Small molecule drug conjugates of gemcitabine monophosphate
Disclosed are compounds having formula (1): or a pharmaceutically acceptable salt, ester, amide, solvate, or stereoisomer thereof, wherein L, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 are each as defined in the specification; compositions thereof; uses thereof; and methods of use thereof.
1. A compound having one of the following structures:
Com-
pound
#
Structure
1
2
3
4
5
6
7
8
9
or a pharmaceutically acceptable salt, ester, amide, solvate, or stereoisomer of any one of compounds 1-9.
2. A compound, having formula (Id-ii-1)
or a pharmaceutically acceptable salt, ester, amide, solvate, or stereoisomer thereof
wherein:
Z 3 , Z 4 , and Z 5 are each independently hydrogen, methyl optionally substituted with 1-3 halo, halo, methoxy optionally substituted with 1-3 halo or deuterated methoxy; and
each M 2 is independently selected from the group consisting of OH and O − (M′), wherein (M 1 ) in each occurrence is independently a metal cation, ammonium, an alkyl ammonium cation, or an amino acid cation.
3. The compound of 2 , wherein each of Z 5 and Z 3 is independently methoxy.
4. The compound of 2 , wherein Z 4 is hydrogen.
5. The compound of 2 , wherein the compound is:
or a pharmaceutically acceptable salt, ester, amide, solvate, or stereoisomer thereof.