PRODRUGS OF MITOCHONDRIA-TARGETING OLIGOPEPTIDES
Disclosed are various prodrugs of Elamipretide.
1 . A compound of Formula (I)
wherein:
X is —N(R 15 )—R 1 ,
Y is —N(R 15 )—R 2 ,
R 1 , R 2 , R 3 , and R 17 are independently H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, heteroalkyl, heteroaryl, T, R 9 C(O)—, R 10 OC(O)—, R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, (R 11 O)(R 12 O)P(O)—, or R 11 R 12 N(R 9 O)P(O)—;
R 4 is alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, T, a side-chain of a naturally or non-naturally occurring chiral amino acid,
R 6 and R 7 are independently H, alkyl, or acyl; or R 6 and R 7 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring;
R 8 is H, alkyl, heteroalkyl, or acyl;
R 9 , R 11 , and R 12 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, heteroarylheteroalkyl, or T;
R 11 and R 12 can be taken together to form a heterocyclic ring;
R 10 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, heteroarylheteroalkyl, or T;
R 13 is H, methyl, ethyl, isopropyl, or tert-butyl;
R 14 is independently D, F, Cl, Br, I, —CH 3 , —OCH 3 , CH 2 CH 3 , —OCH 2 CH 3 , —CCl 3 , —CF 3 , —C≡N, —OH, or —NO 2 ;
T is —(CH 2 ) w —(O) x —[(CH 2 CH 2 )—O] q —R 13 ;
n and m are independently 1, 2, 3, 4, 5, or 6;
p is 0, 1, 2, 3, 4, or 5;
q is an integer from 1-30 inclusive;
x is 0 or 1; and
w is 0, 1 or 2; provided that: if x is 0 then w is 0; and if w is 0, then x is 0;
the absolute stereochemistry at each of stereocenters 0.1, 0.2, *3 and *4 is independently R (D for an amino acid) or S (L for an amino acid); and
at least one of R 1 , R 2 , R 3 and R 17 is R 9 C(O)—, R 10 OC(O)—, R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, (R 11 O)(R 12 O)P(O)—, or R 11 R 12 N(R 9 O)P(O)—.
2 . The compound of claim 1 , wherein each of R 1 , R 2 , R 3 and R 17 is not: Cbz, Boc, Bpoc, Bhoc, Nps, Bpoc, Ddz, Fmoc, ivDde, Msc, Nsc, Bsmoc, Sps, or Esc.
3 . The compound of claim 1 or 2 , wherein X is —N(R 15 )—R 1 .
4 . The compound of claim 1 or 2 , wherein X is
5 . The compound of claim 1 or 2 , wherein X is
6 . The compound of claim 1 or 2 , wherein X is
7 . The compound of any one of claims 1 - 6 , wherein Y is —N(R 15 )—R 2 .
8 . The compound of any one of claims 1 - 6 , wherein Y is
9 . The compound of any one of claims 1 - 6 , wherein Y is
10 . The compound of any one of claims 1 - 6 , wherein Y is
11 . The compound of any one of claims 1 - 10 , wherein R 1 is H.
12 . The compound of any one of claims 1 - 10 , wherein R 1 is alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, heteroalkyl, or heteroaryl.
13 . The compound of any one of claims 1 - 10 , wherein R 1 is T.
14 . The compound of claim 13 , wherein R 1 is —[(CH 2 CH 2 )—O] q —R 13 .
15 . The compound of any one of claims 1 - 10 , wherein R 1 is R 9 C(O)—, R 10 OC(O)—, or (R 11 O)(R 12 O)P(O)—.
16 . The compound of any one of claims 1 - 10 , wherein R 1 is R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, or R 11 R 12 N(R 9 O)P(O)—.
17 . The compound of any one of claims 1 - 16 , wherein R 2 is H.
18 . The compound of any one of claims 1 - 16 , wherein R 2 is alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, heteroalkyl, or heteroaryl.
19 . The compound of any one of claims 1 - 16 , wherein R 2 is T.
20 . The compound of claim 19 , wherein R 2 is —[(CH 2 CH 2 )—O] q —R 13 .
21 . The compound of any one of claims 1 - 16 , wherein R 2 is R 9 C(O)—, R 10 OC(O)—, or (R 11 O)(R 12 O)P(O)—.
