US2017348324A1PendingUtilityA1
Derivatives of betulin
Est. expiryDec 16, 2031(~5.4 yrs left)· nominal 20-yr term from priority
A61P 31/18A61P 31/00A61P 31/12C07C 2601/14C07D 413/06A61K 31/56C07D 243/08A61K 31/4985A61K 31/40A61K 31/568C07D 213/40C07D 239/26C07D 205/04C07C 2601/02C07D 265/30A61K 31/54C07C 217/26C07D 207/09C07C 69/34A61K 31/225C07J 63/008A61K 45/06A61K 31/495C07J 53/002C07D 265/32C07C 225/14A61K 31/551A61K 31/5375A61K 31/472A61K 31/44A61K 31/397C07C 219/24C07C 211/38C07C 2603/52A61K 31/58C07D 498/14A61K 31/505C07C 233/33C07D 239/48A61K 31/222A61K 31/506C07D 217/04C07C 211/10C07C 215/08C07C 219/06C07C 211/04
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Claims
Abstract
The present invention relates to compounds characterized by having a structure according to the following Formula I: , or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound having the structure of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A is
L 1 and L 2 are independently selected from a bond or [C(R 6 R 6′ )] q ;
each instance of Q is independently selected from—CH 2 — or —C(═O)—;
W is selected from a bond or O;
R 1 is selected from the group consisting of —H, (C 1 -C 12 )alkyl, —C(O)R 5 , —CH 2 —O—(C 1 -C 6 )alkyl, 2-tetrahydro-2H-pyran, and
R 2 is selected from the group consisting of —H, (C 1 -C 12 )alkyl, —(C 1 -C 6 )alkyl-OR 4 , —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, —C(O)R 5 , —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r N + (R 4 ) 3 , wherein when W is O, R 1 and R 2 can optionally be taken together with the O and N to which they are respectively joined to form a 4 to 8 membered heterocyclyl ring, wherein the heterocyclyl ring may be optionally substituted by one to two R 11 groups;
R 3 is selected from the group consisting of hydrogen, (C 1 -C 12 )alkyl, —NR 1 R 2 , —OR 5 ,
wherein:
X is a monocyclic or bicyclic (C 6 -C 1 a)aryl, Y is selected from a monocyclic or bicyclic (C 2 -C 6 )heterocyclyl or monocyclic or bicyclic (C 2 -C 6 )heteroaryl, each having one to three heteroatoms selected from S, N or O, and Z is a monocyclic or bicyclic (C 3 -C 8 )cycloalkyl;
R 2 and R 3 can optionally be taken together with the nitrogen and L 2 to which they are respectively joined to form a 4 to 8 membered heterocyclyl ring, wherein the heterocyclyl ring may be optionally substituted by one to two R 11 groups;
R 4 is selected from the group consisting of —H and (C 1 -C 6 )alkyl;
R 5 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, —R 3 , —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r OR 7 .
R 6 and R 6′ are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, haloalkyl, —Y, —(CH 2 ) r NR 7 R 8 , —C(O)OH, and —C(O)NH 2 , wherein the R 6 and R 6′ groups can optionally be taken together with the carbon to which they are joined to form a 3 to 8 membered cycloalkyl ring, and wherein the cycloalkyl ring may be optionally substituted by one to three R 11 groups;
R 7 and R 8 are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, -Q-aryl-(R 4 ) n , —NR 14 R 15 , —C(O)CH 3 , wherein R 7 and R 8 can optionally be taken together with the nitrogen to which they are joined to form a 4 to 8 membered heterocyclyl or heteroaryl ring containing one to three heteroatoms selected from —NR 5 —, —O—, —S—, —S(O)—, or —SO 2 —, wherein the heterocyclyl or heteroaryl ring may be optionally substituted by one to three R 11 groups;
R 9 is halo;
R 10 is —N(R 16 ) 2 ;
R 11 , R 12 , and R 13 are independently selected from the group consisting of oxo, hydroxyl, halo, (C 1 -C 6 )alkoxy, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , nitro, —SO 2 R 6 , (C 1 -C 6 )alkyl, —C(O)R 10 , —R 4 YR 6 , —CO(O)R 4 , and —CO(O)R 5 , wherein any two R 11 , R 12 or R 13 groups can optionally join to form a 3 to 8 membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring, wherein the heterocyclyl or heteroaryl ring may contain one to three heteroatoms selected from —NR 5 —, —O—, —S—, —S(O)—, or —SO 2 —, and wherein the cycloalkyl, aryl, heterocyclyl or heteroaryl ring may be optionally substituted by one to three R 16 groups;
R 14 and R 15 are independently selected from the group consisting of —H, (C 1 —C— 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, —[C(R 6 ) 2 ] r —, —O[C(R 6 ) 2 ] r —, oxo, hydroxyl, halo, —C(O)R 7 , —R 10 , and —CO(O)R 2 , wherein R 14 and R 15 can optionally be taken together with the carbon to which they are joined to form a 3 to 8 membered cycloalkyl ring or 4 to 8 membered heterocyclyl ring containing one to three heteroatoms selected from —NR 5 —, —O—, —S—, —S(O)—, or —SO 2 —, wherein the cycloalkyl ring or heterocyclyl ring may be optionally substituted by one to three R 16 groups;
R 16 is independently selected from the group consisting of —H, halo, oxo, hydroxyl, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , —N(R 4 ) 2 , —(CH 2 ) r -heterocyclyl, —C(O)OH, —C(O)NH 2 , —R 5 (R 9 ) q , —OR 5 (R 9 ) q , nitro, —SO 2 R 6 , —C(O)R 10 , and —CO(O)R 4 ;
m and n in each instance are independently 0, 1, 2, 3, or 4;
p is independently 0, 1, 2, 3, or 4; and
r and q in each instance are independently 0, 1, 2, 3, or 4.
2 . The compound of claim 1 , wherein L 1 and L 2 are both [C(R 6 R 6′ )] q .
3 . The compound of claim 1 , wherein L 1 and L 2 are both —CH 2 —.
4 . The compound of claim 1 , wherein each instance of q is independently 1, 2, or 3.
5 . The compound of claim 1 , wherein q is 1.
6 . The compound of claim 1 , wherein W is O.
