Oxadiazole derivatives and drugs containing these derivatives as the active ingredient

Abstract

An oxadiazole derivative of formula (I) and a non-toxic salt thereof, wherein R is hydrogen, alkyl, CycA, etc.; AA 1 is a single bond, amino acid residue, etc.; AA 2 is a single bond, amino acid residue, etc.; R 7 and R 8 are hydrogen, alkyl, etc.; R 9 is hydrogen, alkyl, etc.; R 10 is hydrogen, alkyl, etc.). The compound of formula (I) has an inhibitory activity against cysteine protease and therefore it is useful as an agent for the prophylaxis and/or treatment of inflammatory diseases, diseases induced by apoptosis, diseases induced by disorders of immune responses, autoimmune diseases, diseases induced by decomposition of proteins which compose organism, shock, circulatory system disorders, blood coagulation system disorders, malignant tumors, acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC), parasitic diseases, nerve degeneration diseases, pulmonary disorders, bone resorption diseases, endocrinesthenia, etc.

1 . An oxadiazole compound of formula (I),  
     
       
         
         
             
             
         
       
     
     wherein R is 
 (i) hydrogen,  
 (ii) C1-8 alkyl,  
 (iii) CycA,  
 (iv) C1-8 alkyl substituted with a group selected from halogen atom, CycA, nitro, CF 3  and cyano,  
                     
 CycA is mono-, bi- or tri-cyclic C3-15 carboring or mono-, bi- or tri-cyclic 3-15 membered heteroring comprising 1-4 of nitrogen, 1-2 of oxygen and/or 1 of sulfur;  
 R 16  is  
 (1) C1-8 alkyl,  
 (2) C2-8 alkenyl,  
 (3) C2-8 alkynyl,  
 (4) CycA or  
 (5) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with a group selected from halogen, nitro, CF 3 , cyano, CycA, NR 18 R 19  and —NHC(O)-CycA;  
 R 17 , R 18  and R 19  each independently are, hydrogen or C1-4 alkyl,  
 AA 1  is  
 (i) a single bond, or  
                     
 wherein R 1  and R 2  are the same or different to represent  
 (i) hydrogen,  
 (ii) C1-8 alkyl,  
 (iii) CycA or  
 (iv) C1-8 alkyl substituted with 1-5 of group selected from the following (1)˜(8):  
 (1) —NR 21 R 22 ,  
 (2) —OR 23 ,  
 (3) —SR 24 ,  
 (4) —COR 25 ,  
 (5) —NR 26 CONR 21 R 22 ,  
 (6) guanidino,  
 (7) CycA,  
 (8) —NR 26 SO 2 R 21 ; or  
 R 1  and R 2  are taken together to form C2-8 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or —NR 20 — and the alkylene may be substituted with —NR 21 R 22  or —OR 23 ,  
 R 20  is hydrogen, C1-4 alkyl, —COO—(C1-4 alkyl), phenyl or C1-4 alkyl substituted with phenyl,  
 R 21 , R 22 , R 23 , R 24  and R 26  are the same or different to represent hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl,  
 R 25  is C1-4 alkyl, phenyl, —NR 21 R 22 , wherein all symbols are the same meanings as above, —OR 23 , wherein R 23  is the same meaning as above, or C1-4 alkyl substituted with phenyl,  
 R 3  is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl or  
 R 3  is taken together with R 1  to form C2-6 alkylene wherein one carbon atom may be replaced by oxygen, sulfur or —NR 20 — and the alkylene may be substituted with —NR 21 R 22  or —OR 23 , or  
 when AA 1  is  
                     
 AA 1  and R may be taken together to form  
                     
 is a 5-12 membered mono- or bi-cyclic heteroring and the other symbols are the same meanings as above  
 AA 2  is  
 (i) a single bond,  
                     
 wherein R 4  and R 5  are the same or different to represent  
 (1) hydrogen,  
 (2) C1-8 alkyl,  
 (3) CycA or  
 (4) C1-8 alkyl substituted with 1-5 of group selected from the following (a)˜(h):  
 (a) —NR 41 R 42 , (b) —OR 43 , (c) —SR 44 , (d) —COR 45 , (e) —NR 46 CONR 41 R 42 , (f) guanidino, (g) CycA, (h) —NR 46 SO 2 R 41 ; or R 4  and R 5  are taken together to form C2-8 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or —NR 40 — and the alkylene may be substituted with —NR 41 R 42  or —OR 43 ,  
 R 40  is hydrogen, C1-4 alkyl, —COO—(C1-4 alkyl), phenyl or C1-4 alkyl substituted with phenyl,  
 R 41 , R 42  , R 43 , R 44  and R 46  are the same or different to represent hydrogen, C1-4 alkyl phenyl or C1-4 alkyl substituted with phenyl,  
 R 45  is C1-4 alkyl, phenyl, —NR 41 R 42 , wherein all symbols are the same meaning as above, —OR 43 , wherein R 43  is the same menaing as above, or C1-4 alkyl subbstituted with phenyl,  
 R 6  is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl or  
 R 6  is taken together with R 4  to form C2-6 alkylene wherein one carbon atom may be replaced by oxygen, sulfur or —NR 40 — and the alkylene may be substituted with —NR 41 R 42  or —OR 43 ,  
 R 48  is hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl or  
 when AA 1  is a single bond, R 48  and R may be taken together to form C2-6 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or —NR 47 —, wherein R 47  is hydrogen or C1-4 alkyl,  
 CycC is a 3-17 membered mono- or bi-cyclic heteroring,  
 CycD is a C3-14 mono- or bi-cyclic carboring or a 3-14 membered mono- or bi-cyclic heteroring, or  
 AA 2  and AA 1  are taken together to form  
                     
