Antifungal agents
View Patent ↗Novel derivatives of enfumafungin are disclosed herein, along with their, pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antifungal agents and/or inhibitors of (1,3)-β-D-glucan synthase. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating and/or preventing fungal infections and associated diseases and conditions.
1. A compound of Formula (I)
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
X is selected from the group consisting of O and H,H;
R 1 is selected from the group consisting of:
a) OH,
b) O—(C 1 -C 12 )alkyl,
c) O—(C 3 -C 8 )cycloalkyl,
d) O-heterocyclyl,
e) OC(O)H,
f) OC(O)—(C 1 -C 12 )alkyl,
g) OC(O)—(C 3 -C 8 )cycloalkyl, and
h) OC(O)-(heterocyclyl),
where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S;
R 2 is selected from the group consisting of:
a) (C 1 -C 12 )alkyl, and
b) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S, and
said R 2 is substituted by 0 to 4 R 4 groups;
R 3 is selected from the group consisting of:
a) CH 2 OH,
b) CH 2 OC(O)(C 1 -C 12 alkyl),
c) COOH,
d) COO(C 1 -C 12 )alkyl, and
e) COO(CH 2 ) 0-6 phenyl;
each R 4 is independently selected from the group consisting of:
a) (C 1 -C 12 )alkyl,
b) (C 3 -C 8 )cycloalkyl,
c) OH,
d) NR 5 2 ,
e) ONR 5 2 ,
f) O(C 1 -C 12 )alkyl,
g) C(O)R 6 ,
h) S(O) 2 R 6 , and
i)
said R 4 is substituted by 0 to 4 R 7 groups;
each R 5 is independently selected from the group consisting of:
a) H,
b) (CH 2 ) 0-12 R 6 ,
c) C(O)R 6 ,
d) S(O) 2 R 6 , and
e)
said R 5 is substituted by 0 to 13 R 7 groups;
each R 6 is independently selected from the group consisting of:
a) H,
b) OH,
c) (C 1 -C 12 )alkyl,
d) O—(C 1 -C 12 )alkyl,
e) (C 3 -C 12 )cycloalkyl,
f) (CH 2 ) 0-6 -phenyl,
g) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
h) C(O)R 8 ,
i) NR 8 2 ,
j) halogen, and
said R 6 is substituted by 0 to 13 R 7 groups;
each R 7 is independently selected from the group consisting of:
a) OH,
b) (C 1 -C 12 )alkyl,
c) O—(C 1 -C 12 )alkyl,
d) S—(C 1 -C 12 )alkyl,
e) (CH 2 ) 0-6 -phenyl,
f) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
g) C(O)R 8 ,
h) OC(O)R 8 ,
i) NR 8 2 ,
j) halogen, and
said R 7 is substituted by 0 to 13 R 9 groups;
each R 8 is independently selected from the group consisting of:
a) H,
b) (C 1 -C 12 )alkyl,
c) O—(C 1 -C 12 )alkyl,
d) (C 3 -C 12 )cycloalkyl,
e) (CH 2 ) 0-6 -phenyl,
f) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
g) C(O)R 11 , and
said R 8 is substituted by 0 to 13 R 9 groups;
each R 9 is independently selected from the group consisting of:
a) OH,
b) (C 1 -C 12 )alkyl,
c) O—(C 1 -C 12 )alkyl,
d) (C 3 -C 12 )cycloalkyl,
e) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
f) C(O)R 11 ,
g) NR 11 2 ,
h) halogen, and
said R 9 is substituted by 0 to 13 R 10 groups;
each R 10 is independently selected from the group consisting of:
a) halogen,
b) ═O, and
c) C(O)R 11 ; and
R 11 is selected from the group consisting of:
a) H, and
b) (C 1 -C 12 )alkyl.
2. The compound according to claim 1 , wherein the compound has structural Formula (Ia):
3. The compound according to claim 1 , wherein X is O.
4. The compound according to claim 1 , wherein R 1 is selected from the group consisting of OC(O)H and OC(O)—(C 1 -C 12 )alkyl.
5. The compound according to claim 1 , wherein
R 2 is selected from the group consisting of (C 1 -C 12 )alkyl that are substituted by 1 to 4 R 4 groups; and
said R 4 groups are independently selected from the group consisting of OH, NR 5 2 , O(C 1 -C 12 )alkyl, C(O)R 6 and S(O) 2 R 6 .