7 . The compound of claim 1 , wherein W is a bond.
8 . The compound of claim 1 , wherein when W is a bond, then R 1 is —H.
9 . The compound of claim 1 , wherein when W is O, then R 1 is —H.
10 . The compound of claim 1 , wherein Q m in the A group is absent and Q, in the A group is —CH 2 — and the Q in the Formula I structure is C(═O)
11 . The compound of claim 1 , wherein R 1 is —H.
12 . The compound of claim 1 , wherein R 2 is —(CH 2 ) r NR 7 R 8 .
13 . The compound of claim 1 , wherein R 2 is (dimethylamino)ethyl.
14 . The compound of claim 1 , wherein each instance of r is independently 0, 1, 2, or 3.
15 . The compound of claim 1 , wherein r is 2.
16 . The compound of claim 1 , wherein R 3 is
17 . The compound of claim 1 , wherein X is a monocyclic (C 5 -C 14 )aryl.
18 . The compound of claim 1 , wherein X is phenyl.
19 . The compound of claim 1 , wherein R 4 is —H.
20 . The compound of claim 1 , wherein each instance of m is independently 0 or 1.
21 . The compound of claim 1 , wherein m is 0.
22 . The compound of claim 1 , wherein m is 1.
23 . The compound of claim 1 , wherein n is 1.
24 . The compound of claim 1 , wherein R 6 and R 6′ are both —H.
25 . The compound of claim 1 , wherein R 7 and R 8 are both (C 1 -C 6 )alkyl.
26 . The compound of claim 1 , wherein R 7 is methyl.
27 . The compound of claim 1 , wherein R 8 is methyl.
28 . The compound of claim 1 , wherein R 7 and R 8 are both methyl.
29 . The compound of claim 1 , wherein R 11 is halo.
30 . The compound of claim 1 , wherein R 11 is selected from chloro, bromo, or fluoro.
31 . The compound of claim 1 , wherein R 11 is chloro.
32 . The compound of claim, wherein R 11 is absent.
33 . The compound of claim 1 , wherein R 14 and R 15 are both (C 1 -C 6 )alkyl.
34 . The compound of claim 1 , wherein R 14 and R 15 are both methyl.
35 . The compound of claim 1 , wherein A is
36 . The compound of claim 1 , wherein A is
37 . The compound of claim 1 , wherein A is
38 . The compound of claim 1 , wherein A is
39 . A compound having the structure of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A is
L 1 and L 2 are [C(R 6 R 6′ )] q ;
each Q is independently selected from—CH 2 — or —C(═O)—;
W is selected from a bond or O;
R 1 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, —C(O)R 4 , and
R 2 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkyl-OR 4 , —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, —C(O)R 5 , and —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r N + (R 4 ) 3 ;
R 3 is selected from the group consisting of —H, (C 1 -C 12 )alkyl, —NR 1 R 2 , —OR 5 ,
wherein:
X is a monocyclic or bicyclic (C 5 -C 14 )aryl, Y is selected from a monocyclic or bicyclic (C 2 -C 9 )heterocyclyl or monocyclic or bicyclic (C 2 -C 9 )heteroaryl, each having one to three heteroatoms selected from S, N or O, and Z is a monocyclic or bicyclic (C 3 -C 8 )cycloalkyl;
R 4 is selected from the group consisting of —H and (C 1 -C 6 )alkyl;
R 5 is selected from the group consisting of (C 1 -C 6 )alkyl, —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r OR 7 ;
R 6 and R 6′ are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, haloalkyl, —(CH 2 ) r NR 7 R 8 , —C(O)OH, and —C(O)NH 2 , wherein the R 6 and R 6′ groups can optionally be taken together with the carbon to which they are joined to form a 3 to 8 membered cycloalkyl ring, and wherein the cycloalkyl ring may be optionally substituted by one to three R 11 groups;
R 7 and R 8 are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, —NR 14 R 15 , and —C(O)CH 3 ;
R 9 is halo;
R 10 is —N(R 16 ) 2 ;
R 11 , R 12 , and R 13 are independently selected from the group consisting of oxo, hydroxyl, halo, (C 1 -C 6 )alkoxy, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , nitro, —SO 2 R 6 , (C 1 -C 6 )alkyl, —C(O)R 10 , —R 4 YR 6 , —CO(O)R 4 , and —CO(O)R 5 ;
R 14 and R 15 are independently selected from the group consisting of —H, (C 1 —C— 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, —[C(R 6 ) 2 ] r —, —O[C(R 6 ) 2 ] r —, oxo, hydroxyl, halo, —C(O)R 7 , —R 10 , and —CO(O)R 2 ;
R 16 is independently selected from the group consisting of —H, oxo, halo, hydroxyl, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , —N(R 4 ) 2 , —(CH 2 ) r -heterocyclyl, —C(O)OH, —C(O)NH 2 , —R 5 (R 9 ) q , —OR 5 (R 9 ) q , nitro, —SO 2 R 6 , —C(O)R 10 , and —CO(O)R 4 ;
m and n in each instance are independently 0, 1, 2, 3, or 4;
p is independently 0, 1, 2, 3, or 4; and
r and q in each instance are independently 0, 1, 2, 3, or 4.