 wherein CycE is a 4-18 membered mono- or bi-cyclic heteroring, CycF is a 5-8 membered monocyclic heteroring, and the other symbols are the same meanings as above,  
 R 7  and R 8  are the same or different to represent  
 (i) hydrogen,  
 (ii) C1-8 alkyl,  
 (iii) CycA or  
 (iv) C1-8 alkyl substituted with 1-5 of group selected from the following (1)˜(8);  
 (1) —NR 61 R 62 , (2) —OR 63 , (3) —SR 64 , (4) —COR 65 , (5) —NR 66 CONR 61 R 62 , (6) guanidino,  
 (7) CycA, (8) —NR 66 SO 2 R 61 , or  
 R 7  and R 8  are taken together to form C2-8 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or —NR 60 — and the alkylene may be substituted with —NR 61 R 62  or —OR 63 ,  
 R 60  is hydrogen, C1-4 alkyl, —COO—(C1-4 alkyl), phenyl or C1-4 alkyl substituted with phenyl,  
 R 61 , R 62 , R 63 , R 64  and R 66  are the same or different to represent hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl, R 65  is C1-4 alkyl, phenyl, —NR 61 R 62 , wherein a symbols are the same meanings as above, —OR 63 , wherein R 63  is the same meaning as above, or C1-4 alkyl substituted with phenyl,  
 R 9  is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl or  
 R 9  is taken together with R 7  to form C2-6 alkylene wherein one carbon atom may be replaced by oxygen, sulfur or —NR 60 — and the alkylene may be substituted with —NR 61 R 62  or —OR 63 ,  
                     
 R 10  is  
 (i) C1-8 alkyl,  
 (ii) C2-8 alkenyl,  
 (iii) CycA,  
 (iv) —COR 71  or  
 (v) C1-8 alkyl substituted with 1-3 of group selected from CycA, guanidino, —COR 71 , —NR 72 R 73 , —OR 74 , cyano or —P(O)(OR 78 ) 2 ,  
 wherein R 71  is  
 (1) C1-4 alkyl,  
 (2) C1-4 alkoxy,  
 (3) CycA,  
 (4) —O-CycA,  
 (5) —NR 72 R 73 ,  
 (6) C1-4 alkyl substituted with CycA,  
 (7) C1-4 alkoxy substituted with CycA, or  
 (8) hydroxy,  
 R 72  and R 73  are the same or different to represent hydrogen, C1-8 alkyl, CycA or C1-8 alkyl substituted with CycA,  
 R 74  is  
 (1) hydrogen,  
 (2) C1-8 alkyl,  
 (3) CycA,  
 (4) C1-8 alkyl substituted with —SiR 75 R 76 R 77 , wherein R 75 , R 76  and R 77  are the same or different to represent C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl, or  
 (5) C1-8 alkyl substituted with CycA,  
 R 78  is C1-8 alkyl, phenyl, or C1-8 alkyl substituted with phenyl;  
 and, CycA is included in R, R 1 , R 2 , R 4 , R 5 , R 7 , R 8 , R 16  are the same or different and CycA, CycB, CycC, CycD, CycE and CycF, independently, may be substituted with 1-5 of R 27 :  
 R 27  is  
 (1) C1-8 alkyl,  
 (2) halogen,  
 (3) —NR 11 R 12 ,  
 (4) —OR 13 ,  
 (5) a C5-10 mono-or bi-cyclic carboring,  
 (6) nitro,  
 (7) CF 3 ,  
 (8) cyano,  
 (9) a 5-10 membered mono- or bi-cyclic heteroring  
 (10) —SR 14 ,  
 (11) —COR 15 ,  
 (12) oxo,  
 (13) —SO 2 R 15 ,  
 (14) —OCF 3  or  
 (15) C1-8 alkyl substituted with 1-5 of group selected from the following (a)˜(m):  
 (a) halogen, (b) —NR 11 R 12 , (c) —OR 13 , (d) a C5-10 mono- or bi-cyclic carboring, (e) nitro, (f) CF 3 , (g) cyano, (h) a 5-10 membered mono- or bi-cyclic heteroring, (j) —SR 14 , (k) —COR 15 , (l) —SO 2 R 15 , or (m) —OCF 3 ,  
 wherein R 11  and R 12  are the same or different to represent hydrogen, C1-4 alkyl, —COO—(C1-4 alkyl), phenyl or C1-4 alkyl substituted with phenyl,  
 R 13  and R 14  are the same or different to represent hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl  
 R 15  is C1-4 alkyl, phenyl, —NR 11 R 12 , wherein all symbols are the same meanings as above, —OR 13 , wherein R 13  is the same meaning as above, or C1-4 alkyl substituted with phenyl;  
 or a non-toxic salt thereof.  
 