6. The compound according to claim 5 , wherein
said R 4 groups are independently selected from the group consisting of NR 5 2 , C(O)R 6 and S(O) 2 R 6 ;
each R 5 is independently selected from the group consisting of H and (CH 2 ) 0-12 R 6 ;
R 6 is selected from the group consisting of H, OH and (C 1 -C 12 )alkyl; and
said R 6 is substituted by 0 to 2 NH 2 groups.
7. The compound according to claim 5 , wherein
said R 2 is substituted by NH 2 and NHR 5 ;
R 5 is selected from the group consisting of H and (CH 2 ) 0-12 R 6 ; and
R 6 is selected from the group consisting of (C 1 -C 12 )alkyl, (C 3 -C 12 )cycloalkyl, (CH 2 ) 0-6 phenyl, and heterocyclyl.
8. The compound according to claim 7 , wherein
said R 6 is substituted by 0 to 4 R 7 ; and
each R 7 is independently selected from halogen and O(C 1 -C 12 )alkyl groups.
9. The compound according to claim 1 , wherein R 2 is selected from the group consisting of heterocyclyl, where said heterocyclyl group is a 5- to 6-membered ring containing from 1 to 4 heteroatoms independently selected from N, O and S.
10. The compound according to claim 9 , wherein
said R 2 is substituted by 1 to 4 R 4 groups; and
said R 4 groups are independently selected from the group consisting of OH, NR 5 2 , O(C 1 -C 12 )alkyl, C(O)R 6 and S(O) 2 R 6 .
11. The compound according to claim 10 , wherein
said R 4 groups are independently selected from the group consisting of NR 5 2 , C(O)R 6 and S(O) 2 R 6 ;
each R 5 is independently selected from the group consisting of H and (CH 2 ) 0-12 R 6 ;
R 6 is selected from the group consisting of H, OH and (C 1 -C 12 )alkyl; and
said R 6 is substituted by 0 to 2 NH 2 groups.
12. The compound according to claim 1 , wherein the compound is selected from the group consisting of
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-3-methyl-butyryloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl -1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-4-carbamoyl-butyryloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-pentanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2,6-diamino-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-4-hydroxy-butyryloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2,5-diamino-pentanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-butyryloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-3-carboxypropionyoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-piperidinylcarboxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-pyrrolidinylcarboxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(3-amino -propionyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(3-amino-butyryloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(3-amino-propionyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-5-formylamino-pentanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(4-amino-pyrrolidine-2-carboxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-guanidino-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-acetylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-(2-methylamino-acetylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(4-hydroxy-pyrrolidine-2-carboxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-3-(2-amino-ethoxy)-propionyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-3-(2-amino-ethanesulfonyl)-propionyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-3-(2-amino-ethylamino)-propionyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-(2-amino-ethylamino)-acetoxy)-8-[(1 R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl -1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(4-amino-5-hydroxy-pentanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-(N-hydroxycarbamimidoyl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-(N-(2,6-diaminohexanoyloxy)carbamimidoyl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3,5-bis-trifluoromethyl-benzoylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-bromo-benzoylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(2,2,3,3,4,4,4-heptafluoro-butyrylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-6-(2-bromo-propionylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(2-methoxy-acetylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-[(tetrahydro-furan-2-carbonyl)-amino]-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-methoxy-benzoylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-fluoro-benzoylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-phenylacetylamino-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(cyclobutanecarbonyl-amino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3,5-dimethoxy-benzoylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(2-oxo-propionylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-chloro-benzoylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-propionylamino-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(4-chloro-benzoylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(6-(2-acetoxy-2-methyl-propionylamino)-2-amino-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(6-acetylamino-2-amino-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(2,2,2-trifluoro-acetylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-[3-(4-fluoro-phenyl)-ureido]-hexanoyloxy hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-[3-(4-trifluoromethylphenyl)-ureido]-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-isopropyl-ureido)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-[3-(4-methoxyphenyl)-ureido]-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-cyclopentyl-ureido)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-[3-(1-methoxycarbonyl-ethyl)-ureido]-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-[3-(2-bromo-ethyl)-ureido]-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-[3-(2-chloro-ethyl)-ureido]-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-hexylureido)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-phenyl-ureido)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4 a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-[3-(4-methoxycarbonylphenyl)-ureido]-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-ethoxycarbonylmethy-ureido)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(4-tert-butylbenzenesulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(4-trifluoromethylbenzenesulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(4-fluorobenzenesulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(4-bromobenzenesulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(4-methoxybenzenesulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3,5-dimethylisoxazole-4-sulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-methanesulfonylamino-hexanoyloxy)-8-[(1 