40 . A compound having the structure of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A is
L 1 and L 2 are both (—CH 2 —);
Q is —C(═O)—;
W is O;
R 1 is —H;
R 2 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkyl-OR 4 , —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, —C(O)R 5 , and —(CH 2 ) r NR 7 R 8 ;
R 3 is selected from the group consisting of —H, (C 1 -C 12 )alkyl, —NR 1 R 2 , —OR 5 ,
wherein:
X is a monocyclic or bicyclic (C 5 -C 14 )aryl, Y is selected from a monocyclic or bicyclic (C 2 -C 9 )heterocyclyl or monocyclic or bicyclic (C 2 -C 9 )heteroaryl, each having one to three heteroatoms selected from S, N or O, and Z is a monocyclic or bicyclic (C 3 -C 8 )cycloalkyl;
R 4 is selected from the group consisting of —H and (C 1 -C 6 )alkyl;
R 5 is selected from the group consisting of (C 1 -C 6 )alkyl, —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r OR 7 ;
R 6 and R 6′ are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, haloalkyl, —(CH 2 ) r NR 7 R 8 , —C(O)OH, and —C(O)NH 2 ;
R 7 and R 8 are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, —NR 14 R 15 , and —C(O)CH 3 ;
R 9 is halo;
R 10 is —N(R 16 ) 2 ;
R 11 , R 12 , and R 13 are independently selected from the group consisting of oxo, hydroxyl, halo, (C 1 -C 6 )alkoxy, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , nitro, —SO 2 R 6 , (C 1 -C 6 )alkyl, —C(O)R 10 , —R 4 YR 6 , —CO(O)R 4 , and —CO(O)R 5 ;
R 14 and R 15 are independently selected from the group consisting of —H, (C 1 —C— 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, —[C(R 6 ) 2 ] r —, —O[C(R 6 ) 2 ] r —, oxo, hydroxyl, halo, —C(O)R 7 , —R 10 , and —CO(O)R 2 ;
R 16 is independently selected from the group consisting of —H, oxo, halo, hydroxyl, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , —N(R 4 ) 2 , —(CH 2 ) r -heterocyclyl, —C(O)OH, —C(O)NH 2 , —R 5 (R 9 ) q , —OR 5 (R 9 ) q , nitro, —SO 2 R 6 , —C(O)R 10 , and —CO(O)R 4 ;
m and n in each instance are independently 0, 1, or 2;
p is independently 0, 1, or 2; and
r and q in each instance are independently 0, 1, 2, or 3.
41 . A compound having the structure of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A is
L 1 and L 2 are both (—CH 2 —);
Q is —C(═O)—;
W is O;
R 1 is —H;
R 2 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, —C(O)R 5 , and —(CH 2 ) r NR 7 R 8 ;
R 3 is
wherein X is a monocyclic or bicyclic (C 5 -C 14 )aryl;
R 4 is selected from the group consisting of —H and (C 1 -C 6 )alkyl;
R 5 is selected from the group consisting of (C 1 -C 6 )alkyl, —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r OR 7 ;
R 6 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, haloalkyl, —(CH 2 ) r NR 7 R 8 , —C(O)OH, and —C(O)NH 2 ;
R 7 and R 8 are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, —NR 14 R 15 , and —C(O)CH 3 ;
R 9 is halo;
R 10 is —N(R 16 ) 2 ;
R 11 , R 12 , and R 13 are independently selected from the group consisting of oxo, hydroxyl, halo, (C 1 -C 6 )alkoxy, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , nitro, —SO 2 R 6 , (C 1 -C 6 )alkyl, —C(O)R 10 , —CO(O)R 4 , and —CO(O)R 5 ;
R 14 and R 15 are independently selected from the group consisting of —H, (C 1 —C— 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, —[C(R 6 ) 2 ] r —, —O[C(R 6 ) 2 ] r —, oxo, hydroxyl, halo, —C(O)R 7 , —R 10 , and —CO(O)R 2 ;
R 16 is independently selected from the group consisting of —H, oxo, halo, hydroxyl, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , —N(R 4 ) 2 , —(CH 2 ) r -heterocyclyl, —C(O)OH, —C(O)NH 2 , —R 5 (R 9 ) q , —OR 5 (R 9 ) q , nitro, —SO 2 R 6 , —C(O)R 10 , and —CO(O)R 4 ;
m and n in each instance are independently 0, 1, or 2;
p is independently 0, 1, or 2; and
r and q in each instance are independently 0, 1, 2, or 3.
42 . A compound having the structure of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A is
L 1 and L 2 are both (—CH 2 —);
Q is —C(═O)—;
W is O;
R 1 is —H;
R 2 is —(CH 2 ) r NR 7 R 8 ;
R 3 is
wherein X is phenyl;
R 7 and R 8 are independently selected from the group consisting of —H and methyl;
R 9 is selected from the group consisting of chloro, bromo, and fluoro;
R 11 is selected from the group consisting of chloro, bromo, and fluoro;
m is independently 0, 1, or 2; and
r is independently 1, 2, or 3.
43 . A compound having the structure of Formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
A is
L 1 and L 2 are independently selected from a bond or [C(R 6 R 6′ )] q ;
each instance of Q is independently selected from—CH 2 — or —C(═O)—;
W is selected from a bond or O;
R 1 is selected from the group consisting of —H, (C 1 -C 12 )alkyl, —C(O)R 5 , —CH 2 —O—(C 1 -C 6 )alkyl, 2-tetrahydro-2H-pyran, and
R 2 is selected from the group consisting of —H, —(C 1 -C 6 )alkyl-OR 4 , —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, —C(O)R 5 , —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r N + (R 4 ) 3 , wherein when W is O, R 1 and R 2 can optionally be taken together with the O and N to which they are respectively joined to form a 4 to 8 membered heterocyclyl ring, wherein the heterocyclyl ring may be optionally substituted by one to two R 11 groups;
R 3 is selected from the group consisting of —H, (C 1 -C 12 )alkyl, —NR 1 R 2 , —OR 5 ,
wherein:
X is a monocyclic or bicyclic (C 6 -C 1 a)aryl, Y is selected from a monocyclic or bicyclic (C 2 -C 6 )heterocyclyl or monocyclic or bicyclic (C 2 -C 6 )heteroaryl, each having one to three heteroatoms selected from S, N or O, and Z is a monocyclic or bicyclic (C 3 -C 8 )cycloalkyl;
R 2 and R 3 can optionally be taken together with the nitrogen and L 2 to which they are respectively joined to form a 4 to 8 membered heterocyclyl ring wherein the heterocyclyl ring may be optionally substituted by one to two R 11 groups;
R 4 is selected from the group consisting of —H and (C 1 -C 6 )alkyl;
R 5 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, —R 3 , —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r OR 7 .
