US2010184975A1PendingUtilityA1
Compounds for alzheimber's disease

Assignee: MYRIAD PHARMACEUTICALS INCPriority: Oct 4, 2004Filed: Mar 8, 2010Published: Jul 22, 2010
Est. expiryOct 4, 2024(expired)· nominal 20-yr term from priority
Inventors:Rachel Slade Yevgeniya Klimova Robert J. Halter Ashantai J. Yungai Warren S. Weiner Ruth J. Walton Jon Adam Willardsen Mark B. Anderson Kenton Zavitz
C07D 409/04C07D 209/08C07D 231/12C07D 413/14C07D 403/04A61K 31/403C07D 491/10C07D 209/60C07D 405/14C07D 409/14C07D 401/14C07D 405/04C07D 413/04C07D 417/04C07D 403/10C07F 7/1804C07D 209/14C07D 401/04A61P 25/28C07D 209/10
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Claims
Abstract

The invention provides novel compounds useful for the treatment of neurodegenerative disorders including Alzheimer's disease and dementia. The compounds have a substituents chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═0)NH(C 1-3 alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3 alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl, where L is a linker.
Claims

exact text as granted — not AI-modified
1 . A compound of Formula I or II, pharmaceutically acceptable salts thereof, and pharmaceutical compositions having such compounds 
     
       
         
         
             
             
         
       
     
     wherein one or more of R1-R5 independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1 -3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl, and the others of R1-R5, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3  alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3  alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1 -3  alkyl) 2 , —S(═O) 2 NH(C 1 -3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;
 R6-R10, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring; 
 R11 is an optionally substituted phenyl or heterocyclic group; 
 R o  is chosen from alkyl and haloalkyl; and 
 L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, and wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl. 
 
   
   
       2 . The compound of  claim 1  wherein wherein R1-R5 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;
 one or more of R6-R9 are chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl; or two adjacent of R6-R9 can be taken together to form a 4-7 member substituted aryl or cycloalkyl ring wherein the substituent is chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1 -3  alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl; and the others of R6-R9, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;   R10 is chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3  alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(—O) 2 NH 2 , —S(—O) 2 N(C 1 -3  alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;   R o  is chosen from alkyl and haloalkyl;   R11 is an optionally substituted phenyl group; and   L is as defined above.   
   
   
       3 . The compound of  claim 1  wherein wherein R1-R9 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring;
 R10 is chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl; and   L is as defined above.   
   
   
       4 . The compound of  claim 1  wherein wherein R1-R10 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring;
 R11 is a phenyl ring substituted with one or more substituents independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3 alkyl), -L-S(—O) 2 NH 2 , -L-S(—O) 2 N(C 1-3 alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl and the others are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3  alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3  alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;   R o  is chosen from alkyl and haloalkyl; and   L is as defined above.   
   
   
       5 . The compound of  claim 1 , wherein R1-R9 and R11 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring;
 R10 is a phenyl ring substituted with one or more substituents independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3 alkyl), -L-S(—O) 2 NH 2 , -L-S(—O) 2 N(C 1-3  alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl; and   L is as defined above.   
   
   
       6 . The compound of  claim 1 , wherein R1-R9 and R11 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF, —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring;
 R10 is -L-R12 wherein L is as defined above; and   R12 is a phenyl ring substituted with one or more substituents independently chosen from of -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3 alkyl), -L-S(—O) 2 NH 2 , -L-S(O) 2 N(C 1-3 alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl; and   L is as defined above.   
   
   
       7 . The compound of  claim 1 , wherein R1-R10 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring;
 R11 is -L-R12 wherein L is as defined above; and   R12 is a phenyl ring substituted with one or more substituents independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3 alkyl), -L-S(—O) 2 NH 2 , -L-S(O) 2 N(C 1-3 alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl, and the others are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(—O) 2 (C 1-3 alkyl), —S(—O) 2 NH 2 , —S(—O) 2 N(C 1-3 alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;   R o  is chosen from alkyl and haloalkyl; and   L is as defined above.   
   