22 . The compound of any one of claims 1 - 16 , wherein R 2 is R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, or R 11 R 12 N(R 9 O)P(O)—.
23 . The compound of any one of claims 1 - 22 , wherein R 3 is H.
24 . The compound of any one of claims 1 - 22 , wherein R 3 is alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, heteroalkyl, or heteroaryl.
25 . The compound of any one of claims 1 - 22 , wherein R 3 is T.
26 . The compound of claim 25 , wherein R 3 is —[(CH 2 CH 2 )—O] q —R 13 .
27 . The compound of any one of claims 1 - 22 , wherein R 3 is R 9 C(O)—, R 10 OC(O)—, or (R 11 O)(R 12 O)P(O)—.
28 . The compound of any one of claims 1 - 22 , wherein R 3 is R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, or R 11 R 12 N(R 9 O)P(O)—.
29 . The compound of any one of claims 1 - 28 , wherein R 17 is H.
30 . The compound of any one of claims 1 - 28 , wherein R 17 is alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, heteroalkyl, or heteroaryl.
31 . The compound of any one of claims 1 - 28 , wherein R 17 is T.
32 . The compound of claim 31 , wherein R 17 is —[(CH 2 CH 2 )—O] q —R 13 .
33 . The compound of any one of claims 1 - 28 , wherein R 17 is R 9 C(O)—, R 10 OC(O)—, or (R 11 O)(R 12 O)P(O)—.
34 . The compound of any one of claims 1 - 28 , wherein R 17 is R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, or R 11 R 12 N(R 9 O)P(O)—.
35 . The compound of any one of claims 1 - 34 , wherein R 4 is alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, or arylheteroalkyl.
36 . The compound of any one of claims 1 - 34 , wherein R 4 is T.
37 . The compound of claim 36 , wherein R 4 is —(CH 2 )—(O)—[(CH 2 CH 2 )—O] q —R 13 .
38 . The compound of claim 36 , wherein R 4 is —(CH 2 ) 2 —(O)—[(CH 2 CH 2 )—O] q —R 13 .
39 . The compound of any one of claims 1 - 34 , wherein R 4 is a side-chain of a naturally or non-naturally occurring chiral amino acid.
40 . The compound of any one of claims 1 - 34 , wherein R 4 is
41 . The compound of any one of claims 1 - 34 , wherein R 4 is
42 . The compound of any one of claims 1 - 34 , wherein R 4 is
43 . The compound of claim 42 , wherein R 4 is
and each R 14 is H.
44 . The compound of any one of claims 1 - 43 , wherein R 6 is H.
45 . The compound of any one of claims 1 - 43 , wherein R 6 is alkyl or acyl.
46 . The compound of any one of claims 1 - 45 , wherein R 7 is H.
47 . The compound of any one of claims 1 - 45 , wherein R 7 is alkyl or acyl.
48 . The compound of any one of claims 1 - 43 , wherein R 6 and R 7 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring.
49 . The compound of any one of claims 1 - 48 , wherein R 8 is H.
50 . The compound of any one of claims 1 - 48 , wherein R 8 is alkyl, heteroalkyl, or acyl.
51 . The compound of any one of claims 1 - 48 , wherein R 8 is H, methyl or ethyl.
52 . The compound of any one of claims 1 - 51 , wherein R 9 is H.
53 . The compound of any one of claims 1 - 51 , wherein R 9 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, or heteroarylheteroalkyl.
54 . The compound of claim 53 , wherein R 9 is C 1 -C 8 alkyl.
55 . The compound of any one of claims 1 - 51 , wherein R 9 is T.
56 . The compound of claim 55 , wherein R 9 is —[(CH 2 CH 2 )—O] q —R 13 and q is 1-20.
57 . The compound of any one of claims 1 - 56 , wherein R 10 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, or heteroarylheteroalkyl.
58 . The compound of claim 57 , wherein R 10 is C 1 -C 8 alkyl.
59 . The compound of any one of claims 1 - 56 , wherein R 10 is T.
60 . The compound of claim 59 , wherein R 10 is —[(CH 2 CH 2 )—O] q —R 13 and q is 1-20.
61 . The compound of any one of claims 1 - 56 , wherein R 11 is H.