R 6 and R 6′ are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, haloalkyl, —Y, —(CH 2 ) r NR 7 R 8 , —C(O)OH, and —C(O)NH 2 , wherein the R 6 and R 6′ groups can optionally be taken together with the carbon to which they are joined to form a 3 to 8 membered cycloalkyl ring, and wherein the cycloalkyl ring may be optionally substituted by one to three R 11 groups;
R 7 and R 8 are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, -Q-aryl-(R 4 ) n , —NR 14 R 15 , —C(O)CH 3 , wherein R 7 and R 8 can optionally be taken together with the nitrogen to which they are joined to form a 4 to 8 membered heterocyclyl or heteroaryl ring containing one to three heteroatoms selected from —NR 5 —, —O—, —S—, —S(O)—, or —SO 2 —, wherein the heterocyclyl or heteroaryl ring may be optionally substituted by one to three R 11 groups;
R 9 is halo;
R 10 is —N(R 16 ) 2 ;
R 11 , R 12 , and R 13 are independently selected from the group consisting of oxo, hydroxyl, halo, (C 1 -C 6 )alkoxy, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , nitro, —SO 2 R 6 , (C 1 -C 6 )alkyl, —C(O)R 10 , —R 4 YR 6 , —CO(O)R 4 , and —CO(O)R 5 , wherein any two R 11 , R 12 or R 13 groups can optionally join to form a 3 to 8 membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring, wherein the heterocyclyl or heteroaryl ring may contain one to three heteroatoms selected from —NR 5 —, —O—, —S—, —S(O)—, or —SO 2 —, and wherein the cycloalkyl, aryl, heterocyclyl or heteroaryl ring may be optionally substituted by one to three R 16 groups;
R 14 and R 15 are independently selected from the group consisting of —H, (C 1 —C— 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, —[C(R 6 ) 2 ] r —, —O[C(R 6 ) 2 ] r —, oxo, hydroxyl, halo, —C(O)R 7 , —R 10 , and —CO(O)R 2 , wherein R 14 and R 15 can optionally be taken together with the carbon to which they are joined to form a 3 to 8 membered cycloalkyl ring or 4 to 8 membered heterocyclyl ring containing one to three heteroatoms selected from —NR 5 —, —O—, —S—, —S(O)—, or —SO 2 —, wherein the cycloalkyl ring or heterocyclyl ring may be optionally substituted by one to three R 16 groups;
R 16 is independently selected from the group consisting of —H, halo, oxo, hydroxyl, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , —N(R 4 ) 2 , —(CH 2 ) r -heterocyclyl, —C(O)OH, —C(O)NH 2 , —R 5 (R 9 ) q , —OR 5 (R 9 ) q , nitro, —SO 2 R 6 , —C(O)R 10 , and —CO(O)R 4 ;
m and n in each instance are independently 0, 1, 2, 3, or 4;
p is independently 0, 1, 2, 3, or 4; and
r and q in each instance are independently 0, 1, 2, 3, or 4.
44 . A compound having the structure of Formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
A is
L 1 and L 2 are [C(R 6 R 6′ )] q ;
each instance of Q is independently selected from—CH 2 — or —C(═O)—;
W is selected from a bond or O;
R 1 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, —C(O)R 4 , and
R 2 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkyl-OR 4 , —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, —C(O)R 5 , —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r N + (R 4 ) 3 ;
R 3 is selected from the group consisting of —H, (C 1 -C 12 )alkyl, —NR 1 R 2 , —OR 5 ,
wherein:
X is a monocyclic or bicyclic (C 5 -C 14 )aryl, Y is selected from a monocyclic or bicyclic (C 2 -C 9 )heterocyclyl or monocyclic or bicyclic (C 2 -C 9 )heteroaryl, each having one to three heteroatoms selected from S, N or O, and Z is a monocyclic or bicyclic (C 3 -C 8 )cycloalkyl;
R 4 is selected from the group consisting of —H and (C 1 -C 6 )alkyl;
R 5 is selected from the group consisting of (C 1 -C 6 )alkyl, —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r OR 7 ;
R 6 and R 6′ are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, haloalkyl, —(CH 2 ) r NR 7 R 8 , —C(O)OH, and —C(O)NH 2 , wherein the R 6 and R 6′ groups can optionally be taken together with the carbon to which they are joined to form a 3 to 8 membered cycloalkyl ring, and wherein the cycloalkyl ring may be optionally substituted by one to three R 11 groups;
R 7 and R 8 are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, —NR 14 R 15 , and —C(O)CH 3 ;
R 9 is halo;
R 10 is —N(R 16 ) 2 ;
R 11 , R 12 , and R 13 are independently selected from the group consisting of oxo, hydroxyl, halo, (C 1 -C 6 )alkoxy, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , nitro, —SO 2 R 6 , (C 1 -C 6 )alkyl, —C(O)R 10 , —R 4 YR 6 , —CO(O)R 4 , and —CO(O)R 6 ;
R 14 and R 15 are independently selected from the group consisting of —H, (C 1 —C— 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, —[C(R 6 ) 2 ] r —, —O[C(R 6 ) 2 ] r —, oxo, hydroxyl, halo, —C(O)R 7 , —R 10 , and —CO(O)R 2 ;
R 16 is independently selected from the group consisting of —H, oxo, halo, hydroxyl, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , —N(R 4 ) 2 , —(CH 2 ) r -heterocyclyl, —C(O)OH, —C(O)NH 2 , —R 5 (R 9 ) q , —OR 5 (R 9 ) q , nitro, —SO 2 R 6 , —C(O)R 10 , and —CO(O)R 4 ;
m and n in each instance are independently 0, 1, 2, 3, or 4;
p is independently 0, 1, 2, 3, or 4; and
r and q in each instance are independently 0, 1, 2, 3, or 4.