   
   
       2 . The compound according to  claim 1 , wherein 
 R is (i) hydrogen,    (ii) C1-8 alkyl,    (iii) CycA,    (iv) C1-8 alkyl substituted with CycA or nitro,                          R 16  is    (1) C1-8 alkyl,    (2) C2-8 alkenyl,    (3) C2-8 alkynyl,    (4) CycA,    (5) C1-8 alkyl substituted with CycA or —NHC(O)-CycA,    (6) C2-8 alkenyl substituted with CycA,    (7) C2-8 alkynyl substituted with CycA,    AA 1  is    (i) a single bond,                          or taken together with R to represent                          wherein J 1  is oxygen, sulfur, —NR 29 —, wherein R 29  is hydrogen, C1-4 alkyl CycA or C1-4 alkyl substituted with CycA, C1-3 alkylene or C2-3 alkenylene,    J 2  is a single bond or C1-2 alkylene,    Y 2  is —N═CH—, —CH═N— or C1-2 alkylene,    J 3  is carbonyl or C1-3 alkylene,    Y 3  is C1-3 alkylene, oxygen or —NR 29 —, wherein R 29  is the same meaning as above,    R 28  is hydrogen, C1-4 alkyl, CycA or C1-4 alkyl substituted with CycA, or    R 28  is taken together with R 1  to form C2-4 alkylene, and the other symbols are the same meanings as defined in  claim 1) ,    AA 2  is    (i) a single bond,                          wherein J 4 , Y 4 , L 4  are the same or different to represent a single bond or C1-3 alkylene (with the proviso that J 4 , Y 4  and L 4  do not represent a single bond at the same time,    J 5  is C1-6 alkylene,    Y 5  is a single bond, C1-3 alkylene or —NR 67 —, wherein R 67  is hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl,    J 8  is C1-5 alkylene, wherein one carbon atom may be replaced by oxygen,    Y 8  is a single bond or C1-4 alkylene,    L 8  is —N— or —CH—,    J 6  and Y 6  are the same or different to represent a single bond or C1-3 alkylene (with the proviso that J 6  and Y 6  do not represent a single bond at the same time),    J 7  is C1-6 alkylene wherein one carbon atom may be replaced by oxygen, sulfur or —NR 67 —, wherein R 67  is the same meaning as above,    J 9  is C1-3 alkylene, oxygen, sulfur or —NR 67 —, wherein R 67  is the same meaning as above, and each ring may be substituted with 1-5 of R 27 , or    AA 2  and AA 1  are taken together to form                          wherein   is a single bond or a double bond,    J 10  and Y 10  are the same or different to represent a single bond or C1-3 alkylene,    L 10  is a single bond, C1-3 alkylene, —NR 57 —, wherein R 57  is hydrogen, C1-4 alkyl phenyl or C1-4 alkyl substituted with phenyl, —N═, oxygen or —S(O) p —, wherein p is o or an integer of 1”2,    J 12  and J 12  are the same or different to represnet a single bond or C1-3 alkylene,    L 12  is C1-3 alkylene, —NR 57 — wherein R 57  is the same meaning as above, —N═, ═N—, oxygen or —S(O) p —, wherein p is the same meaning as above,    and the other symbols are the same meanings as defined in  claim 1 , and each ring may be substituted with 1-5 of R 27  and    AA 2  and AA 1  are taken together to form                          wherein J 11  is carbonyl or C2-4 alkylene and the other symbols are the same meanings as defined in  claim 1 , and    R 27  in CycA is    (1) C1-8 alkyl,    (2) halogen,    (3) —NR 11 R 12 ,    (4) —OR 13 ,    (5) phenyl,    (6) nitro,    (7) CF 3 ,    (8) cyano,    (9) tetrazole,    (10) —SR 14 ,    (11) —COR 15 ,    (12) oxo, or    (13) C1-8 alkyl substituted with 1-5 group selected from the following (a)˜(k): 
 (a) halogen, (b) —NR 11 R 12 , (c) —OR 13 , (d) phenyl, (e) nitro, (f) CF 3 , (g) cyano, (h) tetrazole, (j) —SR 14 , or (k) —COR 15 ,  
   wherein all symbols are the same meanings as above, and    R 10  is    (i) C1-8 alkyl,    (ii) CycA,    (iii) —COR 71  or    (iv) C1-8 alkyl substituted with CycA, guanidino, —COR 71 , —NR 72 R 73  or OR 74 ,    wherein all symbols are the same meanings as defined in  claim 1 , or a non-toxic salt thereof.    
   