62 . The compound of any one of claims 1 - 56 , wherein R 11 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, or heteroarylheteroalkyl.
63 . The compound of claim 62 , wherein R 11 is C 1 -C 8 alkyl.
64 . The compound of any one of claims 1 - 56 , wherein R 11 is T.
65 . The compound of claim 64 , wherein R 11 is —[(CH 2 CH 2 )—O] q —R 13 and q is 1-20.
66 . The compound of any one of claims 1 - 65 , wherein R 12 is H.
67 . The compound of any one of claims 1 - 65 , wherein R 12 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, or heteroarylheteroalkyl.
68 . The compound of claim 67 , wherein R 12 is C 1 -C 8 alkyl.
69 . The compound of any one of claims 1 - 65 , wherein R 12 is T.
70 . The compound of claim 69 , wherein R 12 is —[(CH 2 CH 2 )—O] q —R 13 and q is 1-20.
71 . The compound of any one of claims 1 - 70 , wherein R 13 is H.
72 . The compound of any one of claims 1 - 70 , wherein R 13 is methyl, ethyl, isopropyl, or tert-butyl.
73 . The compound of any one of claims 1 - 42 and 44 - 72 , wherein R 14 is D.
74 . The compound of any one of claims 1 - 42 and 44 - 72 , wherein R 14 is F, Cl, Br, I, —CCl 3 , or —CF 3 .
75 . The compound of any one of claims 1 - 42 and 44 - 72 , wherein R 14 is —CH 3 , —OCH 3 , CH 2 CH 3 , —OCH 2 CH 3 , —OH, or —NO 2 .
76 . The compound of any one of claims 1 - 3 and 7 , wherein R 15 is H.
77 . The compound of any one of claims 1 - 3 and 7 , wherein R 15 is alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, or acyl.
78 . The compound of claim 77 , wherein R 15 is methyl, ethyl, isopropyl or tert-butyl.
79 . The compound of any one of claims 1 - 78 , wherein R 17 is H.
80 . The compound of any one of claims 1 - 78 , wherein R 17 is alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, heteroalkyl, or heteroaryl.
81 . The compound of any one of claims 1 - 78 , wherein R 17 is —(CH 2 )—(O)—[(CH 2 CH 2 )—O] q —R 13 or —(CH 2 ) 2 —(O)—[(CH 2 CH 2 )—O] q —R 13 .
82 . The compound of any one of claims 1 - 78 , wherein R 17 is R 9 C(O)—, R 10 OC(O)—, or (R 11 O)(R 12 O)P(O)—.
83 . The compound of any one of claims 1 - 78 , wherein R 17 is R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, or R 11 R 12 N(R 9 O)P(O)—.
84 . The compound of any one of claims 1 - 83 , wherein n is 1, 2, 3 or 4.
85 . The compound of any one of claims 1 - 83 , wherein n is 5, or 6.
86 . The compound of any one of claims 1 - 83 , wherein m is 1, 2, 3 or 4.
87 . The compound of any one of claims 1 - 83 , wherein m is 5, or 6.
88 . The compound of any one of claims 1 - 87 , wherein the stereochemistry at the carbon atom labeled *4 is D, the stereochemistry at the carbon atom labeled *3 is L, the stereochemistry at the carbon atom labeled *2 is L, and the stereochemistry at the carbon atom labeled *1 is L.
89 . The compound of any one of claims 1 - 87 , wherein the stereochemistry at the carbon atom labeled *4 is L, the stereochemistry at the carbon atom labeled *3 is D, the stereochemistry at the carbon atom labeled *2 is D, and the stereochemistry at the carbon atom labeled *1 is D.
90 . The compound of any one of claims 1 - 87 , wherein the stereochemistry at the carbon atom labeled *4 is D, the stereochemistry at the carbon atom labeled *3 is D, the stereochemistry at the carbon atom labeled *2 is D, and the stereochemistry at the carbon atom labeled *1 is D.
91 . The compound of any one of claims 1 - 87 , wherein the stereochemistry at the carbon atom labeled *4 is L, the stereochemistry at the carbon atom labeled *3 is L, the stereochemistry at the carbon atom labeled *2 is L, and the stereochemistry at the carbon atom labeled *1 is L.
