Substituted Hydroxyethylamines

Abstract

Disclosed are compounds of the formula and the pharmaceutically acceptable salts thereof wherein the variables G, L, A, W, E, R2, R2, R4, R5, R N , and R C are defined herein. These compounds interact with and inhibit the activity of the enzyme beta-secretase. These compounds are therefore useful in treating Alzheimer's disease and other similar diseases. Pharmaceutical compositions and methods of treatment of these diseases are also disclosed.

1 . A compound of the formula:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein 
 E is a bond or C 1 -C 3  alkylene;  
 R J  is H or benzyloxycarbonyl;  
 R K  is H or C 1 -C 4  alkoxycarbonyl;  
 K is —(CR 4 R 5 ) n —; wherein R 4  and R 5  are independently hydrogen, halogen, C 1 -C 6  alkoxy or C 1 -C 4  alkyl optionally substituted with halogen, —CN, —CF 3 , or —OH;  
 n is 0, 1 or 2;  
 A is: 
 (I) aryl or cycloalkyl where each aryl or cycloalkyl is optionally substituted with one, two or three independently selected R 100  groups, where R 100  is 
 (A) —NO 2 ,  
 (B) —C≡N,  
 (C) —N(R)CO(R′)R, where R and R′ are independently hydrogen, C 1 -C 6  alkyl, or —(CH 2 ) 0-2 -aryl or —(CH 2 ) 0-2 -cycloalkyl, where each aryl or cycloalkyl is optionally substituted with halogen, hydroxy, C 1 -C 6  alkyl, C 1 -C 6  alkyl, amino, mono(C 1 -C 6 )alkylamino, or di(C 1 -C 6 )alkylamino,  
 (D) —CO 2 —R 25 , where R 25  is selected from the group consisting of: 
 (a) C 1 -C 6  alkyl,  
 (b) —(CH 2 ) 0-2 -cycloalkyl,  
 (c) —(CH 2 ) 0-2 -aryl, where the aryl is optionally substituted with halogen, hydroxy, C 1 -C 6  alkyl, C 1 -C 6  alkyl, amino, mono(C 1 -C 6 )alkylamino, or di(C 1 -C 6 )alkylamino, and  
 (d) hydrogen,  
 
 (E) —NH—CO 2 —R 25 ,  
 (F) —O—(C 2 -C 6  alkyl)-CO 2 H,  
 (G) —NRR′,  
 (H) —SR,  
 (I) —CH 2 OH,  
 (J) —C(O)—(C 1 -C 6 )alkyl,  
 (K) —C(O)NRR′,  
 (L) —SO 2 NRR′ 
 (M) —CO 2 H,  
 (N) C 1 -C 6  alkyl, C 1 -C 6  alkenyl with one or two double bonds, —C 1 -C 6  alkynyl with one or two triple bonds, —CF 3 , —F, —Cl, —Br, —I, C 1 -C 3  alkoxy, —OCF 3 , —NH 2 , —OH, or —CN,  
 (O) halogen, and  
 (P) —(CH 2 ) 0-2 —O—(CH 2 ) 0-2 —OH;  
 
 (II) heteroaryl, provided that, when E is a bond, the heteroaryl group is bonded through one of its carbon atoms to W, and where the heteroaryl is optionally substituted with one or two independently selected R 100  groups;  
 (III) heterocycle, provided that, when E is a bond, the heterocycle group is bonded through one of its carbon atoms to W, where the heterocycle is optionally substituted with one or two independently selected R 200  groups, where R 200  is 
 (1) ═O,  
 (2) C 1 -C 3  alkyl,  
 (3) —CF 3 ,  
 (4) —F, Cl, —Br and —I,  
 (5) C 1 -C 3  alkoxy,  
 (6) —OCF 3 ,  
 (7) —NH 2 ,  
 (8) —OH, or  
 (9) —C≡N;  
 
 
 W is a bond, —S—, —S(O)—, —SO 2 —, —O—, —N(R)— where R is hydrogen or C 1 -C 4  alkyl;  
 L is a bond or absent when G is absent, or L is —C(O)—, —S(O)—, —SO 2 —, —O—, —C(R 110 )(R 112 )O—, —OC(R 110 )(R 112 )—, —N(R 110 )—, —CON(R 110 )—, —N(R 110 )CO—, —C(R 110 )(R′)—, —C(OH)R 110 —, —SO 2 NR 110 —, —N(R 110 )SO 2 —, —N(R 110 )CON(R 112 )—, N(R 110 )CSN(R 112 )—, —OCO 2 —, —NCO 2 —, or —OCON(R 110 )—, where R 110  and R 112  are independently hydrogen, or C 1 -C 4  alkyl, where C 1 -C 4  alkyl is optionally substituted with OH, C 1 -C 4  alkoxy, or one to five F;  
 G is absent or: 
 (I) C 1 -C 10  alkyl, optionally substituted with up to three groups independently selected from 
 (A) —CO 2 H,  
 (B) —CO 2 (C 1 -C 4  alkyl),  
 (C) C 1 -C 6  alkoxy,  
 (D) —OH,  
 (E) —NRR′,  
 (F) —C 1 -C 6  haloalkyl,  
 (G) —(C 1 -C 10  alkyl)-O—(C 1 -C 3  alkyl),  
 (H) —C 1 -C 10  alkenyl with one or two double bonds,  
 (I) —C 1 -C 10  alkynyl with one or two triple bonds,  
 (J) —C 1 -C 10  alkyl chain with one double bond and one triple bond,  
 (K) aryl optionally substituted with R 100 ,  
 (L) heteroaryl optionally substituted with R 100 ,  
 (M) C 1 -C 6  alkyl,  
 
 (II) —(CH 2 ) 0-3 —(C 3 -C 7 ) cycloalkyl where cycloalkyl is optionally substituted with one, two or three substituents selected from the group consisting of: 
 (A) —CO 2 H,  
 (B) —CO 2 —(C 1 -C 4  alkyl),  
 (C) C 1 -C 6  alkoxy,  
 (D) —OH,  
 (E) —NH 2 ,  
 (F) —C 1 -C 6  haloalkyl,  
 (G) —(C 1 -C 10  alkyl)-O—(C 1 -C 3  alkyl),  
 (H) —C 1 -C 10  alkenyl with one or two double bonds,  
 (I) —C 1 -C 10  alkynyl with one or two triple bonds,  
 (J) —C 1 -C 10  alkyl chain with one double bond and one triple bond,  
 (K) aryl optionally substituted with R 100 ,  
 (L) heteroaryl optionally substituted with R 100 ,  
 (m) mono(C 1 -C 6  alkyl)amino, and  
 (n) di(C 1 -C 6  alkyl)amino,  
 (o)C 1 -C 6  alkyl,  
 
 (III) —(CRR) 0-4 -aryl where aryl is optionally substituted with R 100 ,  
 (IV) —(CH 2 ) 0-4 -heteroaryl where the heteroaryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (V) —(CH 2 ) 0-4 -heterocycle, where the heterocycle is optionally substituted with one or two R 200  groups,  
 (VI) —C(R 10 )(R 12 )—CO—NH—R 14  where 
 R 10  and R 12  are the same or different and are selected from the group consisting of:  
 (A) —H,  
 (B) —C 1 -C 6  alkyl,  
 (C) —(C 1 -C 4  alkyl)-aryl, where the aryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (D) —(C 1 -C 4  alkyl)-heteroaryl where the heteroaryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (E) —(C 1 -C 4  alkyl)-heterocycle, where the heterocycle is optionally substituted with one or two R 200  groups,  
 (F) heteroaryl where the heteroaryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (G) heterocycle, where the heterocycle is optionally substituted with one or two R 200  groups,  
 (H) —(CH 2 ) 1-4 —OH,  
 (I) —(CH 2 ) 1-4 —Y—(CH 2 ) 14 -aryl where Y is —O—, —S— or —NR C-5 — where R 16  is hydrogen or C 1 -C 6  alkyl, and where the aryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (J) —(CH 2 ) 1-4 —Y—(CH 2 ) 1-4 -heteroaryl where the heteroaryl is optionally substituted with one, two, or three independently selected R 100  groups, and  
 (K) -aryl, where the aryl is optionally substituted with one, two, or three independently selected R 100  groups, and  
 R 14  is:  
 (A) —H,  
 (B) —C 1 -C 6  alkyl,  
 (C) -aryl, where the aryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (D) -heteroaryl where the heteroaryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (E) -heterocycle, where the heterocycle is optionally substituted with one or two R 200  groups,  
 (F) —(C 1 -C 4  alkyl)-aryl, where the aryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (G) —(C 1 -C 4  alkyl)-heteroaryl where the heteroaryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (H) —(C 1 -C 4  alkyl)-heterocycle, where the heterocycle is optionally substituted with one or two R 200  groups, or  
 (I) —(CH 2 ) 0-2 —O—(CH 2 ) 0-2 —OH; R 4  and R 5  are independently hydrogen, halogen, C 1 -C 6 alkoxy or C 1 -C 4  alkyl;  
 