45 . A compound having the structure of Formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
A is
L 1 and L 2 are both (—CH 2 —);
Q is —C(═O)—;
W is O;
R 1 is —H;
R 2 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, —C(O)R 5 , and —(CH 2 ) r NR 7 R 8 ;
R 3 is
wherein X is a monocyclic or bicyclic (C 5 -C 14 )aryl;
R 4 is selected from the group consisting of —H and (C 1 -C 6 )alkyl;
R 5 is selected from the group consisting of (C 1 -C 6 )alkyl, —(CH 2 ) r NR 7 R 8 , and —(CH 2 ) r OR 7 ;
R 6 is selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, haloalkyl, —(CH 2 ) r NR 7 R 8 , —C(O)OH, and —C(O)NH 2 ;
R 7 and R 8 are independently selected from the group consisting of —H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, —NR 14 R 15 , and —C(O)CH 3 ;
R 9 is halo;
R 10 is —N(R 16 ) 2 ;
R 11 , R 12 , and R 13 are independently selected from the group consisting of oxo, hydroxyl, halo, (C 1 -C 6 )alkoxy, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , nitro, —SO 2 R 6 , (C 1 -C 6 )alkyl, —C(O)R 10 , —CO(O)R 4 , and —CO(O)R 5 ;
R 14 and R 15 are independently selected from the group consisting of —H, (C 1 -—C— 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxy, —[C(R 6 ) 2 ] r —, —O[C(R 6 ) 2 ] r —, oxo, hydroxyl, halo, —C(O)R 7 , —R 10 , and —CO(O)R 2 ;
R 16 is independently selected from the group consisting of —H, oxo, halo, hydroxyl, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, —R 6 (R 9 ) q , —OR 6 (R 9 ) q , —N(R 4 ) 2 , —(CH 2 ) r -heterocycle, —C(O)OH, —C(O)NH 2 , —R 5 (R 9 ) q , —OR 5 (R 9 ) q , nitro, —SO 2 R 6 , —C(O)R 10 , and —CO(O)R 4 ;
m and n in each instance are independently 0, 1, or 2;
p is independently 0, 1, or 2; and
r and q in each instance are independently 0, 1, 2, or 3.
46 . A compound having the structure of Formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
A is
L 1 and L 2 are both (—CH 2 —);
Q is —C(═O)—;
W is O;
R 1 is —H;
R 2 is —(CH 2 ) r NR 7 R 8 ;
R 3 is
wherein X is phenyl;
R 7 and R 8 are independently selected from the group consisting of —H and methyl;
R 9 is selected from the group consisting of chloro, bromo, and fluoro;
R 11 is selected from the group consisting of chloro, bromo, and fluoro;
m is 0, 1, or 2; and
r is 1, 2, or 3.
47 . A compound having the structure:
or a pharmaceutically acceptable salt thereof.
48 . A compound having the structure:
or a pharmaceutically acceptable salt thereof.
49 . A compound having the structure:
or a pharmaceutically acceptable salt thereof.
50 . A compound having the structure:
or a pharmaceutically acceptable salt thereof.
51 . A compound or a pharmaceutically acceptable salt thereof selected from the group consisting of:
Parent Structure
Chemical Name
4-[(1R)-1- [(1R,2R,5R,10S,13R,14R,17S,19R)- 17-[(3-carboxy-3,3- dimethylpropanoyl)oxy]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2-yl)pentacyclo [11.8.0.0{circumflex over ( )}{1,10}.0{circumflex over ( )}{5,9}.0{circumflex over ( )} {14, 19}]henicos-8-en-5-yl]-2- {[(4- chlorophenyl)methyl]amino}ethoxy]- 2,2-dimethyl-4-oxobutanoic acid
4-[(1R)-1- [(1R,2R,5R,10S,13R,14R,17S,19R)- 17-[(3-carboxy-3,3- dimethylpropanoyl)oxy]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2-yl)pentacyclo [11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )} {14,19}]henicos-8-en-5-yl]-2- {[(4-chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}eth- oxy]-2,2-dimethyl-4-oxobutanoic acid
4-[(1S)-1- [(1R,2R,5R,10S,13R,14R,17S,19R)- 17-[(3-carboxy-3,3- dimethylpropanyl)oxy]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-5-yl]-2- {[(4- chlorophenyl)methyl]amino}ethoxy]- 2,2-dimethyl-4-oxobutanoic acid
4-[(1S)-1- [(1R,2R,5R,10S,13R,14R,17S,19R)- 17-[(3-carboxy-3,3- dimethylpropanyl)oxy]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-5-yl]-2- {[(4-chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}eth- oxy]-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{[(4- chlorophenyl)methyl]amino}ethyl)- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )} {14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[2-(benzylamino)ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{[(3- chlorophenyl)methyl]amino}ethyl)- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy]-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{[(3-chloro-2- fluorophenyl)methyl]amino}ethyl)- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{[1-(4- chlorophenyl)cyclopropyl]amino}eth- yl)-1,2,14,18,18-pentamethyl-7- oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{[(4- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}ethyl)- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{[1-(4- chlorophenyl)cyclopropyl][2- (dimethylamino)ethyl]amino}ethyl)- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- y)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{[(4- chlorophenyl)methyl](methyl)amino} ethyl)-1,2,14,18,18-pentamethyl- 7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{N-[(4- chlorophenyl)methyl]acetamido}eth- yl)-1,2,14,18,18-pentamethyl-7- oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(4- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2.10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(4- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(4- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-1-(acetyloxy)-2-{[(4- chlorophenyl)methyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(4- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(4- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-1-(acetyloxy)-2-{[(4- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-1-(acetyloxy)-2-{[(4- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
5- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(4- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-3,3-dimethyl-5- oxopentanoic acid
5- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(4- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-3,3-dimethyl-5- oxopentanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(2- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(2- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-1-(acetyloxy)-2-{[(4- fluorophenyl)methyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-1-(acetyloxy)-2-{[(4- fluorophenyl)methyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-1-acetoxy-2-((4- fluorobenzyl)(methyl)amino)ethyl)- 1-isopropyl-5a,5b,8,8,11a- pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(4- chlorophenyl)methyl](methyl)amino}- 1-hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((R)-1-Acetoxy-2-((4- chlorobenzyl)(methyl)amino)ethyl)- 1-isopropyl-5a,5b,8,8,11a- pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(4- chlorophenyl)methyl](methyl)amino}- 1-hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-1-Acetoxy-2-(N- (4-chlorobenzyl)acetamido)ethyl)- 1-isopropyl-5a,5b,8,8,11a- pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{N-[(4- chlorophenyl)methyl]acetamido}- 1-hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-2-(N-(4- Chlorobenzyl)acetamido)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((R)-2-(N-(4- Chlorobenzyl)acetamido)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-2-(N-(2- Chlorobenzyl)acetamido)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-1-(acetyloxy)-2-{[(2- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(3- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(3- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(3- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(3- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-1-(acetyloxy)-2-{[(3- chlorophenyl)methyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-1-(acetyloxy)-2-{[(3- chlorophenyl)methyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14.19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-1-acetoxy-2-((3- chlorobenzyl)(2- (dimethylamino)ethyl)amino)ethyl)- 1-isopropyl-5a,5b,8,8,11a- pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-osobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((R)-1-acetoxy-2-((3- chlorobenzyl)(2- (dimethylamino)ethyl)amino)ethyl)- 1-isopropyl-5a,5b,8,8,11a- pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((R)-2-((3- chlorobenzyl)(ethyl)amino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-2-((3- Chlorobenzyl)(2- (dimethylamino)ethyl)amino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR, 11bR,13aS)-3a-((R)-2-((3- Chlorobenzyl)(2- (dimethylamino)ethyl)amino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2- oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11, 11a,11b,12,13,13a- octadecahydro-2H- cyclopenta[a]chrysen-9-yl)oxy)- 2,2-dimethyl-4-oxobutanoic acid.