92 . The compound of any one of claims 1 - 87 , wherein the stereochemistry at the carbon atom labeled *4 is D, the stereochemistry at the carbon atom labeled *3 is L, the stereochemistry at the carbon atom labeled *2 is D, and the stereochemistry at the carbon atom labeled *1 is L.
93 . The compound of any one of claims 1 - 87 , wherein the stereochemistry at the carbon atom labeled *4 is L, the stereochemistry at the carbon atom labeled *3 is D, the stereochemistry at the carbon atom labeled *2 is L, and the stereochemistry at the carbon atom labeled *1 is D.
94 . The compound of claim 1 , wherein the compound is
95 . The compound of claim 1 , wherein the compound is
96 . A compound of Formula (II):
wherein:
X is —N(R 15 )—,
Y is —N(R 15 )—,
W is —C(O)—, —C(S)—, —C(R 16 ) 2 —, —S(O)—, —S(O 2 )—, or —P(O)[Q(R 10 )]—;
Q is O or a bond;
R 3 and R 17 are independently H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, heteroalkyl, heteroaryl, T, R 9 C(O)—, R 10 OC(O)—, R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, (R 11 O)(R 12 O)P(O)—, or R 11 R 12 N(R 9 O)P(O)—;
R 4 is alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, T, a side-chain of a naturally or non-naturally occurring chiral amino acid,
R 6 and R 7 are independently H, alkyl, or acyl; or R 6 and R 7 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring;
R 8 is H, alkyl, heteroalkyl, or acyl;
R 9 , R 11 , and R 12 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, heteroarylheteroalkyl, or T;
R 11 and R 12 can be taken together to form a heterocyclic ring;
R 10 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, heteroarylheteroalkyl or T;
R 13 is H, methyl, ethyl, isopropyl or tert-butyl;
R 14 is independently D, F, Cl, Br, I, —CH 3 , —OCH 3 , CH 2 CH 3 , —OCH 2 CH 3 , —CCl 3 , —CF 3 , —C≡N, —OH, or —NO 2 ;
R 15 is H, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, or acyl;
R 16 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, or arylalkyl;
T is —(CH 2 ) w —(O) x —[(CH 2 CH 2 )—O] q —R 13 ;
the absolute stereochemistry at each of stereocenters *1, *2, *3 and *4 is independently R (D for an amino acid) or S (L for an amino acid);
n and m are independently 1, 2, 3, 4, 5, or 6;
p is 0, 1, 2, 3, 4, or 5;
q is an integer from 1-30 inclusive;
x is 0 or 1; and
w is 0, 1 or 2; provided that: if x is 0, then w is 0; and if w is 0, then y is 0;
“**” denotes the point of attachment of X to W; and
“***” denotes the point of attachment of W to Y.
97 . The compound of claim 96 , wherein X is —N(R 15 ).
98 . The compound of claim 96 , wherein X is
99 . The compound of claim 96 , wherein X is
100 . The compound of claim 96 , wherein X is
101 . The compound of any one of claims 96 - 101 , wherein Y is —N(R 15 )—.
102 . The compound of any one of claims 96 - 101 , wherein Y is
103 . The compound of any one of claims 96 - 101 , wherein Y is
104 . The compound of any one of claims 96 - 101 , wherein Y is
105 . The compound of any one of claims 96 - 101 , wherein W is —C(O)—.
106 . The compound of any one of claims 96 - 101 , wherein W is —C(S)—, or —C(R 16 ) 2 .
107 . The compound of any one of claims 96 - 101 , wherein W is —S(O)—, or —S(O 2 )—.
108 . The compound of any one of claims 96 - 101 , wherein W is —P(O)[Q(R 10 )]—;
109 . The compound of claim 108 , wherein Q is O.
110 . The compound of claim 108 , wherein Q is a bond.
111 . The compound of any one of claims 96 - 110 , wherein R 3 is H.
112 . The compound of any one of claims 96 - 110 , wherein R 3 is alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, heteroalkyl, or heteroaryl.
113 . The compound of any one of claims 96 - 110 , wherein R 3 is T.
114 . The compound of claim 108 , wherein R 3 is —[(CH 2 CH 2 )—O] q —R 13 .
115 . The compound of any one of claims 96 - 110 , wherein R 3 is R 9 C(O)—, R 10 OC(O)—, or (R 11 O)(R 12 O)P(O)—.
