Novel linker compound and ligand-drug conjugate therefor
AssigneeTrioar, Inc.
InventorsSung Ho WOO, Su Ho PARK, Jong Un CHO, Sang Hyeon YUN, Gyoung Wook MIN, Ok Ku PARK, Hyun Mi LEE
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Abstract
The present invention provides a novel linker compound and a ligand-drug conjugate thereof. This can stably deliver an active ingredient to a target site and rapidly release the active ingredient at the target site, and thus can increase efficacy of the active ingredient and can prevent the active ingredient from causing side effects at locations other than the target location.
Claims38
A linker compound represented by Formula 1 below, or a pharmaceutically acceptable salt thereof:
- wherein
- L1 is a divalent or multivalent linking group;
- k is 0 or 1, and j is 1 to 10;
- A is absent, H or a binding functional group;
- and
- U is a moiety represented by Formula A below:
- wherein
- PL is an active agent linked to L2 or the carbon atom to which the benzene ring and A-(L1)k- are bound, via a heteroatom selected from N, O and S;
- L2 is a self-eliminating linker selected such that cleavage of the bond between L2 and the carbon atom to which the benzene ring and A-(L1)k- are bound promotes cleavage of the bond between L2 and PL;
- W is an optional substituent on the benzene ring;
- one of Z1 and Z3 is selected from the group consisting of NR3, O, S and Se, and the other one of Z1 and Z3 and Z2 are each independently CH or N, and —(V)h, if present, each independently replaces H of NH or CH;
- represents a bond with A-(L1)k-;
- R3 is H or C1-C8 hydrocarbyl;
- V is an electron withdrawing group, an electron donating group, or —CH2-(L2)l-PL-;
- T is a triggering group capable of initiating the release of PL and L2, if present, through a 1,6-elimination reaction upon cleavage;
- L3 is an optional self-immolative spacer group that, if present, is cleaved sequentially upon cleavage of T;
- X and Y are each independently selected from —O—, —NH—, and S;
- and
- h, i, l, x and y are each independently 0 or 1, and p is an integer from 0 to 2.
A linker compound represented by Formula B below, or a pharmaceutically acceptable salt thereof:
- [Formula B]
- wherein
- V′ is —CH2-(L2)l-PL;
- L2 is a self-eliminating linker selected such that cleavage of the bond between the —CH2— of V and L2 promotes cleavage of the bond between L2 and PL;
- PL is an active agent linked to L2 or —CH2— of V′ via a heteroatom selected from N, O and S;
- one of Za and Zb is selected from the group consisting of N, NR3, O, S and Se, the other one of Za and Zb is CH or N;
- R3 is H or C1-C8 hydrocarbyl;
- T is a triggering group capable of initiating the release of PL and L2, if present, through a 1,6-elimination reaction upon cleavage;
- L3 is an optional self-immolative spacer group that, if present, is cleaved sequentially upon cleavage of T;
- X and Y are each independently selected from —O—, —NH—, and S;
- and
- i, l, x and y are each independently 0 or 1, and p is an integer of 0 to 2.
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Dependencies are inferred from the claim text.