -C 6 -alkyl or when taken together are —CH 2 CH 2 — or —CH 2 CH 2 CH 2 —, with a propargyl halide and optionally reducing the product with a borane or stannane reagent to give a vinyl borane or vinyl stannane derivative represented by the Formula:                          wherein M is hydrogen, B(OH) 2  or SnBu 3  and B, R 4 , R P   2 , R′ and R″ are as previously defined;    (b) reacting the compound from step (a) with a compound represented by the formula R—X where R is aryl, substituted aryl, heteroaryl, or substituted heteroaryl, and X is a halide or triflate, in the presence of a palladium catalyst to give a compound represented by the formula:                          wherin F, R, R 4 , R P   2 , R′ and R″ are as previously defined,    optionally deproteting the compound from step (b) by: 
 i. treating with an aqueous acid in an organic solvent at a temperature between 0° C. and 100° C. for 1 to 24 hours; and  
 ii. stirring in methanol at a temperature between room temperature and reflux temperature;  
   to provide a compound represented by Formula I wherein A is —CHO, R 1  and R 2  taken together are O, R 3  is —CH 2 CHCH—R or —CH 2 C≡C—R, R is as previously defined, B and R 4  are as defined in  claim 1 , and R p  is hydrogen.    
     
     
         17 . A process for prepairing a compound represented by Formula I, as defined in  claim 1  comprising 
 (a) reacting a compound represented by the formula:  
                     
 wherein B and R 4  are as defined in  claim 1 , R P   2  is a hydroxy protecting group, and R′ and R″ are each C 1 -C 6 -alkyl or when taken together are —CH 2 CH 2 — or —CH 2 CH 2 CH 2 —, with an allyl halide to give a compound represented by the formula:  
                     
 wherein B, R 4 , R P   2 , R′ and R″ are as previously defined;  
 (b) reacting the compound from step (a) with a vinyl-R derivative, where R is aryl, substituted aryl, heroaryl or sustituted heteroaryl, using a ruthenium catalyst, to provide a compound represented by the formula:  
                     
 wherein B, R, R 4 ,R P   2 , R′ and R″ are as previously defined,  
 optionally deprotecting the compound from step (b) by: 
 i. treating with an aqueous acid in an organic solvent at a temperature between 0° C. and 100° C. for 1 to 24 hours; and  
 ii. stirring in methanol at a temperature between room temperature and reflux temperature;  
 
 to provide a compound represented by Formula I wherein A is —CHO, R 1  and R 2  taken together are O, R 3  is —CH 2 CHCH—R, R is as previously defined, B and R 4  are as defined in  claim 1 , and R P  is hydrogen.