116 . The compound of any one of claims 96 - 110 , wherein R 3 is R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, or R 11 R 12 N(R 9 O)P(O)—.
117 . The compound of any one of claims 96 - 116 , wherein R 4 is alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, or arylheteroalkyl.
118 . The compound of any one of claims 96 - 116 , wherein R 4 is T.
119 . The compound of claim 118 , wherein R 4 is —(CH 2 )—(O)—[(CH 2 CH 2 )—O] q —R 13 .
120 . The compound of claim 118 , wherein R 4 is —(CH 2 ) 2 —(O)—[(CH 2 CH 2 )—O] q —R 13 .
121 . The compound of any one of claims 96 - 116 , wherein R 4 is a side-chain of a naturally or non-naturally occurring chiral amino acid.
122 . The compound of any one of claims 96 - 116 , wherein R 4 is
123 . The compound of any one of claims 96 - 116 , wherein R 4 is
124 . The compound of any one of claims 96 - 116 , wherein R 4 is
125 . The compound of claim 124 , wherein R 5 is
and each R 14 is H.
126 . The compound of any one of claims 96 - 125 , wherein R 6 is H.
127 . The compound of any one of claims 96 - 125 , wherein R 6 is alkyl or acyl.
128 . The compound of any one of claims 96 - 127 , wherein R 7 is H.
129 . The compound of any one of claims 96 - 127 , wherein R 7 is alkyl or acyl.
130 . The compound of any one of claims 96 - 125 , wherein R 6 and R 7 together with the nitrogen atom to which they are attached form a 4-6-membered heterocyclic ring.
131 . The compound of any one of claims 96 - 130 , wherein R 8 is H.
132 . The compound of any one of claims 96 - 130 , wherein R 8 is alkyl, heteroalkyl, or acyl.
133 . The compound of any one of claims 96 - 130 , wherein R 8 is H, methyl or ethyl.
134 . The compound of any one of claims 96 - 133 , wherein R 9 is H.
135 . The compound of any one of claims 96 - 133 , wherein R 9 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, or heteroarylheteroalkyl.
136 . The compound of claim 135 , wherein R 9 is C 1 -C 8 alkyl.
137 . The compound of any one of claims 96 - 133 , wherein R 9 is T.
138 . The compound of claim 137 , wherein R 9 is —[(CH 2 CH 2 )—O] q —R 13 and q is 1-20.
139 . The compound of any one of claims 96 - 138 , wherein R 10 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, or heteroarylheteroalkyl.
140 . The compound of claim 139 , wherein R 10 is C 1 -C 8 alkyl.
141 . The compound of any one of claims 96 - 138 , wherein R 10 is T.
142 . The compound of claim 140 , wherein R 10 is —[(CH 2 CH 2 )—O] q —R 13 and q is 1-20.
143 . The compound of any one of claims 96 - 142 , wherein R 11 is H.
144 . The compound of any one of claims 96 - 142 , wherein R 11 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, or heteroarylheteroalkyl.
145 . The compound of claim 144 , wherein R 11 is C 1 -C 8 alkyl.
146 . The compound of any one of claims 96 - 142 , wherein R 11 is T.
147 . The compound of claim 146 , wherein R 11 is —[(CH 2 CH 2 )—O] q —R 13 and q is 1-20.
148 . The compound of any one of claims 96 - 147 , wherein R 12 is H.
149 . The compound of any one of claims 96 - 147 , wherein R 12 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, arylheteroalkyl, or heteroarylheteroalkyl.
150 . The compound of claim 149 , wherein R 12 is C 1 -C 8 alkyl.
151 . The compound of any one of claims 96 - 147 , wherein R 12 is T.
152 . The compound of claim 151 , wherein R 12 is —[(CH 2 CH 2 )—O] q —R 13 and q is 1-20.
153 . The compound of any one of claims 96 - 152 , wherein R 13 is H.
154 . The compound of any one of claims 96 - 152 , wherein R 13 is methyl, ethyl, isopropyl, or tert-butyl.
155 . The compound of any one of claims 96 - 124 and 126 - 154 , wherein R 14 is D.
156 . The compound of any one of claims 96 - 124 and 126 - 154 , wherein R 14 is F, Cl, Br, I, —CCl 3 , or —CF 3 .