R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-ethanesulfonylamino-hexanoyloxy)-8-[(1 R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-propanesulfonylamino-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-chloropropane-1-sulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3,5-bis-trifluoromethylbenzenesulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-trifluoromethylbenzenesulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(6-(4-acetylamino-benzenesulfonylamino)-2-amino-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a -tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S, 2R, 3R, 4aR, 6aS, 7R, 8R, 10aR, 10bR, 12aR)-3-(acetyloxy)-2-(2-amino-6-(3-chloro-4-fluorobenzenesulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-amino-6-(toluene-2-sulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-amino-6-(3,4-dimethoxy-benzenesulfonylamino)-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a -(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2,2-dimethyl-propylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[(tetrahydro-furan-2-ylmethyl)-amino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[2-(4-fluoro-phenyl)-1-methyl-ethylamino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(tetrahydro-pyran-4-ylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-isopropylaminoacetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-methyl-tetrahydro-furan-3-ylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(1-methyl-3-methylsulfanyl-propylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(4-diethylamino-1-methyl-butylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[(1-Methyl-pyrrolidin-2-ylmethyl)-amino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(1-methyl-piperidin-4-ylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-methoxy-1-methyl-ethylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-methyl-cyclopentylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-guanidino-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(cyclopropylmethyl-propyl-amino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[bis-(2-hydroxy-ethyl)-amino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[4-(4-fluoro-2-methoxyphenyl)-piperidin-1-yl]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-piperidin-1-ylethylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(3-imidazol-1-ylpropylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(cyclohexyl-methylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-pyrrolidin-1-yl-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a tetramethyl1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(3-hydroxy-pyrrolidin-1-yl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(4-methyl-piperazin-1-yl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-morpholin-4-yl-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-dimethylamino-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[(2,2-dimethoxyethyl)-methyl-amino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(ethyl-methyl-amino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[(2-diethylamino-ethyl)-methylamino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(4-ethyl-piperazin-1-yl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-pyrrolidin-1-yl-ethylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-morpholin-4-yl-ethylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(1-ethoxycarbonylpiperidin-4-yl)-amino-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-methoxy-1-methyl-ethylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-methylamino-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-dimethylamino-ethylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(3-isopropoxy-propylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(1,2,2,6,6-pentamethyl-piperidin-4-ylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[(piperidin-4-ylmethyl)-amino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[3-(2-methyl-piperidin-1-yl)-propylamino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(3-methylamino-propylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(3-dimethylamino-propylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(3-pyrrolidin-1-yl-propylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[(3-dimethylaminopropyl)-methyl-amino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[bis-(3-dimethylaminopropyl)-amino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(4-pyrrolidin-1-yl-piperidin-1-yl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(3-acetylamino-pyrrolidin-1-yl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(1-methyl-pyrrolidin-3-ylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(3-dimethylamino-pyrrolidin-1-yl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(4-isopropyl-piperazin-1-yl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(3-diethylamino-pyrrolidin-1-yl)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[methyl-(1-methylpiperidin-4-yl)-amino]-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-[1,4′]Bipiperidinyl-1′-yl-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a -tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-aminoacetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-6-oxo-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(pyrrolidene-2-carbonyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-6-oxo-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2,5-diamino-pentanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-6-oxo-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-amino-acetylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-6-oxo-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-(2-methylamino-acetylamino)-acetoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-6-oxo-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2,6-diamino-hexanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-6-oxo-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-((4-aminopyrrolidine)-2-carbonyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-6-oxo-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-(acetyloxy)-2-(2-amino-5-guanidino-pentanoyloxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-6-oxo-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-2-(2,6-diamino-hexanoyloxy)-3-(methoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid;
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-2-(2,6-diamino-hexanoyloxy)-3-(ethoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid; and
(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-2-(2,6-diamino-hexanoyloxy)-3-((2-methyl)ethoxy)-8-[(1R)-1,2-dimethylpropyl]-1,6a,8,10a-tetramethyl-1,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-2H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid.