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{N-[(3- chlorophenyl)methyl]acetamido)- 1-hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{N-[(3- chlorophenyl)methyl]acetamido}- 1-hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((R)-1-acetoxy-2-((2- chlorobenzyl)(2- (dimethylamino)ethyl)amino)ethyl)- 1-isopropyl-5a,5b,8,8,11a- pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((R)-2-((2- chlorobenzyl)(ethyl)amino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(2- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(2- chlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-1-(acetyloxy)-2- (benzylamino)ethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-1-(acetyloxy)2- (benzylamino)ethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((R)-2-((3-Chloro-2- fluorobenzyl)amino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cylcopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-2-((3-chloro-2- fluorobenzyl)amino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid.
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(3-chloro-2- fluorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(3-chloro-2- fluorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-1-hydroxy-2-[(propan- 2-yl)amino]ethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-(cyclohexylamino)-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5S,10S,13R,14R,17S,19R)- 5-[1-hydroxy-2-(4- methylpiperazin-1-yl)ethyl]- 1,2,14,18,18-pentamethyl-8- (propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{[(4- chlorophenyl)methyl]amino}ethyl)- 1,2,14,18,18-pentamethyl-8- (propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5S,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(4- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5S,10S,13R,14R,17S,19R)- 5-[(1S)-2- [(cyclohexylmethyl)amino]-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-(cyclohexylamino)-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-1-hydroxy-2-(1,2,3,4- tetrahydroisoquinolin-2-yl)ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-1-hydroxy-2-(1,2,3,4- tetrahydroisoquinolin-2-yl)ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,10S,13R,14R,17S,19R)- 5-[(5S)-3-[1-(5-chloropyrimidin-2- yl)cyclopropyl]-2-oxo-1,3- oxazolidin-5-yl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,10S,13R,14R,17S,19R)- 5-[(5R)-3-[1-(5-chloropyrimidin-2- yl)cyclopropyl]-2-oxo-1,3- oxazolidin-5-yl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
5- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(4- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-3,3-dimethyl-5- oxopentanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((R)-2-(3,4- dihydroisoquinolin-2(1H)-yl)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-2-(3,4- dihydroisoquinolin-2(1H)-yl)-1- hydorxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid.
4- (((3aS,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((R)-1-hydroxy-2-(4- methylpiperazin-1-yl)ethyl)-1- isopropyl-5a,5b,8,8,11a- pentamethyl- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid.
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-(2-((4- chlorobenzyl)amino)ethyl)-1- isopropyl-5a,5b,8,8,11a- pentamethyl- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid.
4- (((3aS,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-2- ((cyclohexylmethyl)amino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid.
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-2- (cyclohexylamino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-2-(benzyl(2- (dimethylamino)ethyl)amino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-1-(acetyloxy)-2-{[2- (dimethylamino)ethyl][(4- fluorophenyl)methyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-1-(acetyloxy)-2-{[2- (dimethylamino)ethyl][(4- fluorophenyl)methyl]amino}ethyl]- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
5- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(4- chlorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-3,3-dimethyl-5- oxopentanoic acid
5- (((3aR,5aR,5bR,7aR,9S,11aR,11bR, 13aS)-3a-((S)-2-((4- chlorobenzyl)amino)-1- hydroxyethyl)-1-isopropyl- 5a,5b,8,8,11a-pentamethyl-2-oxo- 3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a, 11b,12,13,13a-octadecahydro- 2H-cyclopenta[a]chrysen-9- yl)oxy)-3,3-dimethyl-5- oxopentanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(2,4- dichlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{benzyl[2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[2- (dimethylamino)ethyl][(4- fluorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(4- fluorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[2- (dimethylamino)ethyl][(4- fluorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1S)-2-{[(4- fluorophenyl)methyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-{[(2,4- dichlorophenyl)methyl][2- (dimethylamino)ethyl]amino}-1- hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-[(1R)-2-[1-(4-chlorophenyl)- N-[2- (dimethylamino)ethyl]formamido]- 1-hydroxyethyl]-1,2,14,18,18- pentamethyl-7-oxo-8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 5-(2-{[(2- chlorophenyl)methyl]amino}ethyl)- 1,2,14,18,18-pentamethyl-7-oxo- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}-2,2-dimethyl-4-oxobutanoic acid
2,2-dimethyl-4-oxo-4- {[(1R,2R,5R,10S,13R,14R,17S,19R)- 1,2,14,18,18-pentamethyl-7- oxo-5-[2-(phenylformamido)ethyl]- 8-(propan-2- yl)pentacyclo[11.8.0.0{circumflex over ( )}{2,10}.0{circumflex over ( )}{5, 9}.0{circumflex over ( )}{14,19}]henicos-8-en-17- yl]oxy}butanoic acid
52 . The compound of claims 1 - 51 , wherein the pharmaceutically acceptable salt is a base salt.
53 . The compound of claim 52 , wherein the pharmaceutically acceptable salt is a Lysine salt.
54 . A compound having the structure:
55 . A compound having the structure:
56 . A compound having the structure:
57 . A compound having the structure:
58 . A pharmaceutical composition comprising a compound of any of claims 1 - 57 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
59 . The composition of claim 58 , wherein the compound is present in an amorphous form.
60 . The composition of claim 58 , wherein the composition is in a tablet form.
61 . The composition of claim 58 , wherein the compound is present as a spray dried dispersion.