157 . The compound of any one of claims 96 - 124 and 126 - 154 , wherein R 14 is —CH 3 , —OCH 3 , CH 2 CH 3 , —OCH 2 CH 3 , —C≡N, —OH, or —NO 2 .
158 . The compound of any one of claims 96 - 157 , wherein R 15 is H.
159 . The compound of any one of claims 96 - 157 , wherein R 15 is alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, or acyl.
160 . The compound of claim 159 , wherein R 15 is methyl, ethyl, isopropyl or tert-butyl.
161 . The compound of any one of claims 96 - 160 , wherein R 16 is alkyl, alkenyl, alkynyl, or heteroalkyl.
162 . The compound of claim 160 , wherein R 16 is methyl, ethyl, isopropyl or tert-butyl.
163 . The compound of any one of claims 96 - 160 , wherein R 16 is cycloalkyl, aryl, or arylalkyl.
164 . The compound of any one of claims 96 - 163 , wherein R 17 is H.
165 . The compound of any one of claims 96 - 163 , wherein R 17 is alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylheteroalkyl, cycloalkyl, heteroalkyl, or heteroaryl.
166 . The compound of any one of claims 96 - 163 , wherein R 17 is —(CH 2 )—(O)—[(CH 2 CH 2 )—O] q —R 13 or —(CH 2 ) 2 —(O)—[(CH 2 CH 2 )—O] q —R 13 .
167 . The compound of any one of claims 96 - 163 , wherein R 17 is R 9 C(O)—, R 10 OC(O)—, or (R 11 O)(R 12 O)P(O)—.
168 . The compound of any one of claims 96 - 163 , wherein R 17 is R 11 R 12 NC(O)—, R 10 S(O)—, R 10 S(O) 2 —, R 10 OS(O)—, R 10 OS(O) 2 —, or R 11 R 12 N(R 9 O)P(O)—.
169 . The compound of any one of claims 96 - 163 , wherein R 17 is methyl or ethyl
170 . The compound of any one of claims 96 - 169 , wherein n is 1, 2, 3 or 4.
171 . The compound of any one of claims 96 - 169 , wherein n is 5, or 6.
172 . The compound of any one of claims 96 - 169 , wherein m is 1, 2, 3 or 4.
173 . The compound of any one of claims 96 - 169 , wherein m is 5, or 6.
174 . The compound of any one of claims 96 - 173 , wherein the stereochemistry at the carbon atom labeled *4 is D, the stereochemistry at the carbon atom labeled *3 is L, the stereochemistry at the carbon atom labeled *2 is L, and the stereochemistry at the carbon atom labeled *1 is L.
175 . The compound of any one of claims 96 - 173 , wherein the stereochemistry at the carbon atom labeled *4 is L, the stereochemistry at the carbon atom labeled *3 is D, the stereochemistry at the carbon atom labeled *2 is D, and the stereochemistry at the carbon atom labeled *1 is D.
176 . The compound of any one of claims 96 - 173 , wherein the stereochemistry at the carbon atom labeled *4 is D, the stereochemistry at the carbon atom labeled *3 is D, the stereochemistry at the carbon atom labeled *2 is D, and the stereochemistry at the carbon atom labeled *1 is D.
177 . The compound of any one of claims 96 - 173 , wherein the stereochemistry at the carbon atom labeled *4 is L, the stereochemistry at the carbon atom labeled *3 is L, the stereochemistry at the carbon atom labeled *2 is L, and the stereochemistry at the carbon atom labeled *1 is L.
178 . The compound of any one of claims 96 - 173 , wherein the stereochemistry at the carbon atom labeled *4 is D, the stereochemistry at the carbon atom labeled *3 is L, the stereochemistry at the carbon atom labeled *2 is D, and the stereochemistry at the carbon atom labeled *1 is L.
179 . The compound of any one of claims 96 - 173 , wherein the stereochemistry at the carbon atom labeled *4 is L, the stereochemistry at the carbon atom labeled *3 is D, the stereochemistry at the carbon atom labeled *2 is L, and the stereochemistry at the carbon atom labeled *1 is D.
180 . The compound of claim 96 , wherein the compound is
181 . The compound of claim 96 , wherein the compound is