   
       8 . The compound of  claim 1  wherein R1-R9 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl ring;
 R10 and R11 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , and -L-R12; and   R12 is a phenyl ring substituted with one or more substituents independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3  alkyl), -L-S(—O) 2 NH 2 , -L-S(—O) 2 N(C 1-3  alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl; and   L is as defined above.   
   
   
       9 . A compound of Formula V or VI, a pharmaceutically acceptable salt thereof, and pharmaceutical compositions having such compounds 
     
       
         
         
             
             
         
       
       wherein one or more of R1-R5 is independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3  alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl; the others of R1-R5, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3  alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(—O) 2 (C 1-3 alkyl), —S(—O) 2 NH 2 , —S(O) 2 N(C 1-3  alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 , with the provision that R3 is not hydroxyl; 
       R o  is chosen from alkyl and haloalkyl; 
       L is as defined above; 
       R6-R10, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3  alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3  alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring; and 
       R11 is an optionally substituted phenyl group. 
     
   
   
       10 . A compounds of Formula IX or X, pharmaceutically acceptable salts thereof, and pharmaceutical compositions having the compounds 
     
       
         
         
             
             
         
       
     
     wherein one or more of R1-R11 are chosen from -L-R12, -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3 alkyl), -L-S(—O) 2 NH 2 , -L-S(O) 2 N(C 1-3  alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl; wherein R12 is a phenyl ring substituted with one or more substituents independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3  alkyl), -L-S(—O) 2 NH 2 , -L-S(—O) 2 N(C 1-3  alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl, and the others are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3  alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(—O) 2 (C 1-3 alkyl), —S(—O) 2 NH 2 , —S(O) 2 N(C 1-3  alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;
 R o  is chosen from alkyl and haloalkyl; 
 L is as defined above; and the others of R1-R11 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3  alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3  alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2;  and two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring. 
 
   
   
       11 . A compound of Formula XIII or XIV, pharmaceutically acceptable salts thereof, and pharmaceutical compositions having the compounds, 
     
       
         
         
             
             
         
       
     
     wherein L is as defined above or is selected from an optionally substituted, saturated or partially saturated cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and C 1-12  alkyl;
 R1-R10, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3  alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(—O)N(C 1-3 alkyl) 2 , —S(—O) 2 (C 1-3 alkyl), —S(—O) 2 NH 2 , —S(—O) 2 N(C 1-3  alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring; 
 R11 is chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl; 
 R o  is chosen from alkyl and haloalkyl; and 
 R12 is chosen from optionally substituted C 1-12  alkyl, phenyl, and C 3-7  cycloalkyl. 
 
   
   
       12 . The compound of  claim 1 , wherein one or more of R1-R5 is chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl, and the others of R1-R5, independent of one another, are chosen hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(—O) 2 (C 1-3 alkyl), —S(—O) 2 NH 2 , —S(O) 2 N(C 1-3 alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;
 R o  is chosen from alkyl and haloalkyl;   R6-R10, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl, heterocyclic, or cycloalkyl ring;   R11 is an optionally substituted heterocyclic group; and   L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl.   
   
   
       13 . The compound of  claim 1 , wherein R1-R5, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 NH 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;
 one or more of R6-R9 is independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl; or two adjacent of R6-R9 can be taken together to form an optionally substituted 4-7 member aryl, heterocyclic, or cycloalkyl ring substituted with one or more substituents independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl; and the others of R6-R9, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(—O) 2 (C 1-3 alkyl), —S(—O) 2 NH 2 , —S(—O) 2 N(C 1-3 alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;   R o  is chosen from alkyl and haloalkyl;   R11 is an optionally substituted heterocyclic group; and   L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl.   
   
   
       14 . The compound of  claim 1 , wherein R1-R9 are independently chosen hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3  alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form an optionally substituted C 4-7  member aryl, heterocyclic, or cycloalkyl ring;
 R10 is chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl;   R11 is an optionally substituted heterocyclic group; and   L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl.   
   
   
       15 . The compound of  claim 1 , wherein R1-R10, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl, heterocyclic, or cycloalkyl ring;
 R11 is a heterocyclic group with one or more substituents independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3 alkyl), -L-S(—O) 2 NH 2 , -L-S(O) 2 N(C 1-3 alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl; and   L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl.   
   