   
       3 . The compound according to  claim 2 , 
 wherein R is C1-8 alkyl or C1-8 alkyl substituted with CycA or nitro,                          and    AA 1  is a single bond, or                          and    AA 2  is a single bond,                          or a non-toxic salt thereof.    
   
   
       4 . The compound according to  claim 3 , 
 wherein R 16  is C1-8 alkyl C2-8 alkenyl, C2-8 alkynyl, CycA, or C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with CycA and therein CycA is a C5-10 mono- or bi-cyclic carboaryl or partially or completely saturated one thereof or a 5-10 membered heteroaryl or partially or completely saturated one thereof containing 1-2 of nitrogen, 1-2 of oxygen and/or 1 of sulfur,    R 1  is hydrogen, C1-8 alkyl, phenyl, or C1-8 alkyl substituted with NH 2 , C1-4 alkoxy, SH, SCH 3 , phenyl, hydroxyphenyl, COOH, CONH 2 , guanidino, imidazole or indole and R 2  is hydrogen or R 1  and R 2  are taken together to form C3-6 alkylene,    R 3  is hydrogen or C1-4 alkyl or R 3  and R 1  are taken together to form C2-4 alkylene,    AA 2  is a single bond,                          R 4  is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with NH 2 , C1-4 alkoxy, SH, SCH 3 , phenyl, hydroxyphenyl, COOH, CONH 2 , guanidino, imidazole or indole and R 5  is hydrogen or R 4  and R 5  are taken together to form C3-6 alkylene,    R 6  is hydrogen or C1-4 alkyl, or R 6  and R 4  are taken together to form C2-4 alkylene,    R 48  is hydrogen or C1-4 alkyl,    R 7  is hydrogen, C1-8 alkyl, phenyl, or C1-8 alkyl substituted with NH 2 , C1-4 alkoxy, SH, SCH 3 , phenyl, hydroxyphenyl, COOH, CONH 2 , guanidino, imidazole or indole and R 8  is hydrogen or R 7  and R 8  are taken together to form C3-6 alkylene,    R 9  is hydrogen or C1-4 alkyl, or R 9  and R 7  are taken together to form C2-4 alkylene,    or a non-toxic salt thereof.    
   
   
       5 . The compound according to  claim 1 , wherein R 16  is C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with a group selected from halogen, nitro, CF 3 , cyano and NR 18 R 19 , or a non-toxic salt thereof.  
   
   
       6 . The compound according to  claim 1 , 
 wherein R 16  is    (1) CycA containing 1-5 of substituent R 27  or    (2) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with CycA containing 1-5 or substituent R 27 ,    wherein at least one of R 27  in (1) and (2) is selected from    (i) a C5-10 mono- or bi-carboring,    (ii) a 5-10 membered mono- or bi-cyclic heteroring,    (iii) —SO 2 R 15 ,    (iv) —OCF 3 , and    (v) C1-8 alkyl substituted with 1-5 of group selected from (a) halogen, (b) —NR 11 R 12 , (c) —OR 13 , (d) a C5-10 mono- or bi-cyclic carboring, (e) nitro, (f) CF 3 , (g) cyano, (h) a 5-10 membered mono- or bi-cyclic heteroring (j) —SR 14 , (k) —COR 15 , (l) —SO 2 R 15  and (m) —OCF 3 , wherein at least one of them is selected from a C5-10 mono- or bi-cyclic carboring, a 5-10 membered mono- or bi-cyclic heteroring, —SO 2 R 15  and —OCF 3 , or a non-toxic salt thereof.    
   
   
       7 . The compound according to  claim 1 , 
 wherein R 10  is C1-8 alkenyl, or C1-8 alkyl substituted with 1-3 of the group selected from CyCA, guanidino, COR 71 , NR 72 R 73 , OR 74 , cyano or P(O)(OR 78 ) 2  (with the proviso that the substituent is one, then it is not CycA, guanidino, COR 71 , NR 72 R 73 , or OR 74 ), or a non-toxic salt thereof.    
   
   
       8 . The compound according to  claim 1 , wherein AA 1  is a single bond, and R 48  and R are taken together to form C2-6 alkylene, wherein one carbon atom may be replaced by —NR 47 —, wherein R 47  is the same meaning as defined in  claim 1 , oxygen or sulfur, or a non-toxic salt thereof.  
   