62 . A method of treating an HIV infection in a subject comprising administering to the subject a compound of any of claims 1 - 57 , or a pharmaceutically acceptable salt thereof.
63 . A method of treating an HIV infection in a subject comprising administering to the subject a pharmaceutical composition according to claim 58 .
64 . A method of preventing an HIV infection in a subject at risk for developing an HIV infection, comprising administering to the subject a compound of any of claims 1 - 57 , or a pharmaceutically acceptable salt thereof.
65 . A method of preventing an HIV infection in a subject at risk for developing an HIV infection, comprising administering to the subject a pharmaceutical composition according to claim 58 .
66 . The method of claims 62 - 65 , further comprising administration of one or more additional agents active against HIV.
67 . The method of claim 66 , wherein said one or more additional agents active against HIV is selected from the group consisting of zidovudine, didanosine, lamivudine, zalcitabine, abacavir, stavudine, adefovir, adefovir dipivoxil, fozivudine, todoxil, emtricitabine, alovudine, amdoxovir, elvucitabine, nevirapine, delavirdine, efavirenz, loviride, immunocal, oltipraz, capravirine, lersivirine, GSK2248761, TMC-278, TMC-125, etravirine, saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, fosamprenavir, brecanavir, darunavir, atazanavir, tipranavir, palinavir, lasinavir, enfuvirtide, T-20, T-1249, PRO-542, PRO-140, TNX-355, BMS-806, BMS-663068 and BMS-626529, 5-Helix, raltegravir, elvitegravir, GSK1349572, GSK1265744, vicriviroc (Sch-C), Sch-D, TAK779, maraviroc, TAK449, didanosine, tenofovir, lopinavir, and darunavir.
68 . The use of a compound or salt as defined in any of claims 1 - 57 in the manufacture of a medicament for use in the treatment of an HIV infection in a human.
69 . A process for preparing a compound of Formula (I) having the structure:
comprising the steps of:
(1) saponifying a compound having the structure:
in the presence of a first metal catalyst, in order to provide a compound having the structure:
(2) reacting the compound product of Step (1), with a compound having the structure:
in the presence of an acid chloride and a tertiary amine in order to provide a compound having the structure:
(3) reacting nitromethane with the compound product of Step (2) in the presence of a chiral ligand, an optional base, and a second metal catalyst in order to provide a compound having the structure:
(4) reducing the compound product of Step (3), in the presence of a third metal catalyst and hydrogen gas in order to provide a compound having the structure:
(5) reacting p-chlorobenzaldehyde with the compound product of Step (4), in the presence of a metal hydride, to provide a compound having the structure:
(6) acidifying the compound product of Step (5), in the presence of an acid in order to provide the compound having the structure:
(7) reacting the compound product of Step (6) with a compound having the structure according to Formula III:
wherein A 1 is either optionally absent or is selected from the group consisting —H, methyl, and ethyl; and A 2 is selected from the group consisting of —H, methoxy, ethoxy, hydroxyl, and —SO 3 − Na + ; while in the presence of a metal hydride in order to provide the compound having the structure:
70 . The process according to claim 69 , wherein one or more of Steps (1)-(7) are conducted in the presence of a solvent.
71 . The process according to claim 69 , wherein one or more of Steps (1)-(7) are conducted in the presence of an organic solvent.
72 . The process according to claim 69 , wherein one or more of Steps (1)-(7) are conducted in the presence of a solvent that is selected from the group consisting of water, dichloromethyl, methanol, tetrahydrofuran, tetrahydrofuran acetate, ethanol, ethyl acetate, heptane, isopropanol, tert-butanol, toluene, acetonitrile, and tert-butyl methyl ether.
73 . The process according to claim 69 , wherein the first metal catalyst of Step (1) is a metal halide.
74 . The process according to claim 69 , wherein the first metal catalyst of Step (1) is zirconium tetrachloride.
75 . The process according to claim 69 , wherein the acid chloride of Step (2) is selected from the group consisting of benzoyl chloride and methoxybenzoyl chloride.
76 . The process according to claim 69 , wherein the acid chloride of Step (2) is methoxybenzoyl chloride.
77 . The process according to claim 69 , wherein the tertiary amine of Step (2) is a tertiary amine coupling agent.
78 . The process according to claim 69 , wherein the tertiary amine of Step (2) is selected from the group consisting of triethylamine, N,N-diisopropylethylamine, and 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride.
79 . The process according to claim 69 , wherein the tertiary amine of Step (2) is 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride.
80 . The process according to claim 69 , wherein the tertiary amine of Step (2) is triethylamine.
81 . The process according to claim 69 , wherein the second metal catalyst of Step (3) is a compound comprising a metal selected from the group consisting of Zn, Co, Cu, Mg, and Cr.
82 . The process according to claim 69 , wherein the second metal catalyst of Step (3) is a compound comprising a metal selected from the group consisting of Cu(I) and Cu(II).
83 . The process according to claim 69 , wherein the second metal catalyst of Step (3) is a compound comprising Cu(I).
84 . The process according to claim 69 , wherein the second metal catalyst of Step (3) is selected from the group consisting of Copper(I) acetate and Cu(II) acetate.
85 . The process according to claim 69 , wherein the second metal catalyst of Step (3) is Copper(I) acetate.
86 . The process according to claim 69 , wherein the second metal catalyst of Step (3) is Copper(II) acetate.
87 . The process according to claim 69 , wherein the optional base of Step (3) is selected from the group consisting of alkali metal hydroxides, alkoxides, carbonates, fluoride anions, and nonionic organic amine bases.
88 . The process according to claim 69 , wherein the optional base of Step (3) is i Pr 2 Net.
89 . The process according to claim 69 , wherein the chiral ligand of Step (3) is a derivative of S-Camphor.
90 . The process according to claim 69 , wherein the chiral ligand of Step (3) is a compound having the structure:
91 . The process according to claim 69 , wherein the third metal catalyst of Step (4) is selected from the group consisting of Raney Nickel, nickel, nickel chloride, aluminum, palladium, copper, zinc, chromium, iridium, rhodium, platinum, and combinations thereof.
92 . The process according to claim 69 , wherein the third metal catalyst of Step (4) is Raney Nickel.