 R 2  is selected from the group consisting of: 
 (I) hydrogen,  
 (II) C 1 -C 6  alkyl,  
 (III) —(CH 2 ) 0-4 -aryl, where the aryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (IV) —(CH 2 ) 0-4 -heteroaryl where the heteroaryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 
 where R 3  is selected from the group consisting of: 
 (I) —H,  
 (II) C 1 -C 6  alkyl, and  
 (III) —(CH 2 ) 0-4 -aryl, where the aryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 (IV) —(CH 2 ) 0-4 -heteroaryl where the heteroaryl is optionally substituted with one, two, or three independently selected R 100  groups,  
 
 
 R N  is: 
 (I) R N-1 —X N — where X N  is selected from the group consisting of: 
 (A) —CO—,  
 (B) —SO 2 —,  
 (C) —(CR′″R′″) 1-6  wherein 
 R′″ and R′″ at each occurrence are the same or different and are —H or C 1 -C 4  alkyl,  
 
 (D) —CO—(CR″R′″) 1-6 —X N-1  wherein 
 X N-1  is selected from the group consisting of —O—, —S— and —NR″—,  
 
 (E) a single bond, and  
 (F) —CO—(CR″R′″) 1-6    
 
 where R N-1  is selected from the group consisting of: 
 (A) R N-aryl  wherein R N-aryl  at each occurrence is independently phenyl; naphthyl; tetralinyl; indanyl; indenyl; dihydronaphthyl; or 6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl; each of which is optionally substituted with one, two or three of the following substituents which can be the same or different and are: 
 (1) C 1 -C 6  alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  wherein R 1-a  and R 1-b  at each occurrence are independently H or C 1 -C 6  alkyl,  
 (2) —OH,  
 (3) —NO 2 ,  
 (4) —F, —Cl, —Br, —I,  
 (5) —CO 2 H,  
 (6) —C≡N,  
 (7) —(CH 2 ) 0-4 —CO—NR N-2 R N-3  where R N-2  and R N-3  are the same or different and are selected from the group consisting of:  
  (a) —H,  
  (b) —C 1 -C 8  alkyl optionally substituted with one substituent selected from the group consisting of:  
  (i) —OH,  
  (ii) —NH 2 ,  
  (iii) phenyl,  
  (c) —C 1 -C 8  alkyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —Br, or —I,  
  (d) —C 3 -C 8  cycloalkyl,  
  (e) —(C 1 -C 2  alkyl)-(C 3 -C 8  cycloalkyl),  
  (f) —(C 1 -C 6  alkyl)-O—(C 1 -C 3  alkyl)  
  (g) —C 2 -C 6  alkenyl,  
  (h) —C 2 -C 6  alkynyl,  
  (i) —C 1 -C 6  alkyl chain with one double bond and one triple bond,  
  (j) —R 1-aryl , wherein  
  R 1-aryl  at each occurrence is independently phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl, or tetralinyl each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently:  
  (i) C 1 -C 6  alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —NR 1-a R 1-b , —C≡N, —CF 3 , and C 1 -C 3  alkoxy,  
  (ii) C 2 -C 6  alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (iii) C 2 -C 6  alkynyl optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (iv) —F, Cl, —Br and —I,  
  (v) —C 1 -C 6  alkoxy optionally substituted with 1, 2, or 3 —F,  
  (vi) —NR N-2 R N-3 ,  
  (vii) —OH,  
  (viii) —C≡N,  
  (ix) C 3 -C 7  cycloalkyl, optionally substituted with 1, 2, or 3 groups that are selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (x) —CO—(C 1 -C 4  alkyl),  
  (xi) —SO 2 —NR 1-a R 1-b ,  
  (xii) —CO—NR 1-a R 1-b , or  
  (xiii) —SO 2 —(C 1 -C 4  alkyl),  
  (k) —R 1-heteroaryl , wherein  
  R 1-heteroaryl  at each occurrence is independently selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pyridazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, pyridinyl-N-oxide, tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, and benzothiopyranyl S,S-dioxide,  
  where the R 1-heteroaryl  group is optionally substituted with 1, 2, 3, or 4 groups that are independently:  
  (i) C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —NR 1-a R 1-b , —C≡N, —CF 3 , and C 1 -C 3  alkoxy,  
  (ii) C 2 -C 6  alkenyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or —NR 1-a R 1-b ,  
  (iii) C 2 -C 6  alkynyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or —NR 1-a R 1-b ,  
  (iv) —F, —Cl, —Br and —I,  
  (v) —C 1 -C 6  alkoxy optionally substituted with one, two, or three —F,  
  (vi) —(CH 2 ) 0-4 —NR N-2 R N-3 ,  
  (vii) —OH,  
  (viii) —C≡N,  
  (ix) (CH 2 ) 0-4 —C 3 -C 7  cycloalkyl, optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (x) (CH 2 ) 0-4 —CO—(C 1 -C 6  alkyl),  
  (xi) (CH 2 ) 0-4 —SO 2 —NR N-2 R N-3 ,  
  (xii) (CH 2 ) 0-4 —CO—NR N-2 R N-3 ,  
  (xiii) (CH 2 ) 0-4 —SO 2 —(C 1 -C 6  alkyl),  
  (xiv) (CH 2 ) 0-4 —N(R N-2 )—SO 2 —, and  
  (xv) (CH 2 ) 0-4 —N(R N-2 )—C(O)—,  
  (l) —R 1-heterocycle , wherein  
  R 1-heterocycle  at each occurrence is independently selected from the group consisting of morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl S-oxide, tetrahydrothienyl S,S-dioxide, and homothiomorpholinyl S-oxide,  
  where the R 1-heterocycle  group is bonded by any atom of the parent R 1-heterocycle  group substituted by hydrogen such that the new bond to the R 1-heterocycle  group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with 1, 2, 3, or 4 groups that are independently:  
  (a) C 1 -C 6  alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, halogen, —OH, —SH, —NR 1-a R 1-b  —C≡N, —CF 3 , and C 1 -C 3  alkoxy,  
  (b) C 2 -C 6  alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b    
  (c) C 2 -C 6  alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b    
  (d) halogen,  
  (e) C 1 -C 6  alkoxy,  
  (f) —C 1 -C 6  alkoxy optionally substituted with one, two, or three —F,  
  (g) —NR N-2 R N-3 ,  
  (h) —OH,  
  (i) —C≡N,  
  (j) (CH 2 ) 0-4 —(C 3 -C 8  cycloalkyl), optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (k) —(CH 2 ) 0-4 —CO—(C 1 -C 4  alkyl),  
  (l) —(CH 2 ) 0-4 —SO 2 —NR 1-a R 1-b ,  
  (m) —(CH 2 ) 0-4 —CO—NR 1-a R 1-b ,  
  (n) —(CH 2 ) 0-4 —SO 2 —(C 1 -C 6  alkyl), and  
  (o) ═O,  
  (p) —(CH 2 ) 0-4 —N(R N-2 )—SO 2    
  (q) —(CH 2 ) 0-4 —N(R N-2 )—C(O)— 
 (8) —(CH 2 ) 0-4 —CO—(C 1 -C 12  alkyl),  
 (9) —(CH 2 ) 0-4 —CO—(C 2 -C 12  alkenyl),  
 (10) —(CH 2 ) 0-4 —CO—(C 2 -C 12  alkynyl),  
 (11) —(CH 2 ) 0-4 —CO—(C 3 -C 8  cycloalkyl),  
 (12) —(CH 2 ) 0-4 —CO—R 1-aryl ,  
 (13) —(CH 2 ) 0-4 —CO—R 1-heteroaryl ,  
 (14) —(CH 2 ) 0-4 —CO—R 1-heterocycle ,  
 (15) —(CH 2 ) 0-4 —CO—R N-4  wherein R N-4  is selected from the group consisting of phenyl, morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl, thienyl, pyrazolyl, pyridyl N-oxide, oxazolyl, thiazolyl, imidazolyl, and pyrrolidinyl where each group is optionally substituted with one, two, three, or four groups that are independently C 1 -C 6  alkyl,  
 (16) —(CH 2 ) 0-4 —CO—O—R N-5  where R N-5  is selected from the group consisting of:  
  (a) C 1 -C 6  alkyl,  
  (b) —(CH 2 ) 0-2 —(R 1-aryl ),  
  (c) C 2 -C 6  alkenyl,  
  (d) C 2 -C 6  alkynyl,  
  (e) —(CH 2 ) 0-2 —C 3 -C 8  cycloalkyl,  
  (f) —(CH 2 ) 0-2 —(R 1-heteroaryl ), and  
  (g) —(CH 2 ) 0-2 —(R 1-heterocycle ),  
 (17) —(CH 2 ) 0-4 —SO 2 —NR N-2 R N-3 ,  
 (18) —(CH 2 ) 0-4 —SO—(C 1 -C 8  alkyl),  
 (19) —(CH 2 ) 0-4 —SO 2 —(C 1 -C 12  alkyl),  
 (20) —(CH 2 ) 0-4 —SO 2 —(C 3 -C 8  cycloalkyl),  
 (21) —(CH 2 ) 0-4 —N(H or R N-5 )—CO—O—R N-5 ,  
 (22) —(CH 2 ) 0-4 —N(H or R N-5 )—CO—N(R N-5 ) 2 ,  
 (23) —(CH 2 ) 0-4 —N—CS—N(R N-5 ) 2 ,  
 (24) —(CH 2 ) 0-4 —N(H or R N-5 )—CO—R N-2 ,  
 (25) —(CH 2 ) 0-4 —NR N-2 R N-3 ,  
 (26) —(CH 2 ) 0-4 —R N-4 ,  
 (27) —(CH 2 ) 0-4 —CO—(C 1 -C 6  alkyl),  
 (28) —(CH 2 ) 0-4 —O—P(O)—(OR 100 ) 2  wherein  
  R 100  at each occurrence is independently —H or C 1 -C 4  alkyl,  
 (29) —(CH 2 ) 0-4 —O—CO—N(R N-5 ) 2 ,  
 (30) —(CH 2 ) 0-4 —O—CS—N(R N-5 ) 2 ,  
 (31) —(CH 2 ) 0-4 —O—(R N-5 ),  
 (32) —(CH 2 ) 0-4 —O—(R N-5 )—COOH,  
 (33) —(CH 2 ) 0-4 —S—(R N-5 ),  
 (34) —(CH 2 ) 0-4 —O—(C 1 -C 6  alkyl optionally substituted with one, two, three, four, or five of —F),  
 (35) C 3 -C 8  cycloalkyl,  
 (36) C 2 -C 6  alkenyl optionally substituted with C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or NR 1-a R 1-b ,  
 (37) C 2 -C 6  alkynyl optionally substituted with C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or NR 1-a R 1-b ,  
 (38) —(CH 2 ) 0-4 —N(H or R N-5 )—SO 2 —R N-2 ,  
 (39) —(CH 2 ) 1-4 —(C 3 -C 8  cycloalkyl),  
 
