Bivalent linkers and conjugates thereof
Bivalent linkers to be included in or for preparing vitamin, drug, diagnostic agent, and/or imaging agent conjugates are described.
1. A compound of the formula
wherein
X 1 is heteroarylthio;
Q is selected from the group consisting of
where R a and R b are each independently hydrogen or alkyl; or R a and R b are taken together with the attached carbon atom to form a carbocyclic ring; m and n are each independently an integer from 1 to about 4; and * represents the point of attachment; and
X 2 is aryloxy.
2. The compound of claim 1 , wherein X 1 is optionally substituted 2-pyridinylthio or optionally substituted 4-pyridinylthio.
3. The compound of claim 1 , wherein X 1 is substituted by at least one electron withdrawing substituent selected from the group consisting of cyano, nitro, alkylsulfonyl, arylsulfonyl, halo, haloalkyl, acyl, and carboxyl.
4. The compound of claim 1 , wherein X 1 is substituted by a nitro group.
5. The compound of claim 1 , wherein X 1 is selected from the group consisting of
where * represents the point of attachment.
6. The compound of claim 1 , wherein X 1 is
where * represents the point of attachment.
7. The compound of claim 1 , wherein X 2 is optionally substituted phenyl.
8. The compound of claim 1 , wherein X 2 is substituted by at least one electron withdrawing substituent selected from the group consisting of cyano, nitro, alkylsulfonyl, arylsulfonyl, halo, haloalkyl, acyl, and carboxyl.
9. The compound of claim 1 , wherein X 2 is substituted by a nitro group.
10. The compound of claim 1 , wherein X 2 is selected from the group consisting of
where * represents the point of attachment.
11. The compound of claim 1 , wherein X 2 is
where * represents the point of attachment.
12. The compound of claim 1 , wherein n is 1.
13. The compound of claim 1 , wherein R a and R b are each independently hydrogen or lower alkyl.
14. The compound of claim 1 , wherein R a and R b are each hydrogen.
15. The compound of claim 1 , wherein R a and R b are taken together with the attached carbon atom to form a carbocyclic ring.
16. The compound of claim 1 , wherein R a and R b are taken together with the attached carbon atom to form cyclopropyl.
17. The compound of claim 1 , wherein Q is
where R a and R b are each independently hydrogen or alkyl; or R a and R b are taken together with the attached carbon atom to form a carbocyclic ring; n is an integer from 1 to about 4; and * represents the point of attachment.
18. The compound of claim 1 , wherein Q is
where m is an integer from 1 to about 4 and * represents the point of attachment.
19. The compound of claim 1 , wherein the compound is of the formula