| 摘要 |
The present invention relates to an (S)-enantiomer of an aminoheteroaryl compound for use in treating and/or preventing cancer in a subject. The invention further relates to a pharmaceutical composition comprising said compound. Another aspect of the invention is directed to an in vitro method for determining the effectiveness of said (S)-enantiomer of an aminoheteroaryl compound, or said pharmaceutical composition, the method comprising the steps of: (a) obtaining a cell or tissue sample from a subject; and (b) determining the subject's NUDT1/MTH1-status; wherein a NUDT1/MTH1-positive cell or tissue sample is indicative of an effective treatment and/or prevention of cancer. In addition, provided herein is a screening method for identifying a target of an (S)-enantiomer of an aminoheteroaryl compound. Furthermore, in context of this invention, the herein described compounds inhibit the biological activity of MTH1. |
| 主权项 |
1. A method of treatment of cancer in a subject in need of such a treatment, comprising administering to said subject a therapeutically effective amount of an (S)-enantiomer of an aminoheteroaryl compound, wherein the compound has the following chemical structure represented by Formula (1) wherein: R1 is —NH2, —NR2H, —OH or —SH; R2 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; R3 is C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl or cyclopropyl; Y is N or CR4; R4 is hydrogen, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl or C3-6 cycloalkyl; each R5, R6 and R7 is independently fluorine, chlorine, bromine or iodine; R8 is hydrogen or -A-Bn—X, wherein
A is a single bond, —C(═O)— or —C(═O)CH2—;B is C1-4 alkylene, C2-4 alkenylene or —(OCH2CH2)—;n is 0, 1, 2, 3, 4 or 5, andX is —NHR2; —NH2; —SH; —OH or O-alkyl; or a pharmaceutically acceptable salt, solvate or prodrug thereof. |