 (B) —R N-heteroaryl  where R N-heteroaryl  is selected from the group consisting of: pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pyridazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzisothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, henoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyridinyl-N-oxide, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide, imidazopyrazolyl, quinazolinonyl, pyrazopyridyl, benzooxadiazolyl, dihydropyrimidinonyl, and dihydrobenzfuranonyl,  
 where the R N-heteroaryl  group is bonded by any atom of the parent R N-heteroaryl  group substituted by hydrogen such that the new bond to the R N-heteroaryl  group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four of: 
 (1) C 1 -C 6  alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
 (2) —OH,  
 (3) —NO 2 ,  
 (4) —F, —Cl, —Br, —I,  
 (5) —CO 2 H,  
 (6) —C≡N,  
 (7) —(CH 2 ) 0-4 —CO—NR N-2 R N-3 ,  
 (8) —(CH 2 ) 0-4 —CO—(C 1 -C 12  alkyl),  
 (9) —(CH 2 ) 0-4 —CO—(C 2 -C 12  alkenyl),  
 (10) —(CH 2 ) 0-4 —CO—(C 2 -C 12  alkynyl),  
 (11) —(CH 2 ) 0-4 —CO—(C 3 -C 8  cycloalkyl),  
 (12) —(CH 2 ) 0-4 —CO—R 1-aryl ,  
 (13) —(CH 2 ) 0-4 —CO—R 1-heteroaryl ,  
 (14) —(CH 2 ) 0-4 —CO—R 1-heterocycle ,  
 (15) —(CH 2 ) 0-4 —CO—R N-4    
 (16) —(CH 2 ) 0-4 —CO—O—R N-5    
 (17) —(CH 2 ) 0-4 —SO 2 —NR N-2 R N-3 ,  
 (18) —(CH 2 ) 0-4 —SO—(C 1 -C 8  alkyl),  
 (19) —(CH 2 ) 0-4 —SO 2  (C 1 -C 12  alkyl),  
 (20) —(CH 2 ) 0-4 —SO 2 —(C 3 -C 8  cycloalkyl),  
 (21) —(CH 2 ) 0-4 —N(H or R N-5 )—CO—O—R N-5,    
 (22) —(CH 2 ) 0-4 —N(H or R N-5 )—CO—N(R N-5 ) 2 ,  
 (23) —(CH 2 ) 0-4 —N—CS—N(R N-5 ) 2 ,  
 (24) —(CH 2 ) 0-4 —N(—H or R N-5 )—CO—R N-2 ,  
 (25) —(CH 2 ) 0-4 —NR N-2 R N-3 ,  
 (26) —(CH 2 ) 0-4 —R N-4 ,  
 (27) —(CH 2 ) 0-4 —O—CO—(C 1 -C 6  alkyl),  
 (28) —(CH 2 ) 0-4 —O—P(O)—(OR 100 ) 2 ,  
 (29) —(CH 2 ) 0-4 —O—CO—N(R N-5 ) 2 ,  
 (30) —(CH 2 ) 0-4 —O—CS—N(R N-5 ) 2 ,  
 (31) —(CH 2 ) 0-4 —O—(R N-5 ),  
 (32) —(CH 2 ) 0-4 —O—(R N-5 )—COOH,  
 (33) —(CH 2 ) 0-4 —S—(R N-5 ),  
 (34) —(CH 2 ) 0-4 —O—(C 1 -C 6  alkyl optionally substituted with one, two, three, four, or five of —F),  
 (35) C 3 -C 8  cycloalkyl,  
 (36) C 2 -C 6  alkenyl optionally substituted with C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or NR 1-a R 1-b ,  
 (37) C 2 -C 6  alkynyl optionally substituted with C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or NR 1-a R 1-b ,  
 (38) —(CH 2 ) 0-4 —N(—H or R N-5 )—SO 2 —R N-2 ,  
 (39) —(CH 2 ) 1-4 —C 3 -C 8  cycloalkyl,  
 
 (C) R N-aryl -W—R N-aryl ,  
 (D) R N-aryl -W—R N-heteroaryl ,  
 (E) R N-aryl -W—R 1-heterocycle ,  
 (F) R N-heteroaryl -W—R N-aryl ,  
 (G) R N-heteroaryl -W—R N-heteroaryl ,  
 (H) R N-heteroaryl -W—R N-1-heterocycle ,  
 (I) R N-heterocycle -W—R N-aryl ,  
 (J) R N-heterocycle -W—R N-heteroaryl ,  
 (K) R N-heterocycle -W—R N-1-heterocycle , 
 where W is  
  (1) —(CH 2 ) 1-4 —,  
  (2) —O—,  
  (3) —S(O) 0-2 —,  
  (4) —N(R N-5 ) —,  
  (5) —CO—; or  
  (6) a bond;  
 
 
 (II) —CO—(C 1 -C 10  alkyl) wherein the alkyl is optionally substituted with one two or three substituents independently selected from the group consisting of: 
 (A) —OH,  
 (B) —C 1 -C 6  alkoxy,  
 (C) —C 1 -C 6  thioalkoxy,  
 (D) —CO—O—R N-8  where 
 R N-8  at each occurrence is independently —H, C 1 -C 6  alkyl or -phenyl,  
 
 (E) —CO—NR N-2 R N-3 ,  
 (F) —CO—R N-4 ,  
 (G)-SO 2 —(C 1 -C 8  alkyl),  
 (H) —SO 2 —NR N-2 R N-3 ,  
 (I) —NH—CO—(C 1 -C 6  alkyl),  
 (J) —NH—CO—O—R N-8 ,  
 (K) —NR N-2 R N-3 ,  
 (L) —R N-4 ,  
 (M) —O—CO—(C 1 -C 6  alkyl),  
 (N) —O—CO—NR N-8 R N-8 ,  
 (O) —O—(C 1 -C 5  alkyl)-COOH,  
 (P) —O—(C 1 -C 6  alkyl optionally substituted with one, two, or three of —F, —CI, —Br, —I),  
 (Q) —NH—SO 2 —(C 1 -C 6  alkyl),  
 (R) halogen,  
 (S) —N(H or R N-5 )—SO 2 —R N-2 ,  
 (T) —N(H or R N-5 )—CO—(R N-2 ), and  
 (U) —SO 2 —R N-2 ,  
 
 (III) —CO—(C 1 -C 6  alkyl)-O—(C 1 -C 6  alkyl) wherein each alkyl is unsubstituted or independently substituted with one, two, or three substituents selected from the group consisting of 
 (A) —OH,  
 (B) —C 1 -C 6  alkoxy,  
 (C) —C 1 -C 6  thioalkoxy,  
 (D) —CO—O—R N-8 ,  
 (E) —CO—NR N-2 R N-3 ,  
 (F) —CO—R N-4 ,  
 (G)-SO 2 —(C 1 -C 8  alkyl),  
 (H) —SO 2 —NR N-2 R N-3 ,  
 (I) —NH—CO—(C 1 -C 6  alkyl),  
 (J) —NH—CO—O—R N-8 ,  
 (K) —NR N-2 R N-3 ,  
 (L) —R N-4 ,  
 (M) —O—CO—(C 1 -C 6  alkyl),  
 (N) —O—CO—NR N-8 R N-8 ,  
 (O) —O—(C 1 -C 5  alkyl)-CO 2 H,  
 (P) —O—(C 1 -C 6  alkyl optionally substituted with one, two, or three groups that are independently —F, —CI, —Br, or —I),  
 (Q) —NH—SO 2 —(C 1 -C 6  alkyl),  
 (R) halogen,  
 (S) —N(H or R N-5 )—SO 2 —R N-2 ,  
 (T) —N(H or R N-5 )—CO—(R N-2 ), and  
 (U) —SO 2 —R N-2 ,  
 