13. The compound according to claim 1 , wherein
R 1 is selected from the group consisting of:
a) O—(C 1 -C 12 )alkyl,
b) OC(O)H, and
c) OC(O)—(C 1 -C 12 )alkyl;
R 2 is selected from the group consisting of:
a) (C 1 -C 12 )alkyl, and
b) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S, and
said R 2 is substituted by 0 to 4 R 4 groups;
R 3 is COOH;
each R 4 is independently selected from the group consisting of:
a) OH,
b) NR 5 2 ,
c) O(C 1 -C 12 )alkyl,
d) C(O)R 6 , and
e) S(O) 2 R 6 , and
said R 4 is substituted by 0 to 4 R 7 groups;
each R 5 is independently selected from the group consisting of:
a) H, and
b) (CH 2 ) 0-12 R 6 , and
said R 5 is substituted by 0 to 13 R 7 groups;
each R 6 is independently selected from the group consisting of:
a) H,
b) (C 1 -C 12 )alkyl,
c) (C 3 -C 12 )cycloalkyl,
d) (CH 2 ) 0-6 -phenyl,
e) heterocyclyl,
f) halogen, and
said R 6 is substituted by 0 to 13 R 7 groups; and
each R 7 is independently selected from the group consisting of:
a) O—(C 1 -C 12 )alkyl, and
b) halogen, and
said R 7 is unsubstituted.
14. A composition comprising a compound and a carrier, adjuvant or vehicle, wherein said compound comprises a compound of Formula (I)
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
X is selected from the group consisting of O and H,H;
R 1 is selected from the group consisting of:
a) OH,
b) O—(C 1 -C 12 )alkyl,
c) O—(C 3 -C 8 )cycloalkyl,
d) O-heterocyclyl,
e) OC(O)H,
f) OC(O)—(C 1 -C 12 )alkyl,
g) OC(O)—((C 3 -C 8 )cycloalkyl, and
h) OC(O)-(heterocyclyl),
where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S;
R 2 is selected from the group consisting of:
a) (C 1 -C 12 )alkyl, and
b) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S, and
said R 2 is substituted by 0 to 4 R 4 groups;
R 3 is selected from the group consisting of:
a) CH 2 OH,
b) CH 2 OC(O)(C 1 -C 12 alkyl),
c) COOH,
d) COO(C 1 -C 12 )alkyl, and
e) COO(CH 2 ) 0-6 phenyl;
each R 4 is independently selected from the group consisting of:
a) (C 1 -C 12 )alkyl,
b) (C 3 -C 8 )cycloalkyl,
c) OH,
d) NR 5 2 ,
e) ONR 5 2 ,
f) O(C 1 -C 2 )alkyl,
g) C(O)R 6 ,
h) S(O) 2 R 6 , and
i)
said R 4 is substituted by 0 to 4 R 7 groups;
each R 5 is independently selected from the group consisting of:
a) H,
b) (CH 2 ) 0-12 R 6 ,
c) C(O)R 6 ,
d) S(O) 2 R 6 , and
e)
said R 5 is substituted by 0 to 13 R 7 groups;
each R 6 is independently selected from the group consisting of:
a) H,
b) OH,
c) (C 1 -C 12 )alkyl,
d) O—(C 1 -C 12 )alkyl,
e) (C 3 -C 12 )cycloalkyl,
f) (CH 2 ) 0-6 -phenyl,
g) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
h) C(O)R 8 ,
i) NR 8 2 ,
j) halogen, and
said R 6 is substituted by 0 to 13 R 7 groups;
each R 7 is independently selected from the group consisting of:
a) OH,
b) (C 1 -C 12 )alkyl,
c) O—(C 1 -C 12 )alkyl,
d) S—(C 1 -C 12 )alkyl,
e) (CH 2 ) 0-6 -phenyl,
f) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
g) C(O)R 8 ,
h) OC(O)R 8 ,
i) NR 8 2 ,
j) halogen, and
said R 7 is substituted by 0 to 13 R 9 groups;
each R 8 is independently selected from the group consisting of:
a) H,
b) (C 1 -C 12 )alkyl,
c) O—(C 1 -C 12 )alkyl,
d) (C 3 -C 12 )cycloalkyl,
e) (CH 2 ) 0-6 -phenyl,
f) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
g) C(O)R 11 , and
said R 8 is substituted by 0 to 13 R 9 groups;
each R 9 is independently selected from the group consisting of:
a) OH,
b) (C 1 -C 12 )alkyl,
c) O—(C 1 -C 12 )alkyl,
d) (C 3 -C 12 )cycloalkyl,
e) heterocyclyl, where said heterocyclyl group groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
f) C(O)R 11 ,
g) NR 11 2 ,
h) halogen, and
said R 9 is substituted by 0 to 13 R 10 groups;
each R 10 is independently selected from the group consisting of:
a) halogen,
b) ═O, and
c) C(O)R 11 ; and
R 11 is selected from the group consisting of:
a) H, and
b) (C 1 -C 12 )alkyl.