   
       9 . The compound according to  claim 1 , wherein Z ring is  
     
       
         
         
             
             
         
       
     
   
   
       10 . The compound according to  claim 1 , wherein Z ring is  
     
       
         
         
             
             
         
       
     
   
   
       11 . The compound according to  claim 1 , wherein Z ring is  
     
       
         
         
             
             
         
       
     
   
   
       12 . (canceled)  
   
   
       13 . The compound according to  claim 1 , which is 
 (1) (2S)-N-[(2S)-2-(4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (2) (2S)-N-[4-methyl-1-(3-methyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (3) (2S)-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (4) (2S)-N-[(2S)-4-methyl-1-(3-methoxymethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (5) (2S)-N-[(2S)-1-(3-butyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (6) (2S)-N-[(2S)-1-(3-benzyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (7) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-propyl-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (8) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-pentyl-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (9) (2S)-N-[(2S)-4-methyl-1-(3-(1-methylethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (10) (2S)-N-[(2S)-1-(3-ethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (11) (2S)-N-[(2S)-1-(3-cyclohexylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (12) (2S)-N-[(2S)-1-(3-cyclohexyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (13) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-(3-phenylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (14) (2S)-N-[4-methyl-1-oxo-1-(3-(2-trimethylsilylethoxymethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (15) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-phenethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (16) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-(thiophen-3-ylmethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (17) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-(thiophen-2-ylmethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (18) (2S)-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (19) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-(pyridin-2-ylmethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (20) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-(pyridin-3-ylmethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (21) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-(pyridin-4-ylmethyl)-2-oxo-1,3,4-oxadiazoin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (22) (2S)-N-[(2S)-1-(3-cyclobutylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (23) (2S)-N-[(2S)-1-(3-cyclopentylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (24) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]cyclohexylcarboxamide,    (25) N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]benzyloxycarboxamide,    (26) 1-[(1S,2R)-2-benzoylaminocyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (27) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-4-benzyloxybenzamide,    (28) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-3-benzyloxybenzamide,    (29) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-2-benzyloxybenzamide,    (30) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (31) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]cinnamamide[cinnamoylamide],    (32) 2-methylpropoxy-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (33) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]benzamide,    (34) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-3-cyclopentylpropionylamide,    (35) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]benzenesulfonylamide,    (36) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (37) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-2-benzoylaminobenzamide,    (38) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-[(2S)-N-benzoylpiperidin-2-yl]carboxamide,    (39) N-[4-methyl-2-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-oxo-2-pentyl]-1-[(2S)-N-phenethylpiperidin-2-yl]carboxamide,    (40) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-[(2S)-N-benzylpiperidin-2-yl]carboxamide,    (41) N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-[(2S)-N-phenacylpiperidin-2-yl]carboxamide,    (42) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-[(2S)-N-benzylcarbonylpiperidin-2-yl]carboxamide,    (43) N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-[(3R)-N-benzoylpiperidin-3-yl]carboxamide,    (44) N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-[(3R)-N-benzylpiperidin-3-yl]carboxamide,    (45) N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-[(2S)-N-(3-phenylpropyl)piperidin-2-yl]carboxamide,    (46) N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-[(2S)-N-phenethylpiperidin-2-yl]carboxamide,    (47) N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-[(2S)-N-(4-phenylbutyl)piperidin-2-yl]carboxamide,    (48) N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-1-(2-benzyloxycyclohexyl)carboxamide,    (49) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (50) t-butoxy-N-[4-methyl-1-oxo-1-(3-(2-trimethylsilylethoxymethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]carboxamide,    (51) (2S)-2-amino-4-methyl-1-[3-(2-trimethylsilylethoxymethyl)-2-oxo-1,3,4-oxadiazolin-5-yl]pentanone,    (52) 1-[(1S,2R)-2-benzoylaminocyclohexyl]-N-[4-methyl-1-oxo-1-(3-(2-trimethylsilylethoxymethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]carboxamide,    (53) 1-[(1S,2R)-2-benzoylaminocyclohexyl]-N-[1-(3-hydroxymethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (54) 1-[(1S,2R)-2-benzoylaminocyclohexyl]-N-[(2S)-3-methyl-1-(3-methyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-butyl]carboxamide,    (55) 1-[(1S,2R)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-butyl-2-oxo-1,3,4-oxadiazolin-5-yl)-3-methyl-1-oxo-2-butyl]carboxamide,    (56) 1-[(1S,2R)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-hexyl]carboxamide,    (57) 1-[(1S,2R)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-4-phenyl-2-butyl]carboxamide,    (58) (2S)-N-[(2S)-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-hexyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (59) (2S)-N-[(2S)-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-4-phenyl-2-butyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (60) 1-[(1R,2S)-2-(4-nitrobenzoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (61) 1-[(1R,2S)-2-(4-methoxybenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (62) 1-[(1R,2S)-2-(naphthalen-2-ylcarbonylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (63) 1-[(1R,2S)-2-(quinoxalin-2-ylcarbonylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (64) 1-[(1R,2S)-2-(4-chlorobenzoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (65) 1-[(1R,2S)-2-(benzo[b]thiophen-2-ylcarbonylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(1-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (66) 1-[(1R,2S)-2-(4-fluorobenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (67) 1-[(1R,2S)-2-(4-t-butylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(1-(1-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (68) 1-[(1R,2S)-2-(pyridin-2-ylcarbonylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (69) 1-[(1R,2S)-2-(naphthalen-1-ylmethylcarbonylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (70) 1-[(1R,2S)-2-(2-fluorobenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (71) 1-[(1R,2S)-2-(4-phenylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (72) 1-[(1R,2S)-2-(2-chloropyridin-5-ylcarbonylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-( 2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (73) 1-[(1R,2S)-2-(2-methylthiopyridin-3-ylcarbonylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (74) 1-[(1R,2S)-2-(4-cyanobenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (75) 