Design, synthesis, and biological evaluation of quinazolin-4(3H)-one derivatives co-targeting poly(ADP-ribose) polymerase-1 and bromodomain containing protein 4 for breast cancer therapy was written by Chang, Xiaosa;Sun, Dejuan;Shi, Danfeng;Wang, Guan;Chen, Yanmei;Zhang, Kai;Tan, Huidan;Liu, Jie;Liu, Bo;Ouyang, Liang. And the article was included in Acta Pharmaceutica Sinica B in 2021.Computed Properties of C9H12N2O3 This article mentions the following:
This study was aimed to design the first dual-target small-mol. inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors I [R1 = H, 4,6-(OMe)2; R2 = C(O)NH2, C(O)NHMe, etc.], II [R3 = H, 5-OMe, 4,6-(OMe)2; n1 = 0,1], III [R4 = H, 5-OMe, 4,6-(OMe)2; R5 = 4-(cyclopropanecarbonyl)piperazine-1-carbonyl, 3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolyl], IV [R6 = Cl, 3-F, 3-Cl, etc.; R7 = 2-benzamidyl, 1H-benzo[d][1,2,3]triazol-1-yl, 1H-indazol-6-yl, etc.; n2 = 1,2,3,4,5] were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chem. optimization. Among these compounds, IV [R6 = H; R7 = 2-benzamidyl; n2 = 2] was selected and exhibited micromole enzymic potencies against BRD4 and PARP1, resp. Compound IV [R6 = H; R7 = 2-benzamidyl; n2 = 2] was further showed to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound IV [R6 = H; R7 = 2-benzamidyl; n2 = 2] was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound IV [R6 = H; R7 = 2-benzamidyl; n2 = 2] showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer. In the experiment, the researchers used many compounds, for example, 2-Amino-4,6-dimethoxybenzamide (cas: 63920-73-0Computed Properties of C9H12N2O3).
2-Amino-4,6-dimethoxybenzamide (cas: 63920-73-0) belongs to amides. Amides can be viewed as a derivative of a carboxylic acid RC(=O)OH with the hydroxyl group –OH replaced by an amine group −NR′R″; or, equivalently, an acyl (alkanoyl) group RC(=O)− joined to an amine group. Amides can be freed from solvent or water by drying below their melting points. These purifications can also be used for sulfonamides and acid hydrazides.Computed Properties of C9H12N2O3
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics