| 摘要 |
Provided herein are hemiasterlin derivatives, conjugates thereof, compositions comprising the derivatives or conjugates thereof, methods of producing the derivatives and conjugates thereof, and methods of using the derivatives, conjugates, and compositions for the treatment of cell proliferation. The derivatives, conjugates, and compositions are useful in methods of treatment and prevention of cell proliferation and cancer, methods of detection of cell proliferation and cancer, and methods of diagnosis of cell proliferation and cancer. In an embodiment, the hemiasterlin derivatives are according to Formula 1000:;;or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein Ar, L, W1, W4, W5, SG, and R are as described herein. |
| 主权项 |
1. A compound according to Formula 1000:or a pharmaceutically acceptable salt, solvate, stereoisomer, or tautomer thereof, wherein:
Ar is a divalent five- or six-membered, substituted or unsubstituted, monocyclic aryl or heteroaryl ring or a divalent eight-, nine- or ten-membered, substituted or unsubstituted, fused bicyclic aryl or heteroaryl ring; L is absent or —CH2—; W1, W2, W3, W4, W5 are each independently a single bond, absent, or a divalent attaching group; EG is absent or an eliminator group; each RT is a release trigger group, in the backbone of Formula 1000 or bonded to EG, wherein each RT is optional; RT1 is a release trigger group, or a cleavable linker, or RT1 is absent; HP is a single bond, absent, or a divalent hydrophilic group; HP1 is a single bond, absent, a divalent hydrophilic group, orwhere RHP is a monovalent hydrophilic group;
SG is a single bond, absent, or a divalent spacer group; andR is hydrogen, a terminal conjugating group, or a divalent residue of a terminal conjugating group;or, in the alternative, W1, W2, W3, W4, W5, EG, RT, HP, SG, and R combine to form —H. |