1-[(1R,2S)-2-(4-dimethylaminobenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (76) [(2S)-N-phenethylpyrrolidin-2-yl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (77) [(2S)-N-(3-phenylpropyl)pyrrolidin-2-yl]-N-[1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (78) [(2R)-N-phenethylpyrrolidin-2-yl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (79) 1-[(1R,2S)-2-(4-dimethylaminomethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (80) [(2R)-2-phenylaminocarbonylpiperidino]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (81) 1-[(1R,2S)-2-benzoylaminocyclopentyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (82) 1-[(1R,2S)-2-(4-dimethylaminomethyl-2-fluorobenzoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (83) 1-[(1R,2S)-2-(3-dimethylaminomethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (84) 1-[(1S,2R)-2-benzoylaminocyclopentyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (85) 1-[(1R,2S)-2-(2-dimethylaminomethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (86) 1-[(1R,2S)-2-(4-methylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (87) 1-[(1R,2S)-2-(3-methylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (88) 1-[(1R,2S)-2-(2-methylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (89) 1-[(1R,2S)-2-(3-chlorobenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (90) 1-[(1R,2S)-2-(2-chlorobenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (91) 1-[(1R,2S)-2-(3-fluorobenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (92) 1-[(1R,2S)-2-(2-methoxybenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (93) 1-[(1R,2S)-2-(3-methoxybenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (94) 1-[(1R,2R)-2-benzoylaminocyclopentyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (95) 1-[(1S,2S)-2-benzoylaminocyclopentyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (96) 1-[(1R,2S)-2-(4-dimethylaminomethyl-3-fluorobenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (97) (4-dimethylaminomethyl)-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]benzamide,    (98) (3-dimethylaminomethyl)-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]benzamide,    (99) 1-[(1R,2S)-2-(2-dimethylaminomethyl-4-fluorobenzoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (100) (2-dimethylaminomethyl)-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]benzamide,    (101) 2-phenyl-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]benzamide,    (102) 1-(1-benzoylaminocyclohexyl)-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (103) 1-[(1R,2S)-2-(4-dimethylaminomethylbenzoylamino)cyclohexyl]-N-[1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (104) 1-[(1R,2S)-2-(4-fluorobenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (105) 1-[(1R,2S)-2-(4-chlorobenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (106) 1-[(1R,2S)-2-(4-methoxybenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (107) 1-[(1R,2S)-2-(4-cyanobenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (108) 1-[(1R,2S)-2-(N-benzoyl-N-methylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (109) 1-[(1R,2S)-2-(N-(4-dimethylaminobenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (110) 1-[(1R,2S)-2-(2-fluorobenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-hexyl]carboxamide,    (111) 1-[(1R,2S)-2-(4-dimethylaminobenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-hexyl]carboxamide,    (112) 1-[(1R,2S)-2-(4-dimethylaminomethylbenzoylamino)cyclohexyl]-N-[1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-hexyl]carboxamide,    (113) 1-[(1R,2S)-2-(2-dimethylaminomethyl-4-fluorobenzoylamino)cyclohexyl]-N-[1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (114) 1-[(1R,2S)-2-(4-dimethylaminomethyl-2-fluorobenzoylamino)cyclohexyl]-N-[1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (115) 1-[(1R,2S)-2-(4-dimethylaminobenzoylamino)cyclohexyl]-N-[1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (116) 1-[(1R,2S)-2-(3-dimethylaminomethylbenzoylamino)cyclohexyl]-N-[1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (117) 1-[(1R,2S)-2-(2-dimethylaminomethylbenzoylamino)cyclohexyl]-N-[1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (118) (2S)-N-[2-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-2-oxoethyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (119) (2S)-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methoxy-1-oxo-2-butyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (120) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methoxy-1-oxo-2-butyl]carboxamide,    (121) (2S)-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-hexyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (122) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-hexyl]carboxamide,    (123) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-cyclohexyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (124) (2S)-N-[(2S)-1-(3-ethoxymethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (125) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-ethoxymethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (126) (2S)-N-[(2S)-4-methyl-1-(3-(2-methoxyethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (127) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-4-methyl-1-(3-methoxyethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (128) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-butyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (129) 1-[(1R,2S)-2-(4-fluorobenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-hexyl]carboxamide,    (130) (2S)-N-[(2S)-3-ethoxy-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5yl)-1-oxo-2-propyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (131) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-3-ethoxy-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-propyl]carboxamide,    (132) (2S)-N-[1-(3-(2-dimethylaminoethyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (133) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[1-(3-(2-dimethylamino)ethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (134) (2S)-N-[(2S)-4-methoxy-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-butyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (135) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-4-methoxy-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-butyl]carboxamide,    (136) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[2-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-oxoethyl]carboxamide,    (137) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[2-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-2-oxoethyl]carboxamide,    (138) (2S)-N-[2-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-oxoethyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (139) (2S)-N-[3-cyclopropyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-propyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (140) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[3-cyclopropyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-propyl]carboxamide,    (141) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-t-butoxycarbonylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (142) (2S)-N-[(2S)-1-(3-t-butoxycarbonylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (143) 1-[(1R,2S)-2-(2-aminopyridin-5-ylcarbonylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (144) 1-[(1R,2S)-2-(2-dimethylaminomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (145) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-4-methyl-1-oxo-1-(3-phenyl-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]carboxamide,    (146) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-phenyl-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (147) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-4-methyl-1-oxo-1-(3-carboxymethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]carboxamide,    (148) (2S)-N-[(2S)-4-methyl-1-oxo-1-(3-carboxymethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide, or    (149) 1-[(1R,2S)-2-(2-butynoylamino)cyclohexyl]-N-[4-methyl-1-oxo-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-2-pentyl]carboxamide    or a non-toxic salt thereof.    
   