93 . The process according to claim 69 , wherein the hydrogen of Step (4) is hydrogen gas.
94 . The process according to claim 69 , wherein the metal hydride of Step (5) is a borohydride.
95 . The process according to claim 69 , wherein the metal hydride of Step (5) is selected from the group consisting of NaBH 4 and NaBH(OAc) 3 .
96 . The process according to claim 69 , wherein the metal hydride of Step (5) is NaBH 4 .
97 . The process according to claim 69 , wherein the metal hydride of Step (5) is NaBH(OAc) 3 .
98 . The process according to claim 69 , wherein the acid of Step (6) is selected from the group consisting of trifluoroacetic acid, HCl, and trichloroacetic acid,
99 . The process according to claim 69 , wherein the acid of Step (6) is trifluoroacetic acid.
100 . The process according to claim 69 , wherein the A 2 of Step (7) is —SO 3 Na.
101 . The process according to claim 69 , wherein the A 2 of Step (7) is —H.
102 . The process according to claim 69 , wherein the A 1 of Step (7) is absent.
103 . The process according to claim 69 , wherein the A 1 of Step (7) is —H.
104 . The process according to claim 69 , wherein the compound of Formula III of Step (7) has the following structure:
105 . The process according to claim 69 , wherein the compound of Formula III of Step (7) has the following structure:
106 . The process according to claim 69 , wherein the compound of Formula III of Step (7) has the following structure:
107 . The process according to claim 69 , wherein the compound of Formula III of Step (7) has the following structure:
108 . The process according to claim 69 , wherein the metal hydride of Step (7) is a borohydride.
109 . The process according to claim 69 , wherein the metal hydride of Step (7) is NaBH 3 CN.
110 . A process for preparing a compound having the structure:
comprising the steps of:
(1) saponifying a compound having the structure:
in the presence of a first metal catalyst, in order to provide a compound having the structure:
(2) reacting the compound product of Step (1), with a compound having the structure:
in the presence of an acid chloride and a tertiary amine in order to provide a compound having the structure:
(3) reacting nitromethane with the compound product of Step (2) in the presence of a chiral ligand and a base and a second metal catalyst in order to provide a compound having the structure:
(4) reducing the compound product of Step (3), in the presence of a third metal catalyst and hydrogen gas in order to provide a compound having the structure:
(5) reacting p-chlorobenzaldehyde with the compound product of Step (4), in the presence of a metal hydride and a tertiary amine, to provide a compound having the structure:
(6) reacting the compound product of Step (5) with a compound having the structure according to Formula III:
wherein A 1 is either optionally absent or is selected from the group consisting —H, methyl, and ethyl; and A 2 is selected from the group consisting of —H, methoxy, ethoxy, hydroxyl, and —SO 3 − Na + ; while in the presence of a metal hydride in order to provide the compound having the structure:
(7) acidifying the compound product of Step (6), in the presence of an acid in order to provide the compound having the structure:
111 . The process according to claim 110 , wherein one or more of Steps (1)-(7) are conducted in the presence of a solvent.
112 . The process according to claim 110 , wherein one or more of Steps (1)-(7) are conducted in the presence of an organic solvent.
113 . The process according to claim 110 , wherein one or more of Steps (1)-(7) are conducted in the presence of a solvent that is selected from the group consisting of water, dichloromethyl, methanol, tetrahydrofuran, tetrahydrofuran acetate, ethanol, ethyl acetate, heptane, isopropanol, tert-butanol, toluene, acetonitrile, and tert-butyl methyl ether.
114 . The process according to claim 110 , wherein the base of Step (3) is selected from the group consisting of alkali metal hydroxides, alkoxides, carbonates, fluoride anions, and nonionic organic amine bases.
115 . The process according to claim 110 , wherein the base of Step (3) is i Pr 2 Net.
116 . The process according to claim 110 , wherein the tertiary amine of Step (5) is selected from the group consisting of triethylamine, N,N-diisopropylethylamine, and 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride.
117 . The process according to claim 110 , wherein the tertiary amine of Step (5) is triethylamine.
118 . The process according to claim 110 , wherein the metal hydride of Step (5) is a borohydride.
119 . The process according to claim 110 , wherein the metal hydride of Step (5) is selected from the group consisting of NaBH 4 and NaBH(OAc) 3 .
120 . The process according to claim 110 , wherein the metal hydride of Step (5) is NaBH 4 .
121 . The process according to claim 110 , wherein the tertiary amine of Step (6) is triethylamine.
122 . A process for preparing a compound having the structure:
comprising the steps of:
(1) reacting a compound having the structure:
with a compound having the structure according to Formula III:
wherein A 1 is either optionally absent or is selected from the group consisting —H, methyl, and ethyl; and A 2 is selected from the group consisting of —H, methoxy, ethoxy, hydroxyl, and —SO 3 − Na + ; while in the presence of a metal hydride in order to provide the compound having the structure:
123 . A process for preparing a compound having the structure:
comprising the steps of:
(1) acidifying a compound having the structure:
in the presence of an acid in order to provide the compound having the structure:
124 . A process for preparing a compound having the structure:
comprising the steps of:
(1) reacting p-chlorobenzaldehyde with a compound having the structure:
in the presence of a metal hydride to provide the compound having the structure:
125 . A process for preparing a compound having the structure:
comprising the steps of:
(1) reducing a compound having the structure:
in the presence of a metal catalyst and hydrogen gas in order to provide the compound having the structure:
126 . A process for preparing a compound having the structure:
comprising the steps of:
(1) reacting nitromethane with a compound having the structure:
in the presence of a chiral ligand and a metal catalyst in order to provide a compound having the structure:
127 . A process for preparing a compound having the structure:
comprising the steps of:
(1) reacting a compound having the structure:
with a compound having the structure:
in the presence of an acid chloride and a tertiary amine in order to provide the computer having the structure:
128 . A process for preparing a compound having the structure:
comprising the steps of:
(1) saponifying a compound having the structure:
in the presence of a metal catalyst, in order to provide the compound having the structure:
129 . The use of a compound or salt as defined in any of claims 1 - 57 in the manufacture of a medicament for use in therapy.
130 . The method according to claims 62 - 67 , wherein the subject is a human.Join the waitlist — get patent alerts
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