15. The composition according to claim 14 , further comprising a second therapeutic agent.
16. A method of treating a fungal infection in a patient in need thereof, comprising administering to said patient an effective amount of a compound of Formula (I)
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
X is selected from the group consisting of O and H,H;
R 1 is selected from the group consisting of:
a) OH,
b) O—(C 1 -C 12 )alkyl,
c) O—(C 3 -C 8 )cycloalkyl,
d) O-heterocyclyl,
e) OC(O)H,
f) OC(O)—(C 1 -C 12 )alkyl,
g) OC(O)—((C 3 -C 8 )cycloalkyl, and
h) OC(O)-(heterocyclyl),
where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S;
R 2 is selected from the group consisting of:
a) (C 1 -C 12 )alkyl, and
b) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S, and
said R 2 is substituted by 0 to 4 R 4 groups;
R 3 is selected from the group consisting of:
a) CH 2 OH,
b) CH 2 OC(O)(C 1 -C 12 alkyl),
c) COOH,
d) COO(C 1 -C 12 )alkyl, and
e) COO(CH 2 ) 0-6 phenyl;
each R 4 is independently selected from the group consisting of:
a) (C 1 -C 12 )alkyl,
b) (C 3 -C 8 )cycloalkyl,
c) OH,
d) NR 5 2 ,
e) ONR 5 2 ,
f) O(C 1 -C 12 )alkyl,
g) C(O)R 6 ,
h) S(O) 2 R 6 , and
i)
said R 4 is substituted by 0 to 4 R 7 groups;
each R 5 is independently selected from the group consisting of:
a) H,
b) (CH 2 ) 0-12 R 6 ,
c) C(O)R 6 ,
d) S(O) 2 R 6 , and
e)
said R 5 is substituted by 0 to 13 R 7 groups;
each R 6 is independently selected from the group consisting of:
a) H,
b) OH,
c) (C 1 -C 12 )alkyl,
d) O—(C 1 -C 12 )alkyl,
e) (C 3 -C 12 )cycloalkyl,
f) (CH 2 ) 0-6 -phenyl,
g) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
h) C(O)R 8 ,
i) NR 8 2 ,
j) halogen, and
said R 6 is substituted by 0 to 13 R 7 groups;
each R 7 is independently selected from the group consisting of:
a) OH,
b) (C 1 -C 12 )alkyl,
c) O—(C 1 -C 12 )alkyl,
d) S—(C 1 -C 12 )alkyl,
e) (CH 2 ) 0-6 -phenyl,
f) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
g) C(O)R 8 ,
h) OC(O)R 8 ,
i) NR 8 2 ,
j) halogen, and
said R 7 is substituted by 0 to 13 R 9 groups;
each R 8 is independently selected from the group consisting of:
a) H,
b) (C 1 -C 12 )alkyl,
c) O—(C 1 -C 12 )alkyl,
d) (C 3 -C 12 )cycloalkyl,
e) (CH 2 ) 0-6 -phenyl,
f) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
g) C(O)R 11 , and
said R 8 is substituted by 0 to 13 R 9 groups;
each R 9 is independently selected from the group consisting of:
a) OH,
b) (C 1 -C 12 )alkyl,
c) O—(C 1 -C 12 )alkyl,
d) (C 3 -C 12 )cycloalkyl,
e) heterocyclyl, where said heterocyclyl groups are chosen from 5- to 8-membered rings containing from 1 to 4 heteroatoms independently selected from N, O and S,
f) C(O)R 11 ,
g) NR 11 2 ,
h) halogen, and
said R 9 is substituted by 0 to 13 R 10 groups;
each R 10 is independently selected from the group consisting of:
a) halogen,
b) ═O, and
c) C(O)R 11 ; and
R 11 is selected from the group consisting of:
a) H, and
b) (C 1 -C 12 )alkyl.
17. The method according to claim 16 , wherein said fungal infection is caused by Cryptococcus spp., Candida spp. or Aspergillus spp. fungi.