 (IV) —CO—(C 1 -C 6  alkyl)-S—(C 1 -C 6  alkyl) wherein each alkyl is unsubstituted or substituted with one, two, or three of substituents independently selected from the group consisting of: 
 (A) —OH,  
 (B) —C 1 -C 6  alkoxy,  
 (C) —C 1 -C 6  thioalkoxy,  
 (D) —CO—O—R N-8 ,  
 (E) —CO—NR N-2 R N-3 ,  
 (F) —CO—R N-4 ,  
 (G) —SO 2 —(C 1 -C 8  alkyl),  
 (H) —SO 2 —NR N-2 R N-3 ,  
 (I) —NH—CO—(C 1 -C 6  alkyl),  
 (J) —NH—CO—O—R N-8 ,  
 (K) —NR N-2 R N-3 ,  
 (L) —R N-4 ,  
 (M) —O—CO—(C 1 -C 6  alkyl),  
 (N) —O—CO—NR N-8 R N-8 ,  
 (O) —O—(C 1 -C 5  alkyl)-COOH,  
 (P) —O—(C 1 -C 6  alkyl optionally substituted with one, two, or three groups that are independently —F, —Cl, —Br, or —I),  
 (Q) —NH—SO 2 —(C 1 -C 6  alkyl),  
 (R) halogen,  
 (S) —N(H or R N-5 )—SO 2 —R N-2 ,  
 (T) —N(H or R N-5 )—CO—(R N-2 ), and  
 (U) —SO 2 —R N-2 ,  
 
 (V) —CO—CH(—(CH 2 ) 0-2 —O—R N-10 )—(CH 2 ) 0-2 —R N-aryl /R N-heteroaryl ) wherein 
 R N-10  is selected from the group consisting of:  
 (A) —H,  
 (B) C 1 -C 6  alkyl,  
 (C) C 3 -C 8  cycloalkyl,  
 (D) C 2 -C 6  alkenyl with one double bond,  
 (E) C 2 -C 6  alkynyl with one triple bond,  
 (F) R 1-aryl ,  
 (G) R N-heteroaryl ,  
 (H) R N-heterocycle ,  
 
 (VI) —CO—(C 3 -C 8  cycloalkyl) where the cycloalkyl group is optionally substituted with one or two substituents independently selected from the group consisting of: 
 (A) —(CH 2 ) 0-4 —OH,  
 (B) —(CH 2 ) 0-4 —C 1 -C 6  alkoxy,  
 (C) —(CH 2 ) 0-4 —C 1 -C 6  thioalkoxy,  
 (D) —(CH 2 ) 0-4 —CO—O—R N-8 ,  
 (E) —(CH 2 ) 0-4 —CO—NR N-2 R N-3 ,  
 (F) —(CH 2 ) 0-4 —CO—R N-4 ,  
 (G) —(CH 2 ) 0-4 —SO 2 —(C 1 -C 8  alkyl),  
 (H) —(CH 2 ) 0-4 —SO 2 —NR N-2 R N-3 ,  
 (I) —(CH 2 ) 0-4 —NH—CO—(C 1 -C 6  alkyl),  
 (J) —NH—CO—O—R N-8 ,  
 (K) —(CH 2 ) 0-4 —NR N-2 R N-3 ,  
 (L) —(CH 2 ) 0-4 —R N-4 ,  
 (M) —O—CO—(C 1 -C 6  alkyl),  
 (N) —O—CO—NR N-8 R N-8 ,  
 (O) —O—(C 1 -C 6  alkyl)-CO 2 H,  
 (P) —O—(C 1 -C 6  alkyl optionally substituted with one, two, or three groups that are independently selected from —F, —Cl, —Br, and —I),  
 (Q) —NH—SO 2 —(C 1 -C 6  alkyl),  
 (R) halogen,  
 (S) —N(H or R N-5 )—SO 2 —R N-2 , and  
 (T) —N(H or R N-5 )—CO—(R N-2 ), and  
 (U) —SO 2 —R N-2 ; and  
 
 
 R C  is selected from the group consisting of: 
 (I) —C 1 -C 10  alkyl optionally substituted with one, two or three groups independently selected from the group consisting of C 1 -C 3  alkyl, halogen, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, —NR 1-a R 1-b , —OC═O NR 1-a R 1-b , —S(═O) 0-2 R 1-a , —NR 1-a C═O NR 1-a R 1-b , —C═O NR 1-a R 1-b , and —S(═O) 2  NR 1-a R 1-b  wherein  
 R 1-a  and R 1-b  at each occurrence are independently H or C 1 -C 6  alkyl,  
 (II) —(CH 2 ) 0-3 —(C 3 -C 8 ) cycloalkyl where cycloalkyl can be optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, halogen, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, —CO 2 H, —CO 2 —(C 1 -C 4  alkyl), and —NR 1-a R 1-b    
 (III) —(CR C-x R C-y ) 0-4 —R C-aryl  where R C-x  and R C-y  are independently selected from the group consisting of 
 —H,  
 C 1 -C 4  alkyl optionally substituted with 1 or 2 —OH,  
 C 1 -C 4  alkoxy optionally substituted with 1, 2, or 3 halogen,  
 —(CH 2 ) 0-4 —C 3 -C 8  cycloalkyl,  
 C 2 -C 6  alkenyl containing one or two double bonds,  
 C 2 -C 6  alkynyl containing one or two triple bonds, and phenyl,  
 
