US 2026/0272934 A1 · 1-THIOXO-2,4-DIHYDROTHIENO[2,3-E] [1,2,4]TRIAZOLO[4,3-A]PYRIMIDIN-5(1H)-ONE DERIVATIVES AS ALLOSTERIC INHIBITORS OF THE POLO-LIKE KINASE 1 (PLK1) POLO BOX DOMAIN (PBD) FOR THE TREATMENT OF CANCER

Abstract

Disclosed are allosteric inhibitors of the Plk1 Polo Box Domain (PBD), which are useful in treating cancers by inducing mitotic block of the cancer cells. Examples of such inhibitors include compounds of formula (I) and (II), as well as pharmaceutically acceptable salt thereof, wherein X, R1, R2, and R3 are as defined. Also disclosed are pharmaceutical compositions containing a compound or salt thereof and a method of treating cancer in an animal by administering to the animal an effective amount of the compound or the pharmaceutical composition.

Claims23

Dependent claims

A compound of formula (I), a prodrug of formula (II), or a pharmaceutically acceptable salt thereof,

wherein X is O or S;
R1 is H, halo, C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl C1-C3 alkyl, 4,5-fused phenyl, or 4,5-fused halophenyl;
R2 is halo or C1-C6 alkyl;
and
R3 is C1-C3 alkyl;
or a compound selected from the group consisting of compounds Nad-1 to Nad-8 and CIL-1 to CIL-18:
a compound of formula 22, a compound of formula (A), (B), (C), (D), or (E), or a pharmaceutically acceptable salt thereof:

4 more elements

Dependencies are inferred from the claim text.

Facts

Application

19/168,983Filed 29 Mar 2024

Priority

30 Mar 2023

Published

17 Sep 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings
C07D 491/14
In which the condensed system contains three hetero rings: ortho-condensed systems
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…
A61P 35/00
Antineoplastic agents

1-thioxo-2,4-dihydrothieno[2,3-e] [1,2,4]triazolo[4,3-a]pyrimidin-5(1h)-one derivatives as allosteric inhibitors of the polo-like kinase 1 (plk1) polo box domain (pbd) for the treatment of cancer

Life of this patent

1-thioxo-2,4-dihydrothieno[2,3-e] [1,2,4]triazolo[4,3-a]pyrimidin-5(1h)-one derivatives as allosteric inhibitors of the polo-like kinase 1 (plk1) polo box domain (pbd) for the treatment of cancer

Life of this patent

Abstract

Claims23