1011244-72-6Relevant articles and documents
Rational design, synthesis and biological evaluation of dual PARP-1/2 and TNKS1/2 inhibitors for cancer therapy
Xu, Yizhu,Wu, Huanhuan,Huang, Lei,Zhai, Bingxin,Li, Xiaofei,Xu, Shuaiqi,Wu, Xingxin,Zhu, Qihua,Xu, Qiang
, (2022/05/04)
Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are the first and most successful drugs designed to exploit the concept of synthetic lethality (SL) between PARP-1 and BRCA1/2, which provides a novel strategy for tumor treatment. However, narrowed indications and resistance to PARP-1 inhibitors have hampered their further clinical application. Inducing “BRCAness” by targeting other targets, which will directly or indirectly disturb the homologous recombination (HR) repair pathway of double-strand DNA breaks (DSBs), is a promising strategy for expanding the clinical application of PARP-1 inhibitors and overcoming resistance to these inhibitors. Tankyrase1/2 (TNKS1/2) are involved in the nonhomologous end-joining (NHEJ) DNA repair pathway by regulating Wnt/β-catenin signaling. TNKS1/2 can also induce a “BRCAness” phenotype by regulating Wnt signaling, which increases the sensitivity of tumor cells with BRCA proficiency to PARP-1 inhibitors. These results suggest that cotargeting PARP1/2 and TNKS1/2 not only exerts a synergistic effect in the treatment of tumors but also provides a novel strategy for expanding the clinical application of PARP-1 inhibitors and overcoming resistance to PARP-1 inhibitors. Therefore, a series of dual PARP-1/2 and TNKS1/2 inhibitors were rationally designed, synthesized, and evaluated for their pharmacological properties. Among these candidates, compound I-9 showed excellent inhibitory activity as it inhibited PARP-1/2 and TNKS1/2 with IC50 values of 0.25 nM, 1.2 nM, 13.5 nM and 4.15 nM, respectively. I-9 exhibited favorable synergistic antitumor efficacy in both BRCA-mutant and BRCA-wild-type cancer lines. Moreover, I-9 exerted prominent dose-dependent antitumor activity in an HCT116 cell-derived xenograft model and was significantly more efficacious than olaparib and E7449. Overall, the present study indicated that I-9, a dual PARP-1/2 and TNKS1/2 inhibitor, is a novel and promising agent for cancer therapy.
COMPOUND HAVING BENZAMIDE SKELETON AND CYCLOOXYGENASE (COX-1)-SELECTIVE INHIBITORY ACTIVITY
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Page/Page column 11, (2009/07/10)
This invention provides a novel COX-1-selective inhibitor. This invention relates to a novel compound represented by the formula below or a salt thereof. This invention also relates to an analgesic agent, an antiinflammatory agent, an antitumor agent, an antiplatelet aggregation agent, and a cyclooxygenase-1-selective inhibitor comprising, as an active ingredient, such compound or salt thereof.
Synthesis and Antiviral Activity of Sulfonamidobenzophenone Oximes and Sulfonamidobenzamides
Ogata, Masaru,Matsumoto, Hiroshi,Shimizu, Sumio,Kida, Shiro,Wada, Toru,et al.
, p. 417 - 423 (2007/10/02)
To find antiviral agents, various sulfonamidobenzophenone oximes (II) were synthesized from the appropriate m-sulfonamidobenzophenones by hydroxylamine reaction.The reaction products were generally obtained as syn/anti mixtures which were separable by fractional crystallization.The anti isomer had more potent antipoliovirus activity than the syn isomer.Various sulfonamidobenzamides (III) which were structurally related to II were synthesized by the reaction of amino-substituted benzamides with sulfuryl chloride or amines with (aminosulfonyl)benzoyl chloride.Antiviral activity was examined by the plaque-inhibition test.Compounds 5, 36, and 69 exhibited strong antipicornavirus activity.The structure-activity relationships are discussed.