 or 
 R C-x  and R C-y  are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, where one carbon atom is optionally replaced by a group selected from —O—, —S—, —SO 2 —, —NR N-2 — and R C-aryl , wherein 
 R C-aryl  at each occurrence is independently phenyl; naphthyl; tetralinyl; indanyl; dihydronaphthyl; or 6,7,8,9-tetrahydro-5H-benzo[a]cycloheptenyl, each of which is optionally substituted with 1, 2, or 3 groups that are independently:  
  (1) C 1 -C 6  alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C 1 -C 3  alkyl, halogen, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (2) —OH,  
  (3) —NO 2 ,  
  (4) halogen,  
  (5) —CO 2 H,  
  (6) —C≡N,  
  (7) —(CH 2 ) 0-4 —CO—NR N-2 R N-3  where  
  R N-2  and R N-3  are independently selected from the group consisting of:  
  (a) —H,  
  (b) —C 1 -C 6  alkyl optionally substituted with one substituent selected from the group consisting of:  
  (i) —OH, and  
  (ii) —NH 2 ,  
  (c) —C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —Br, —I, or OH,  
  (d) —C 3 -C 7  cycloalkyl,  
  (e) —(C 1 -C 2  alkyl)-(C 3 -C 7  cycloalkyl),  
  (f) —(C 1 -C 6  alkyl)-O—(C 1 -C 3  alkyl),  
  (g) —C 2 -C 6  alkenyl  
  (h) —C 2 -C 6  alkynyl  
  (i) —C 1 -C 6  alkyl chain with one double bond and one triple bond,  
  (j) —R 1-aryl  wherein R 1-aryl  at each occurrence is independently phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl, or tetralinyl each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently:  
  (i) C 1 -C 6  alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —NR 1-a R 1-b , —C≡N, —CF 3 , and C 1 -C 3  alkoxy,  
  (ii) C 2 -C 6  alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (iii) C 2 -C 6  alkynyl optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (iv) —F, Cl, —Br and —I,  
  (v) —C 1 -C 6  alkoxy optionally substituted with 1, 2, or 3-F,  
  (vi) —NR N-2 R N-3 ,  
  (vii) —OH,  
  (viii) —C≡N,  
  (ix) C 3 -C 7  cycloalkyl, optionally substituted with 1, 2, or 3 groups that are selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (x) —CO—(C 1 -C 4  alkyl),  
  (xi) —SO 2 —NR 1-a R 1-b ,  
  (xii) —CO—NR 1-a R 1-b , or  
  (xiii) —SO 2 —(C 1 -C 4  alkyl),  
  (k) —R 1-heteroaryl  wherein R 1-heteroaryl  at each occurrence is independently selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pyridazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, pyridinyl-N-oxide, tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, and benzothiopyranyl S,S-dioxide,  
  where the R 1-heteroaryl  group is optionally substituted with 1, 2, 3, or 4 groups that are independently:  
  (i) C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —NR 1-a R 1-b , —C≡N, —CF 3 , and C 1 -C 3  alkoxy,  
  (ii) C 2 -C 6  alkenyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (iii) C 2 -C 6  alkynyl optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (iv) —F, —Cl, —Br and —I,  
  (v) —C 1 -C 6  alkoxy optionally substituted with one, two, or three —F,  
  (vi) —(CH 2 ) 0-4 —NR N-2 R N-3 ,  
  (vii) —OH,  
  (viii) —C≡N,  
  (ix) (CH 2 ) 0-4 —C 3 -C 7  cycloalkyl, optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (x) (CH 2 ) 0-4 —CO—(C 1 -C 6  alkyl),  
  (xi) (CH 2 ) 0-4 —SO 2 —NR N-2 R N-3 ,  
  (xii) (CH 2 ) 0-4 —CO—NR N-2 R N-3 ,  
  (xiii) (CH 2 ) 0-4 —SO 2 —(C 1 -C 6  alkyl),  
  (xiv) (CH 2 ) 4 —N(R N-2 )—SO 2 —, and  
  (xv) (CH 2 ) 0-4 —N(R N-2 )—C(O)—,  
  (8) —(CH 2 ) 0-4 —CO—(C 1 -C 12  alkyl),  
  (9) —(CH 2 ) 0-4 —CO—(C 2 -C 12  alkenyl),  
  (10) —(CH 2 ) 0-4 —CO—(C 2 -C 12  alkynyl),  
  (11) —(CH 2 ) 0-4 —CO—(CH 2 ) 0-4  (C 3 -C 7  cycloalkyl),  
  (12) —(CH 2 ) 0-4 —CO—R 1-aryl ,  
  (13) —(CH 2 ) 0-4 —CO—R 1-heteroaryl ,  
  (14) —(CH 2 ) 0-4 —CO—R 1-heterocycle  wherein  
  R 1-heterocycle  at each occurrence is independently selected from the group consisting of morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl S-oxide, tetrahydrothienyl S,S-dioxide, and homothiomorpholinyl S-oxide,  
  where the R 1-heterocycle  group is bonded by any atom of the parent R 1-heterocycle  group substituted by hydrogen such that the new bond to the R 1-heterocycle  group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with 1, 2, 3, or 4 groups that are independently:  
  (a) C 1 -C 6  alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, halogen, —OH, —SH, —NR 1-a R 1-b  —C≡N, —CF 3 , and C 1 -C 3  alkoxy,  
  (b) C 2 -C 6  alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b    
  (c) C 2 -C 6  alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b    
  (d) halogen,  
  (e) C 1 -C 6  alkoxy,  
  (f) —C 1 -C 6  alkoxy optionally substituted with one, two, or three —F,  
  (g) —NR N-2 R N-3 ,  
  (h) —OH,  
  (i) —C≡N,  
  (j) (CH 2 ) 0-4 —(C 3 -C 7  cycloalkyl), optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
  (k) —(CH 2 ) 0-4 —CO—(C 1 -C 4  alkyl),  
  (l) —(CH 2 ) 0-4 —SO 2 —NR 1-a R 1-b ,  
  (m) —(CH 2 ) 0-4 —CO—NR 1-a R 1-b ,  
  (n) —(CH 2 ) 0-4 —SO 2 —(C 1 -C 6  alkyl), and  
  (o) ═O,  
  (p) —(CH 2 ) 0-4 —N(R N-2 )—SO 2 — 
  (q) —(CH 2 ) 0-4 —N(R N-2 )—C(O)— 
  (15) —(CH 2 ) 0-4 —CO—R N-4  wherein  
  R N-4  at each occurrence is independently selected from the group consisting of morpholinyl, thiomorpholinyl, pyrrolidinonyl, pyrrolyl, pyrazolyl, thienyl, pyridyl N-oxide, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6  alkyl,  
  (16) —(CH 2 ) 0-4 —CO 2 —R N-5  where  
  R N-5  at each occurrence is independently selected from the group consisting of:  
  (a) C 1 -C 6  alkyl,  
  (b) —(CH 2 ) 0-2 —(R 1-aryl ),  
  (c) C 2 -C 6  alkenyl,  
  (d) C 2 -C 6  alkynyl,  
  (e) C 3 -C 7  cycloalkyl, and  
  (f) —(CH 2 ) 0-4 —(R 1-heteroaryl ),  
  (17) —(CH 2 ) 0-4 —SO 2 —NR N-2 R N-3    
  (18) —(CH 2 ) 0-4 —SO—(C 1 -C 8  alkyl),  
  (19) —(CH 2 ) 0-4 —SO 2 —(C 1 -C 12  alkyl),  
  (20) —(CH 2 ) 0-4 —SO 2 —(C 3 -C 7  cycloalkyl),  
  (21) —(CH 2 ) 0-4 —N(H or R N-5 )—CO 2 —R N-5 ,  
  (22) —(CH 2 ) 0-4 —N(H or R N-5 )—CO—N(R N-5 ) 2 ,  
  (23) —(CH 2 ) 0-4 —N—CS—N(R N-5 ) 2 ,  
  (24) —(CH 2 ) 0-4 —N(—H or R N-5 )—CO—R N-2 ,  
  (25) —(CH 2 ) 0-4 —NR N-2 R N-3 ,  
  (26) —(CH 2 ) 0-4 —R N-4 ,  
  (27) —(CH 2 ) 0-4 —O—CO—(C 1 -C 6  alkyl),  
  (28) —(CH 2 ) 0-4 —O—P(O)—(OR 100 ) 2  where R 100  is independently H or C 1 -C 4  alkyl,  
  (29) —(CH 2 ) 0-4 —O—CO—N(R N-5 ) 2 ,  
  (30) —(CH 2 ) 0-4 —O—CS—N(R N-5 ) 2 ,  
  (31) —(CH 2 ) 0-4 —O—(R N-5 ),  
  (32) —(CH 2 ) 0-4 —O—(R N-5 )—COOH,  
  (33) —(CH 2 ) 0-4 —S—(R N-5 ),  
  (34) —(CH 2 ) 0-4 —O—(C 1 -C 6  alkyl) wherein the alkyl group is optionally substituted with one, two, three, four, or five substituents independently selected from the group consisting of F, Cl, Br, and I,  
  (35) —(CH 2 ) 0-4 —(C 3 -C 8  cycloalkyl),  
  (36) C 2 -C 6  alkenyl optionally substituted with C 1 -C 3  alkyl, halogen, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or NR 1-a R 1-b ,  
  (37) C 2 -C 6  alkynyl optionally substituted with C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or —NR 1-a R 1-b , and  
  (38) —(CH 2 ) 0-4 —N(—H or R N-5 )—SO 2 —R N-2 ;  
 
 
 (IV) —(CR C-x R C-y ) 0-4 —R C-heteroaryl  wherein 
 R C-heteroaryl  at each occurrence is independently selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pyridazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzoisothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, henoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, imidazopyrazolyl, quinazolinonyl, pyrazopyridyl, benzooxadiazolyl, dihydropyrimidinonyl, dihydrobenzofuranonyl, pyridinyl-N-oxide, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, and benzothiopyranyl S,S-dioxide,  
 
 where the R C-heteroaryl  group is bonded by any atom of the parent R C-heteroaryl  group substituted by hydrogen such that the new bond to the R C-heteroaryl  group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted 1, 2, 3, or 4 groups that are independently: 
 (1) C 1 -C 6  alkyl, optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, and —NR 1-a R 1-b ,  
 (2) —OH,  
 (3) —NO 2 ,  
 (4) —F, —Cl, —Br, —I,  
 (5) —CO—OH,  
 (6) —C≡N,  
 (7) —(CH 2 ) 0-4 —CO—NR N-2 R N-3 ,  
 (8) —(CH 2 ) 0-4 —CO—(C 1 -C 12  alkyl),  
 (9) —(CH 2 ) 0-4 —CO—(C 2 -C 12  alkenyl with one, two or three double bonds),  
 (10) —(CH 2 ) 0-4 —CO—(C 2 -C 12  alkynyl with one, two or three triple bonds),  
 (11) —(CH 2 ) 0-4 —CO—(C 3 -C 7  cycloalkyl),  
 (12) —(CH 2 ) 0-4 —CO—R 1-aryl  where R 1-aryl  is as defined above,  
 (13) —(CH 2 ) 0-4 —CO—R 1-heteroaryl ,  
 (14) —(CH 2 ) 0-4 —CO—R 1-heterocycle ,  
 (15) —(CH 2 ) 0-4 —CO—R N-4 ,  
 (16) —(CH 2 ) 0-4 —CO—O—R N-5 ,  
 (17) —(CH 2 ) 0-4 —SO 2 —NR N-2 R N-3 ,  
 (18) —(CH 2 ) 0-4 —SO—(C 1 -C 8  alkyl),  
 (19) —(CH 2 ) 0-4 —SO 2  (C 1 -C 12  alkyl),  
 (20) —(CH 2 ) 0-4 —SO 2 —(C 3 -C 7  cycloalkyl),  
 (21) —(CH 2 ) 0-4 —N(H or R N-5 )—CO—O—R N-5 ,  
 (22) —(CH 2 ) 0-4 —N(H or R N-5 )—CO—N(R N-5 ) 2 ,  
 (23) —(CH 2 ) 0-4 —N—CS—N(R N-5 ) 2 ,  
 (24) —(CH 2 ) 0-4 —N(—H or R N-5 )—CO—R N-2 ,  
 (25) —(CH 2 ) 0-4 —NR N-2 R N-3 ,  
 (26) —(CH 2 ) 0-4 —R N-4 ,  
 (27) —(CH 2 ) 0-4 —O—CO—(C 1 -C 6  alkyl),  
 (28) —(CH 2 ) O 4 —O—P(O)—(OR 100 ) 2  where R 100  is —H or C 1 -C 4  alkyl,  
 (29) —(CH 2 ) 0-4 —O—CO—N(R N-5 ) 2 ,  
 (30) —(CH 2 ) 0-4 —O—CS—N(R N-5 ) 2 ,  
 (31) —(CH 2 ) 0-4 —O—(R N-5 ),  
 (32) —(CH 2 ) 0-4 —O—(R N-5 )—COOH,  
 (33) —(CH 2 ) 0-4 —S—(R N-5 ),  
 (34) —(CH 2 ) 0-4 —O— (C 1 -C 6  alkyl optionally substituted with one, two, three, four, or five of —F),  
 (35) C 3 -C 7  cycloalkyl,  
 (36) C 2 -C 6  alkenyl optionally substituted with C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or NR 1-a R 1-b ,  
 (37) C 2 -C 6  alkynyl optionally substituted with C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3  alkoxy, or NR 1-a R 1-b ,  
 (38) —(CH 2 ) 0-4 —N(—H or R N-5 )—SO 2 —R N-2 ,  
 (39) —(CH 2 ) 0-4 —(C 3 -C 7  cycloalkyl),  
 