   
       14 . The compound according to  claim 1 , which is 
 (1) (2S)-N-[(2S)-4-methyl-1-(5-bis(methoxycarbonyl)methylthio-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]-4-methyl-2-benzyloxycarbonylaminopentanamide,    (2) 1-[(1R,2S)-2-(4-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (3) 1-[(1R,2S)-2-(4-pyrrolidinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (4) 1-[(1R,2S)-2-(4-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-methylthio-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (5) 1-[(1R,2S)-2-(4-pyrrolidinomethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(5-methylthio-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (6) 1-[(1R,2S)-2-(3-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-methylthio-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (7) 1-[(1R,2S)-2-(3-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (8) 1-[(1R,2S)-2-(3-pyrrolidinomethylbenzoylamino)cycohexyl]-N-[(2S)-4-methyl-1-(5-methylthio-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (9) 1-[(1R,2S)-2-(3-pyrrolidinomethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(5-(1-methylethylthio)-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (10) 1-[(1R,2S)-2-(2-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-methylthio-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (11) 1-[(1R,2S)-2-(3-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (12) 1-[(1R,2S)-2-(2-pyrrolidin-1-ylmethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(5-methylthio-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (13) 1-[(1R,2S)-2-(2-pyrrolidin-1-ylmethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(5-(1-methylethylthio)-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (14) 1-[1-(4-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (15) 1-(4-benzoylamino-1-t-butoxycarbonylpiperidin-4-yl)-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide,    (16) 1-[1-(4-morpholinomethylbenzoylamino)cyclopentyl]-N-[4-methyl-1-(5-(1-methylethylthio)-1-oxo-1,3,4-oxadiazol-2-yl)-2-pentyl]carboxamide,    (17) 1-(4-benzoylamino-1-methoxycarbonylpiperidin-4-yl)-N-[(2S)-4-methyl-1-(5-( 1-methylethylthio)-1-oxo-1,3,4-oxadiazol-2-yl)-2-pentyl]carboxamide,    (18) 1-(4-benzoylamino-1,1-dimethylpiperidinium-4-yl)-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1-oxo-1,3,4-oxadiazol-2-yl)-2-pentyl]carboxamide,    (19) 1-[(1R,2S)-2-aminocyclohexyl]-N-[(2S)-4-methyl-1-(2-(1-methylethylthio)-1,3,4-oxadiazol-5-yl)-1-oxo-2-pentyl]carboxamide,    (20) 1-[(1R,2S)-2-(4-dimethylaminobut-2-ynoylamino)cyclohexyl]-N-[4-methyl-1-(2-(1-methylethylthio)-1,3,4-oxadiazol-5-yl)-1-oxo-2-pentyl]carboxamide,    (21) 1-[1-(4-dimethylaminobut-2-ynoylaminocyclohexyl)]-N-[4-methyl-1-(5-(1-methylethylthio)-1,3,4-oxadiazol-2-yl)-1-oxo-2-pentyl]carboxamide, or    (22) 1-[(1R,2S)-2-(4-morpholinobut-2-ynoylamino)cyclohexyl]-N-[4-methyl-1-(2-( 1-methylethylthio)-1,3,4-oxadiazol-5-yl)-1-oxo-2-pentyl]carboxamide    or a non-toxic salt thereof.    
   
