Shi, Wei; Zhang, Ping; Zou, Feng; Zhou, Jiaqi; Yin, Ziyu; Cai, Zilong; Ghaleb, Hesham; Jiang, Yuxuan; Huang, Wenlong; Liu, Yan; Qiu, Qianqian; Qian, Hai published the artcile< Exploration of novel phthalazinone derivatives as potential efflux transporter inhibitors for reversing multidrug resistance and improving the oral absorption of paclitaxel>, Electric Literature of 3731-53-1, the main research area is phthalazinone preparation antitumor efflux transporter inhibitor SAR pharmacokinetic; BCRP; Efflux transporter; Multidrug resistance; Oral bioavailability; P-gp.
A series of phthalazinone ring derivatives, I [R = 4-pyridylmethylamino, 2-phenylethylamino, 4-(2-morpholinoethyl)anilino, etc.] with different aromatic heterocycles substituents on the amide bond were designed and synthesized for dual inhibition of P-gp and BCRP. Most target compoundsI significantly increased the accumulation of P-gp substrates in the chemo-resistant cancer cell lines by inhibiting the efflux of transporters. Compound I [R = 4-(2-morpholinoethyl)anilino] in particular showed stronger MDR reversal compared to Gefitinib and Verapamil, and comparable to that of the BCRP inhibitor Ko143. In addition, compound I [R = 4-(2-morpholinoethyl)anilino] improved intestinal absorption of paclitaxel (PTX) and enhanced the bioavailability of the orally administered drug in vivo.
European Journal of Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 3731-53-1 belongs to class pyridine-derivatives, and the molecular formula is C6H8N2, Electric Literature of 3731-53-1.