 (V) —(CR C-x R C-y ) 0-4 —R C-aryl -R 101 —R C-aryl ,  
 (VI) —(CR C-x R C-y ) 0-4 —R C-aryl -R 101 —R C-heteroaryl ,  
 (VII) —(CR C-x R C-y ) 0-4 —R C-heteroaryl -R 101 —R C-aryl ,  
 (VIII) —(CR C-x R C-y ) 0-4 —R C-heteroaryl -R 101 —R C-heteroaryl ,  
 (X) —(CR C-x R C-y ) 0-4 —R C-heteroaryl -R 101 —R 1-heterocycle ,  
 (XI) —(CR C-x R C-y ) 0-4 —R 1-heterocycle -R 10l —R C-aryl ,  
 (XII) —(CR C-x R C-y ) 0-4 —R 1-heterocycle -R 101 —R C-heteroaryl ,  
 (XIII) —(CR C-x R C-y ) 0-4 —R 1-heterocycle -R 101 —R 1-heterocycle , wherein 
 R 101  is a bond, (CH 2 ) 0-4 , —O—, —NH—, or —N(C 1 -C 6  alkyl)  
 
 (XIV) —(CR C-x R C-y ) 0-4 —R 1-heterocycle ,  
 (XV) —[C(R C-1 )(R C-2 )] 1-3 —CO—N(R C-3 ) 2  where R C-1  and R C-2  are the same or different and are selected from the group consisting of: 
 (A) —H,  
 (B) —C 1 -C 6  alkyl, optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and —NR 1-a R 1-b ,  
 (C) C 2 -C 6  alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and —NR 1-a R 1-b ,  
 (D) C 2 -C 6  alkynyl optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and —NR 1-a R 1-b ,  
 (E) —(CH 2 ) 1-2 —S(O) 0-2 —(C 1 -C 6  alkyl),  
 (F) —(CH 2 ) 0-4 —C 3 -C 7  cycloalkyl, optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and —NR 1-a R 1-b ,  
 (G) —(C 1 -C 4  alkyl)-R 1-aryl ,  
 (H) —(C 1 -C 4  alkyl)-R C-heteroaryl ,  
 (I) —(C 1 -C 4  alkyl)-R 1-heterocycle ,  
 (J) —R C-heteroaryl ,  
 (K) —R 1-heterocycle ,  
 (M) —(CH 2 ) 1-4 —R C-4 —(CH 2 ) 0-4 —R 1-aryl  where R C-4  is —O—, —S— or —NR(C 1 -C 6  alkyl)-,  
 (N) —(CH 2 ) 1-4 —R C-4 —(CH 2 ) 0-4 —R C-heteroaryl ,  
 (O) —R 1-aryl ,  
 
 
 and where 
 R C-3  at each occurrence is independently: 
 (A) —H,  
 (B) —C 1 -C 6  alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and —NR 1-a R 1-b ,  
 (C) C 2 -C 6  alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, halogen, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and —NR 1-a R 1-b ,  
 (D) C 2 -C 6  alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and —NR 1-a R 1-b ,  
 (E) —(CH 2 ) 0-4 —C 3 -C 7  cycloalkyl, optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and NR 1-a R 1-b ,  
 (F) —R 1-aryl ,  
 (G) —R C-heteroaryl ,  
 (H)—R 1-heterocycle ,  
 (I) —(C 1 -C 4  alkyl)-R 1-aryl ,  
 (J) —(C 1 -C 4  alkyl)-R C-heteroaryl ,  
 (K) —(C 1 -C 4  alkyl)-R 1-heterocycle ,  
 
 (XVI) —CH(R C-aryl ) 2 ,  
 (XVII) —CH(R C-heteroaryl ) 2 ,  
 (XVIII) —CH(R C-aryl )(R C-heteroaryl ),  
 (XIX) -cyclopentyl, -cyclohexyl, or -cycloheptyl ring fused to R C-aryl  or R C-heteroaryl  or R 1-heterocycle  where R C-aryl  or R C-heteroaryl  or R 1-heterocycle  are as defined above where one carbon of cyclopentyl, cyclohexyl, or -cycloheptyl is optionally replaced with NH, NR N-5 , O, S(═O) 0-2 , and where cyclopentyl, cyclohexyl, or -cycloheptyl can be optionally substituted with one or two —C 1 -C 3  alkyl, —F, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, ═O, or —NR 1-a R 1-b ,  
 (XX) C 2 -C 10  alkenyl optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and —NR 1-a R 1-b ,  
 (XXI) C 2 -C 10  alkynyl optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3  alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, —O-phenyl, and —NR 1-a R 1-b ,  
 (XXI) —(CH 2 ) 0-1 —CHR C-6 —(CH 2 ) 0-1 —R C-aryl  wherein 
 R C-6  is —(CH 2 ) 0-6 —OH,  
 
 (XXII) —(CH 2 ) 0-1 —CHR C-6 —(CH 2 ) 0-1 —R C-heteroaryl ,  
 (XXIII) —CH(—R C-aryl  or R C-heteroaryl )-CO—O(C 1 -C 4  alkyl),  
 (XXIV) —CH(—CH 2 OH)—CH(OH)—(C 1 -C 6  alkyl)-NO 2 ,  
 (XXV) —(C 1 -C 6  alkyl)-O—(C 1 -C 6  alkyl)-OH,  
 (XXVII) —CH 2 —NH—CH 2 —CH(—O—CH 2 —CH 3 ) 2 ,  
 (XXVIII) —H, and  
 (XXIX) —(CH 2 ) 0-6 —C(═NR 1-a )(NR 1-a R 1-b )  
 
 
     
     
         2 . A compound or salt according to  claim 1 , which is selected from 
 N-{(1S,2R)-1-[3-(cyclohexylmethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}acetamide hydrochloride;    N′-{(1S,2R)-1-[3-(cyclohexylmethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N,N-dipropylisophthalamide hydrochloride;    N-{(1S,2R)-1-[3-(cyclohexylmethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-{[(trifluoromethyl)sulfonyl]amino}benzamide hydrochloride;    tert-butyl (1S,2R)-1-[3-(cyclohexylmethyl)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate hydrochloride;    tert-butyl (1S,2R)-1-{3-[(tert-butoxycarbonyl)amino]benzyl}-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate hydrochloride;    N-{(1R,2R)-2-hydroxy-3-[(3-iodobenzyl)amino]-1-[(2-naphthylthio)methyl]propyl}-3-methylbenzamide;    N-{(1R,2S)-2-hydroxy-3-[(3-iodobenzyl)amino]-1-[(2-naphthylthio)methyl]propyl}-3-methylbenzamide;    N′-{(1R,2R)-2-hydroxy-3-[(3-iodobenzyl)amino]-1-[(2-naphthylthio)methyl]propyl}-5-methyl-N,N-dipropylisophthalamide; and (2S,3R)-3-amino-1-[(3-iodobenzyl)amino]-4-(2-naphthylthio)butan-2-ol.    
     
