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US 10,420,845 B2Granted
Taggable heteroaromatic drugs and conjugates thereof
AssigneeRamot at Tel-Aviv University Ltd.
InventorsDoron Shabat, Ronit Satchi-Fainaro, Samer Gnaim, Anna Scomparin
Life of this patent
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Abstract
The present disclosure provides heteroarene-based drug derivatives having a “clickable” ketone group, as well as conjugates of said drug derivatives with targeting moieties capable of binding to extracellular antigens; and pharmaceutical compositions comprising them.
Claims25
A compound of the formula I:
- Y—CF2—(CR1R2)n—X—(CR1R2)m—R1 I
- wherein
- Y is a drug or a bioactive reagent, comprising a heteroaromatic ring and linked via a carbon atom of said heteroaromatic ring;
- X is carbonyl, or cyclic ketal substituted with 1 to 4 groups each independently is phenyl or naphtyl substituted ortho to the carbon of attachment with —NO2, and optionally further substituted at any position other than ortho to the carbon of attachment with one or more groups each independently selected from the group consisting of —O—(C1-C8), —(C1-C8)alkyl, —N(R′)2, and halogen, wherein R′ each independently is —(C1-C8)alkyl or H;
- R1 and R2 each independently is H, halogen, —OR3, —CO—R3, —CO—OR3, —OCO—OR3, —OCO—N(R3)2, —CN, —NO2, —SR3, —N(R3)2, —CO—N(R3)2, —(C1-C8)alkyl, —(C2-C8)alkenyl, —(C2-C8)alkynyl, (C3-C10)cycloalkyl, (C6-C14)aryl, or 4-12-membered heterocyclyl;
- R3 is H, —(C1-C18)alkyl, —(C2-C18)alkenyl, or —(C2-C18)alkynyl;
- and
- n and m each independently is an integer of 1-8,
- or a pharmaceutically acceptable salt thereof.
6 more elements
A conjugate of the formula II:
- Y is a drug or a bioactive reagent, comprising a heteroaromatic ring and linked via a carbon atom of said heteroarimatic ring;
- R1 and R2 each independently is H, halogen, —OR3, —CO—R3, —CO—OR3, —OCO—OR3, —OCO—N(R3)2, —CN, —NO2, —SR3, —N(R3)2, —CO—N(R3)2, —(C1-C8)alkyl, —(C2-C8)alkenyl, —(C2-C8)alkynyl, (C3-C10)cycloalkyl, (C6-C14)aryl, or 4-12-membered heterocyclyl;
- R3 is H, —(C1-C18)alkyl, —(C2-C18)alkenyl, or —(C2-C18)alkynyl;
- R4 is absent, or is selected from the group consisting of —NH—(CH2)p—, —NH—CO—(CH2)p—, —NH—CO—NH—(CH2)p—, —NH—CO—O—(CH2)p—, —O—(CH2)p—, —O—CO—(CH2)p—, —O—CO—NH—(CH2)p—, and —O—CO—O—(CH2)p—;
- R5 is a polymer-, protein-, peptide-, or carbohydrate moiety;
- R6 is H, —(CH2)y—OH, —(CH2)y—SH, —(CH2)y—NH2, —(CH2)y—COOH, —(CH2)y—SO3H, or a divalent radical selected from the group consisting of —(CH2)y—O—, —(CH2)y—S—, —(CH2)y—NH—, —(CH2)y—OCO— and —(CH2)y—SO3—;
- n and m each independently is an integer of 1-8;
- p and y each independently is an integer of 0-8;
- and
- T is absent, or is a targeting moiety capable of binding to an extracellular antigen and linked via a functional group thereof, provided that when T is absent R6 is not a divalent radical, and when T is a targeting moiety R6 is a divalent radical,
- or a pharmaceutically acceptable salt thereof.
8 more elements
Dependencies are inferred from the claim text.