   
       16 . The compound of  claim 1 , wherein R1-R9 and R11 independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl, heterocyclic, or cycloalkyl ring;
 R10 is a heterocyclic group with one or more substituents independently chosen -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl; and   L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl.   
   
   
       17 . The compound of  claim 1 , wherein R1-R9 and R11 independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl, heterocyclic, or cycloalkyl ring;
 R10 is -L-R12;   R12 is a heterocyclic group with one or more substituents chosen from-L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl; and   L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, (CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl.   
   
   
       18 . The compound of  claim 1 , wherein R1-R9 and R11 independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl, heterocyclic, or cycloalkyl ring;
 R10 is a heterocyclic group with one or more substituents independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3 alkyl), -L-S(—O) 2 NH 2 , -L-S(—O) 2 N(C 1-3 alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl; and   L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl.   
   
   
       19 . The compound of  claim 1 , wherein R1-R9, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl, heterocyclic, or cycloalkyl ring;
 R10 and R11 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(—O) 2 NH 2 , —S(O) 2 (C 1-3 alkyl), —S(—O) 2 N(C 1-3 alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , and -L-R12;   R12 is a heterocyclic group with one or more substituents independently chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3 alkyl), -L-S(—O) 2 NH 2 , -L-S(—O) 2 N(C 1-3 alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;   R o  is chosen from alkyl and haloalkyl; and   L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl.   
   
   
       20 . A compound of Formula V or VI, 
     
       
         
         
             
             
         
       
     
     wherein one or more of R1-R5 is independently chosen from-L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl, and the others of R1-R5, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(—O) 2 (C 1-3 alkyl), —S(—O) 2 NH 2 , —S(—O) 2 N(C 1-3 alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;
 R o  is chosen from alkyl and haloalkyl; 
 R6-R10, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl, heterocyclic, or cycloalkyl ring; 
 R11 is an optionally substituted heterocyclic group; and 
 L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl. 
 
   
   
       21 . A compound of Formula V or VI, 
     
       
         
         
             
             
         
       
     
     wherein R1-R11, independent of one another, are chosen from -L-R12, -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3  alkyl) 2 , -L-S(═O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl;
 R o  is chosen from alkyl and haloalkyl; 
 R12 is a heterocyclic group with one or more substituents independently chosen -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3  alkyl), -L-C(═O)N(C 1-3  alkyl) 2 , -L-S(—O) 2 (C 1-3 alkyl), -L-S(—O) 2 NH 2 , -L-S(—O) 2 N(C 1-3  alkyl) 2 , -L-S(—O) 2 NH(C 1-3  alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl; and 
 the others of R1-R11 are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1 -3  alkyl) 2 , —NH(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(—O)N(C 1-3 alkyl) 2 , —S(—O) 2 (C 1-3 alkyl), —S(—O) 2 NH 2 , —S(—O) 2 N(C 1-3  alkyl) 2 , —S(—O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3  substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl, heterocyclic, or cycloalkyl ring; and 
 L can be saturated, partially saturated, or unsaturated, and is chosen from —(CH 2 ) n —(CH 2 ) n —, —(CH 2 ) n C(═O)(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) n —, —(CH 2 ) n O(CH 2 ) n —, and —(CH 2 ) n S(CH 2 ) n —, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein each carbon can be optionally substituted with one or more C 1-3  alkyl or C 3-6  cycloalkyl. 
 
   
   
       22 . The use of a compound according to  claim 1 , for the manufacture of a medicament useful for the treatment of Alzheimer&#39;s disease. 
   
   
       23 . An orally available unit dosage form having a compound according to  claim 1 . 
   
   
       24 . The unit dosage form of  claim 23  having from 1 mg to 2000 mg of said compound. 
   
   
       25 . The unit dosage form of  claim 23  having from 1 mg to 1000 mg of said compound. 
   
   
       26 . The unit dosage form of  claim 23  having from 1 mg to 800 mg of said compound.
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Compounds for alzheimber&#39;s disease

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Compounds for alzheimber's disease