     
         3 . A compound according to  claim 1 , wherein the formula is  
       
         
           
           
               
               
           
         
       
     
     
         4 . A compound according to  claim 3 , wherein 
 A is phenyl, or naphthyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 6  alkyl, —O—(C 1 -C 6  alkyl), and —N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl);    E is a bond or C 1 -C 3  alkylene;    K is —(CR 4 R 5 ) n —; wherein R 4  and R 5  are independently hydrogen, halogen, C 1 -C 6  alkoxy or C 1 -C 4  alkyl optionally substituted with halogen, —CN, —CF 3 , or —OH;    n is 0, 1 or 2;    L is a bond, —O—, or —N(R)— where R is hydrogen or C 1 -C 4  alkyl;    G is C 1 -C 10  alkyl, optionally substituted with up to three groups independently selected from 
 (A) halogen,  
 (B) —OH,  
 (C) C 1 -C 6  alkoxy,  
 (D) C 1 -C 6  haloalkyl;  
   R N  is hydrogen, C 1 -C 6  alkanoyl, —C(═O)—(CRR′) 0-6 R 100 , R′ 100 , —SO 2 R′ 110 , or —(CRR′) 1-6 R′ 100 ;    R 2  and R 3  are independently hydrogen, C 1 -C 4  alkyl or benzyl;    R 100  and R′ 100  are independently, phenyl, heteroaryl or -aryl-W-heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from 
 —OR, C 1 -C 6  alkyl, —NO 2 , halogen, —C≡N, —SR, —SO 2 R 145 , —C(═O)R, —OCF 3 , —CF 3 , —O—P(═O) (OR)(OR′)—C(O)NRR, or —(CH 2 ) 0-4 —C 3 -C 7  cycloalkyl; or  
   R 100  is C 1 -C 10  alkyl optionally substituted with 1, 2, or 3 R 115  groups, wherein 
 R 115  at each occurrence is independently halogen, —OH, —CO 2 R, —C 1 -C 6  alkoxy or C 1 -C 6  haloalkoxy;  
   R and R′ at each occurrence are independently hydrogen; C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 groups that are independently F, Cl, Br, or I; or —(C 1 -C 6 )-alkyl;    W is —(CH 2 ) 0-4 —, —O—, —S(O) 0-2 —, —N(R 135 )—, or —C(O)—;    R 135  is C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 7  cycloalkyl, —(CH 2 ) 0-2 -(aryl), —(CH 2 ) 0-2 -(heteroaryl), or —(CH 2 ) 0-2 -(heterocyclyl);    R C  is —CH 2 -aryl, wherein the aryl is optionally substituted with 1, 2, 3, or 4 R 200 , wherein 
 R 200  at each occurrence is independently selected from the group consisting of C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 R 205  groups; OH, alkoxy, —NO 2 ; halogen; —CO 2 H; C≡N; and —(CH 2 ) 0-4 —C 3 -C 7  cycloalkyl;  
   R 205  at each occurrence is independently selected from the group consisting of C 1 -C 6  alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, NH 2 , NH(C 1 -C 6  alkyl), and N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl).    
     
     
         5 . A compound according to  claim 4 , wherein 
 A is phenyl, optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 6  alkyl, —O—(C 1 -C 6  alkyl), and —N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl);    L is a bond, —O— or —N(R)— where R is hydrogen or C 1 -C 4  alkyl;    G is C 1 -C 10  alkyl, optionally substituted with up to three groups independently selected from 
 (A) halogen,  
 (B) —OH,  
 (C) C 1 -C 6  alkoxy,  
 (D) C 1 -C 6  haloalkyl;  
   R N  is hydrogen, C 1 -C 6  alkanoyl, or —C(═O)—R 100 ;    R 100  is heteroaryl which is selected from pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, and imidazolyl, wherein each is optionally substituted with 1, 2, or 3 groups independently selected from —OR, —NO 2 , halogen, —C≡N, —SR, —SO 2 R 145 , —C(═O)R, —OCF 3 , —CF 3 , —O—P(═O)(OR)(OR′), and —N(R)(SO 2 R 145 ), or R 100  is -aryl-W-heteroaryl, wherein aryl is phenyl or naphthyl and heteroaryl is selected from pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, and imidazolyl, wherein each is optionally substituted with 1, 2, or 3 groups independently selected from —OR, —NO 2 , halogen, —C≡N, —SR, —SO 2 R 145 , —C(═O)R, —OCF 3 , —CF 3 , —O—P(═O)(OR)(OR′), and —N(R)(SO 2 R 145 ), or    R 100  is C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 R 115  groups, wherein 
 R 115  at each occurrence is independently halogen, —OH, C 1 -C 6  alkoxy or C 1 -C 6  haloalkoxy;  
   W is —(CH 2 ) 0-4 —, —O—, —S(O) 0-2 —, —N(R 135 )—, or —C(O)—;    R 145  is C 1 -C 6  alkyl or CF 3 ;    R 150  is hydrogen, C 3 -C 7  cycloalkyl, —(C 1 -C 2  alkyl)-(C 3 -C 7  cycloalkyl), C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkyl with one double bond and one triple bond, —R 110 , —R 120 , or 
 C 1 -C 6  alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from —OH, —NH 2 , C 1 -C 3  alkoxy, R 110 , and halogen;  
   R C  is —CH 2 -aryl, wherein the aryl is optionally substituted with 1, 2, 3, or 4 R 200 , wherein 
 R 200  at each occurrence is independently selected from the group consisting of C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 R 205  groups; OH; alkoxy, —NO 2 ; halogen; —CO 2 H; C≡N; 
 R 205  at each occurrence is independently selected from the group consisting of C 1 -C 6  alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, NH 2 , NH(C 1 -C 6  alkyl), and N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl); and  
 
   K is CH 2 .    
     
     
         6 . A compound according to  claim 5 , wherein 
 n is 0, 1, or 2;    A is phenyl, optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 6  alkyl, —O—(C 1 -C 6  alkyl), and —N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl);    L is a bond or —O—;    G is C 1 -C 6  alkyl, optionally substituted with up to three groups independently selected from 
 (A) halogen,  
 (B) —OH,  
 (C) C 1 -C 6  alkoxy,  
 (D) C 1 -C 6  haloalkyl;  
   R N  is hydrogen, C 1 -C 6  alkanoyl, or —C(═O)—R 100 ; 
 R 100  is heteroaryl which is selected from pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, and imidazolyl, wherein each is optionally substituted with 1, 2, or 3 groups independently selected from —OR, —NO 2 , halogen, —C≡N, —SR, —SO 2 R 145 , —C(═O)R, —OCF 3 , —CF 3 , —O—P(═O)(OR)(OR′), and —N(R)(SO 2 R 145 ), or  
 R 100  is -aryl-W-heteroaryl, wherein aryl is phenyl or naphthyl and heteroaryl is selected from pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, and imidazolyl, wherein each is optionally substituted with 1, 2, or 3 groups independently selected from —OR, —NO 2 , halogen, —C≡N, —SR, —SO 2 R 145 , —C(═O)R, —OCF 3 , —CF 3 , —O—P(═O)(OR)(OR′), and —N(R)(SO 2 R 145 ), or  
 R 100  is C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 R 115  groups, wherein  
   R 115  at each occurrence is independently halogen, —OH, C 1 -C 6  alkoxy or C 1 -C 6  haloalkoxy;    R 145  is C 1 -C 6  alkyl or CF 3 ;    R C  is —CH 2 -aryl, wherein the aryl is phenyl or naphthyl, and is optionally substituted with 1, 2, 3, or 4 R 200 , wherein 
 R 200  at each occurrence is independently selected from the group consisting of C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 R 205  groups; OH; alkoxy, —NO 2 ; halogen; —CO 2 H; C≡N;  
 R 205  at each occurrence is independently selected from the group consisting of C 1 -C 6  alkyl, halogen, —OH, —O-phenyl, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, NH 2 , NH(C 1 -C 6  alkyl), and N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl).  
   
     
     
         7 . A compound according to  claim 6 , wherein 
 n is 0, 1, or 2;    A is phenyl, optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 6  alkyl, —O—(C 1 -C 6  alkyl), and —N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl);    L is —O—;    G is C 1 -C 6  alkyl, optionally substituted with up to three groups independently selected from 
 (A) halogen,  
 (B) —OH,  
 (C) C 1 -C 6  alkoxy,  
 (D) C 1 -C 6  haloalkyl;  
   R N  is hydrogen, C 1 -C 4  alkanoyl, or —C(═O)—R 100 ; 
 R 100  is heteroaryl which is selected from pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, and imidazolyl, wherein each is optionally substituted with 1, 2, or 3 groups independently selected from —OR, —NO 2 , halogen, —C≡N, —SR, —SO 2 R 145 , —C(═O)R, —OCF 3 , —CF 3 , and —N(R)(SO 2 R 145 ), or  
 R 100  is -aryl-W-heteroaryl, wherein aryl is phenyl and heteroaryl is selected from thiazolyl, isothiazolyl, oxazolyl, and isoxazolyl, wherein each is optionally substituted with 1, 2, or 3 groups independently selected from —OR, —NO 2 , halogen, —C≡N, —SR, —SO 2 R 145 , —C(═O)R, —OCF 3 , —CF 3 , and —N(R)(SO 2 R 145 ), or  
 R 100  is C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 R 115  groups, wherein 
 R 115  at each occurrence is independently halogen, —OH, —NH—SO 2 —(C 1 -C 6  alkyl), C 1 -C 6  alkoxy or C 1 -C 6  haloalkoxy;  
 R is H or C 1 -C 4  alkyl;  
 
   W is —(CH 2 ) 0-4 —, —O—, —S(O) 0-2 —, —N(R 135 )—, or —C(O)—;    R 145  is C 1 -C 6  alkyl or CF 3 ;    R C  is —CH 2 -phenyl, which is optionally substituted with 1, 2, 3, or 4 R 200 , wherein 
 R 200  at each occurrence is independently selected from the group consisting of C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 R 205  groups; OH; alkoxy, —NO 2 ; halogen; —CO 2 H; C≡N; and  
 R 205  at each occurrence is independently selected from the group consisting of C 1 -C 6  alkyl, halogen, —OH, O-phenyl, —SH, —C≡N, —CF 3 , C 1 -C 6  alkoxy, NH 2 , NH(C 1 -C 6  alkyl), and N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl).  
   