   
       15 . The compound according to  claim 1 , which is 
 (1) piperidino-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-1-oxo-2-pentyl]carboxamide,    (2) 1-[(1R,2S)-2-(4-pyrrolidinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (3) 1-[(1R,2S)-2-(4-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (4) 1-[(1R,2S)-2-(3-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (5) 1-[(1R,2S)-2-(3-pyrrolidinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (6) 1-[(1R,2S)-2-(2-morpholinomethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-butyl]carboxamide,    (7) 1-[(1R,2S)-2-(4-pyrrolidinomethylbenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (8) 1-[(1R,2S)-2-(4-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (9) 1-[(1R,2S)-2-(3-pyrrolidinomethylbenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (10) 1-[(1R,2S)-2-(3-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (11) 1-[(1R,2S)-2-(2-morpholinomethylbenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (12) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[(2S)-1-(3-bis(methoxycarbonyl)methyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (13) (2S)-N-[(2S)-1-(3-bis(methoxycarbonyl)methyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (14) 1-[(2S)-2-phenylaminocarbonylpiperidino]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (15) 1-[(1R,2S)-2-t-butoxycarbonylaminocyclohexyl]-N-[(2S)-1-(3-((1R, 2S)-2-t-butoxycarbonylaminocyclohexylcarbonyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (16) 1-[(1R,2S)-2-(2-pyrrolidinomethylbenzoylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    (17) 1-[(1R,2S)-2-(3-pyrrolidinomethylbenzoylamino)cyclohexyl]-N-[(2S)-1-(3-cyclopropylmethyl-2-oxo-1,3,4-oxadiazolin-5-yl)-4-methyl-1-oxo-2-pentyl]carboxamide,    (18) 1-[(1R,2S)-2-(4-dimethylaminobut-2-ynoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide, or    (19) 1-[(1R,2S)-2-(4-morpholinobut-2-ynoylamino)cyclohexyl]-N-[4-methyl-1-(3-(2-methylpropyl)-2-oxo-1,3,4-oxadiazolin-5-yl)-1-oxo-2-pentyl]carboxamide,    or a non-toxic salt thereof.    
   
   
       16 . The compound according to  claim 1 , which is 
 (1) (2S)-N-[(2S)-4-methyl-1-(5-methylthio-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (2) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[4-methyl-1-(5-methylthio-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]carboxamide,    (3) 1-[(1R,2S)-2-benzoylaminocyclohexyl]-N-[4-methyl-1-(5-(1-methylethylthio)-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]carboxamide,    (4) (2S)-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]-2-benzyloxycarbonylamino-4-methylpentanamide,    (5) 1-[1-(4-dimethylaminomethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(5-(1-methylethylthio)-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]carboxamide,    (6) 1-[1-(4-morpholinomethylbenzoylamino)cyclohexyl]-N-[4-methyl-1-(5-(1-methylethylthio)-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]carboxamide,    (7) 1-[1-(pyridin-3-ylcarbonylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]carboxamide,    (8) 1-(1-morpholinocarbonylaminocyclohexyl)-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]carboxamide,    (9) 1-[1-(pyridin-4-ylcarbonylamino)cyclohexyl]-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]carboxamide, or    (10) 1-cyclohexyl-N-[(2S)-4-methyl-1-(5-(1-methylethylthio)-1,2,4-oxadiazole-3-yl)-1-oxo-2-pentyl]carboxamide,    or a non-toxic salt thereof.    
   
   
       17 . A pharmaceutical composition comprising the oxadiazole derivative of formula (I) claimed in  claim 1  or a non-toxic salt thereof.  
   
   
       18 . A cysteine protease inhibitor comprising the oxadiazole derivative of formula (I) claimed in  claim 1  or a non-toxic salt thereof as an active ingredient.  
   
   
       19 . The inhibitor according to  claim 18 , wherein cysteine protease is cathepsin K, cathepsin S, cathepsin L, cathepsin B, cathepsin H, calpain or caspase-1.  
   
   
       20 . The inhibitor according to  claim 19 , wherein cysteine protease is cathepsin K.  
   
   
       21 . The inhibitor according to  claim 19 , wherein cysteine protease is cathepsin S.  
   
   
       22 . An agent for the prophylaxis and/or treatment of inflammatory diseases, diseases induced by apoptosis, diseases induced by disorders of immune responses, autoimmune diseases, diseases induced by decomposition of proteins which compose organism, shock, circulatory system disorders, blood coagulation system disorders, malignant tumors, acquired immune deficiency syndrome and AIDS-related somplex, parasitic diseases, nerve degenerative diseases, pulmonary disorders, bone resorption diseases, endocrinesthenia, which comprises an oxadiazole derivative of formula (I) claimed in  claim 1  or a non-toxic salt thereof as an active ingredient.