     
     
         8 - 21 . (canceled)  
     
     
         22 . A compound according to  claim 1 , wherein 
 R C  is benzyl substituted with at least one R 200 ; wherein 
 R 200  is C 1 -C 4  alkyl, halogen, or C 1 -C 4  alkoxy; or  
   R C  is                          which is substituted with at least one R 200 ;    R N  is —C(═O)—R 100 ; wherein 
 R 100  is phenyl, C 1 -C 5  alkyl or oxazol-4-yl, wherein the phenyl and the oxazol-4-yl groups are optionally substituted with 1 or 2 groups independently selected from —OH, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, halogen, —C≡N, —SO 2 R 145 , —C(O)NRR, and —N(R)(SO 2 R 145 ); or  
 R 100  is -phenyl-oxazolyl or -phenyl-thiazolyl, wherein  
 R at each occurrence is independently H or C 1 -C 4  alkyl;  
 R 145  is C 1 -C 6  alkyl; or  
   R N  is hydrogen or C 1 -C 4  alkanoyl;    A is phenyl, or naphthyl each of which is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 6  alkyl, —O—(C 1 -C 6  alkyl), C 3 -C 6  cyclolalkyl-C 1 -C 4  alkyl, and —N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl);    E is a bond or C 1 -C 3  alkylene;    K is —(CR 4 R 5 ) n —; wherein 
 n is 0, 1, or 2;  
   L is a bond, —O—, or —N(R)— where R is hydrogen or C 1 -C 4  alkyl;    G is C 1 -C 10  alkyl, optionally substituted with up to three groups independently selected from 
 (A) halogen,  
 (B) —OH,  
 (C) C 1 -C 6  alkoxy,  
 (D) C 1 -C 6  haloalkyl; and  
   W is —(CH 2 ) 0-4 —, —O—, —S(O) 0-2 —, —N(R 135 )—, or —C(O)—.    
     
     
         23 . A compound according to  claim 22 , wherein 
 R K  is H; and    R C  is 3-methoxybenzyl.    
     
     
         24 . A compound according to  claim 23 , wherein 
 G-L-A-E-W is of the formula                          wherein the phenyl ring is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 4  alkyl, —O—(C 1 -C 4  alkyl), and —N—(C 1 -C 4  alkyl)(C 1 -C 4  alkyl); and    R J  and R K  are both H.    
     
     
         25 - 28 . (canceled)  
     
     
         29 . A compound according to  claim 1 , wherein the compound is selected from the group consisting of 
 (2R,3S)-3-amino-4-(2-butoxyphenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol,    (2R,3S)-3-amino-4-(3-butoxyphenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol,    (2R,3S)-3-amino-4-(4-butoxyphenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol,    (2R,3S)-3-amino-1-[(3-ethylbenzyl)amino]-4-[2-(hexyloxy)phenyl]butan-2-ol,    (2R,3S)-3-amino-1-[(3-ethylbenzyl)amino]-4-[3-(hexyloxy)phenyl]butan-2-ol,    (2R,3S)-3-amino-1-[(3-ethylbenzyl)amino]-4-[4-(hexyloxy)phenyl]butan-2-ol,    N-{(1S,2R)-1-(2-butoxybenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}acetamide,    N-{(1S,2R)-1-(3-butoxybenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}acetamide,    N-{(1S,2R)-1-(4-butoxybenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}acetamide,    N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[2-(hexyloxy)benzyl]-2-hydroxypropyl}acetamide,    N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[3-(hexyloxy)benzyl]-2-hydroxypropyl}acetamide,    N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[4-(hexyloxy)benzyl]-2-hydroxypropyl}acetamide,    N-{(1S,2R)-1-(2-butoxybenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,    N-{(1S,2R)-1-(3-butoxybenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,    N-{(1S,2R)-1-(4-butoxybenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,    N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[2-(hexyloxy)benzyl]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,    N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[3-(hexyloxy)benzyl]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,    N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[4-(hexyloxy)benzyl]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide,    N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[2-(hexyloxy)benzyl]-2-hydroxypropyl}-3-(1,3-oxazol-2-yl)benzamide    N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[3-(hexyloxy)benzyl]-2-hydroxypropyl}-3-(1,3-oxazol-2-yl)benzamide, and    N-{(1S,2R)-3-[(3-ethylbenzyl)amino]-1-[4-(hexyloxy)benzyl]-2-hydroxypropyl}-3-(1,3-oxazol-2-yl)benzamide.    
     
     
         30 . A compound of formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein 
 A is phenyl, optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 6  alkyl, —O—(C 1 -C 6  alkyl), C 3 -C 6  cycloalkyl C 1 -C 4  alkyl, and —N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl) or C 1 -C 6  haloalkyl;  
 R Q  is H or C 1 -C 6  alkyl optionally substituted with 1, 2, or 3 groups that are independently F, Cl, Br, I, —CN, —CF 3 , or —OH;  
 W is —(CH 2 ) 0-4 —;  
 R P  is phenyl, optionally substituted with 1, 2, 3, or 4 R 200 , wherein 
 R 200  is halogen, C 1 -C 4  alkoxy, or C 1 -C 4  alkyl optionally substituted with 1, 2, or 3 groups that are independently F, Cl, Br, I, —CN, —CF 3 , or —OH;  
 
 R 2  and R 3  at each occurrence are independently selected from the group consisting of H or C 1 -C 4  alkyl; or  
 R 2  and R 3  are taken together with the carbon to which they are attached to form a carbocycle of 3-6 carbon atoms;  
 R J  is H, C 1 -C 4  alkoxycarbonyl, or benzyloxycarbonyl;  
 R K  is H, or C 1 -C 4  alkoxycarbonyl;  
 R 4  is at each occurrence is H or C 1 -C 3  alkyl optionally substituted with 1, 2, or 3 groups that are independently F, Cl, Br, I, —CN, —CF 3 , or —OH.  
 
     
     
         31 - 42 . (canceled)  
     
     
         43 . A compound according to  claim 1 , wherein the compound is N-[(1S)-1-((1R)-2-{[1-(3-bromophenyl)cyclopropyl]amino}-1-hydroxyethyl)-3-methyl-4-phenylbutyl]acetamide hydrochloride.  
     
     
         44 . A compound of formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein 
 A is phenyl, optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 6  alkyl, —O—(C 1 -C 6  alkyl), and —N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl) or C 1 -C 6  haloalkyl;  
 W is —(CH 2 ) 0-4 —;  
 R 4  is H or C 1 -C 3  alkyl optionally substituted with 1, 2, or 3 groups that are independently F, Cl, Br, I, —CN, —CF 3 , or —OH;  
 R P  is an amine protecting group selected from the group consisting of t-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), t-butyl-dimethylsilyl (TBDMS).  
 
     
     
         45 . A compound of formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein 
 A is phenyl, optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 6  alkyl, —O—(C 1 -C 6  alkyl), and —N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl) or C 1 -C 6  haloalkyl;  
 W is —(CH 2 ) 0-4 —;  
 R 4  is H or C 1 -C 3  alkyl optionally substituted with 1, 2, or 3 groups that are independently F, Cl, Br, I, —CN, —CF 3 , or —OH;  
 R P  is an amine protecting group selected from the group consisting of t-butyloxycarbonyl (Boc), benzyloxycarbonyl(Cbz), t-butyl-dimethylsilyl (TBDMS);  
 R T  is selected from the group consisting of tosylate, mesylate, triflate, and brosylate.  
 
     
     
         46 . A compound according to  claim 1 , wherein the compound is 
 N-[(1S)-1-((1S)-2-[(4-methylphenyl)sulfonate]-1-hydroxyethyl)-3-methyl-4-phenylbutyl]-t-butylcarbamate;    N-[(1S)-1-((1S)-2-hydroxy-1-hydroxyethyl)-3-methyl-4-phenylbutyl]-t-butylcarbamate.    
     
     
         47 . A compound of formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein 
 A is phenyl, optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, C 1 -C 6  alkyl, —O—(C 1 -C 6  alkyl), and —N—(C 1 -C 6  alkyl)(C 1 -C 6  alkyl) or C 1 -C 6  haloalkyl;  
 W is —(CH 2 ) 0-4 —;  
 R 4  is C 1 -C 3  alkyl optionally substituted with 1, 2, or 3 groups that are independently F, Cl, Br, I, —CN, —CF 3 , or —OH;  
 R P  is an amine protecting group selected from the group consisting of t-butyloxycarbonyl (Boc), benzyloxycarbonyl(Cbz), t-butyl-dimethylsilyl (TBDMS).  
 
     
     
         48 . A compound according to  claim 47 , wherein the compound is N-[(1S)-1-((1S)-oxiran-1-yl)-3-methyl-4-phenylbutyl]-t-butylcarbamate.  
     
     
         49 . A pharmaceutical composition comprising a compound or salt according to  claim 1  and at least one pharmaceutically acceptable carrier, solvent, adjuvant, additive or excipient.  
     
     
         50 . A method of treating humans or animals suffering from Alzheimer's disease, MCI (mild cognitive impairment), Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, single and recurrent lobal hemorrhages, dementia, dementia of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, and diffuse Lewy body type Alzheimer's disease, comprising treating a patient in need of such treatment with a therapeutically effective amount of a compound of formula 1.